An orthopaedic implant

Abstract

The present invention relates to a 3D-printed orthopaedic implant (201, 301, 401) comprising a non-porous support portion (205, 305, 405) and a porous osteoconductive scaffold (203, 303, 403), wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D-printed orthopaedic implant, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel (207a-e, 307a-c, 407a-c) extending into the osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament (101a, b) therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width. A solid osteoinductive filament operable to be introduced into the 3D-printed orthopaedic implant, and a kit formed therefrom, are also encompassed.

Description

[0001] AN ORTHOPAEDIC IMPLANT

[0002] FIELD OF INVENTION

[0003] The present invention relates to an orthopaedic implant that facilitates enhanced bone healing through bone formation and / or bone fusion.

[0004] BACKGROUND

[0005] Bone healing is a complex biological process involving the regeneration and remodelling of bone tissue. Bone healing procedures, for example spinal fusion surgeries, commonly employ implantable orthopaedic devices incorporating graft material to stabilise the bone and promote bone growth. The effectiveness of these implants depends on three primary biological mechanisms: osteoconduction (the ability of a material to serve as a scaffold that supports the attachment, migration, and growth of new bone-forming cells), osteoinduction (the recruitment and stimulation of progenitor cells to differentiate into osteoblasts, which are responsible for new bone formation. This process is often mediated by signalling molecules such as Bone Morphogenetic Proteins (BMPs)), and osteogenesis (the direct formation of new bone by osteoblasts, either from transplanted viable cells within the graft material or from the patient's own bone-forming cells). These mechanisms and their interplay are key to achieving optimised bone healing.

[0006] Historically, implants facilitating the regeneration and remodelling of bone tissue have been solid structures comprising central bone graft chambers that extend completely through the implant and house bone graft materials. The graft materials guide and stimulate cell activity to facilitate bone growth within the confined space of the central graft chamber. In contrast, the solid structure of the implant does not participate in bone formation, instead providing only mechanical and load-bearing stability during the healing process.

[0007] Recent advancement of 3D-printing has improved implantable orthopaedic devices by enabling the production of implants having porous regions. These porous regions are osteoconductive, allowing osteoblasts to infiltrate and proliferate within the structure and providing additional surface area for bonegrowth and integration outside of the central graft chamber. However, to compensate for the introduction of the porous regions, the central bone graft chambers of the implants have had to be reduced to maintain overall strength, resulting in reduced and insufficient bone healing. Furthermore, the optimal sizing of the pores to support osteoconduction is either too small and / or creates inaccessibility, which precludes the uniform distribution of bone grant materials, such as known putty-like osteoinductive-particle containing bone graft materials, throughout the implant. To maintain safety and efficacy of these bone graft materials, they are required to contain particles large enough (typically > 1mm) to resist migration, and this size exceeds the optimal pore size of the osteoconductive elements of the 3D-printed implant. Smaller bone graft particles also risk producing a macrophage response of phagocytosis.

[0008] There is therefore a need to provide improved orthopaedic implants that harness both osteoconductive and osteoinductive principles to facilitate enhanced bone healing.

[0009] SUMMARY OF INVENTION

[0010] According to a first aspect of the present invention, there is provided a 3D-printed orthopaedic implant comprising a non-porous support portion and a porous osteoconductive scaffold, wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D-printed orthopaedic implant, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width.

[0011] According to a second aspect of the present invention, there is provided a 3D-printed orthopaedic implant comprising a porous osteoconductive scaffold and an optional non-porous support portion, wherein the 3D-printed orthopaedic implanthas a porosity of at least 60%, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width.

[0012] According to a third aspect of the present invention, there is provided a solid osteoinductive filament operable to be inserted into a discrete hollow tunnel of a 3D-printed orthopaedic implant, wherein the solid osteoinductive filament has a length of at least three times its width and comprises an osteoinductive agent.

[0013] According to a fourth aspect of the present invention, there is provided a kit for providing a 3D-printed orthopaedic implant, the kit comprising:

[0014] (i) a 3D-printed orthopaedic implant comprising a non-porous support portion and a porous osteoconductive scaffold, wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D- printed orthopaedic implant, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width; and

[0015] (ii) at least one solid osteoinductive filament operable to be inserted into a discrete hollow tunnel of a 3D-printed orthopaedic implant, wherein each solid osteoinductive filament has a length of at least three times its width and comprises an osteoinductive agent.According to a fifth aspect of the present invention, there is provided a kit for providing a 3D-printed orthopaedic implant, the kit comprising:

[0016] (i) a 3D-printed orthopaedic implant comprising a porous osteoconductive scaffold and an optional non-porous support portion, wherein the 3D- printed orthopaedic implant has a porosity of at least 60%, and the 3D- printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width; and

[0017] (ii) at least one solid osteoinductive filament operable to be inserted into a discrete hollow tunnel of a 3D-printed orthopaedic implant, wherein each solid osteoinductive filament has a length of at least three times its width and comprises an osteoinductive agent.

[0018] According to a sixth aspect of the present invention, there is provided a 3D-printed orthopaedic implant comprising a non-porous support portion and a porous osteoconductive scaffold, wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D-printed orthopaedic implant, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the osteoconductive scaffold, wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width, and wherein at least one discrete hollow tunnel contains a solid osteoinductive filament, the solid osteoinductive filament having a length of at least three times its width and comprising an osteoinductive agent.

[0019] According to a seventh aspect of the present invention, there is provided a 3D-printed orthopaedic implant comprising a porous osteoconductive scaffold and anoptional non-porous support portion, wherein the 3D-printed orthopaedic implant has a porosity of at least 60%, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the osteoconductive scaffold, wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform crosssection; and a length that is at least three times greater than its width, and wherein at least one discrete hollow tunnel contains a solid osteoinductive filament, the solid osteoinductive filament having a length of at least three times its width and comprising an osteoinductive agent.

[0020] According to an eighth aspect of the present invention, there is provided a method of promoting bone fusion and / or bone formation, using the 3D-printed orthopaedic implant of the first or second aspect of the present invention and at least one solid osteoinductive filament of the third aspect of the present invention, or the kit according to the fourth or fifth aspect of the present invention, the method comprising:

[0021] (i) inserting a solid osteoinductive filament into at least one discrete hollow tunnel of the 3D-printed orthopaedic implant; and

[0022] (ii) implanting the 3D-printed orthopaedic implant into the body of a subject in need, preferably positioning the 3D-printed orthopaedic implant in a space between two bones or areas of bone, more preferably placing the 3D- printed orthopaedic implant into an intervertebral space between two spinal vertebrae.

[0023] According to a ninth aspect of the present invention, there is provided a method of promoting bone fusion and / or bone formation, using the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, the method comprising:

[0024] (i) implanting the 3D-printed orthopaedic implant into the body of a subject in need, preferably positioning the 3D-printed orthopaedic implant in a spacebetween two bones or areas of bone, more preferably placing the 3D- printed orthopaedic implant into an intervertebral space between two spinal vertebrae.

[0025] According to a tenth aspect of the present invention, there is provided a solid osteoinductive filament according to the third aspect of the present invention, for use as a medicament.

[0026] According to an eleventh aspect of the present invention, there is provided a solid osteoinductive filament according to the third aspect of the present invention, for use in the promotion of bone formation and / or bone fusion.

[0027] According to a twelfth aspect of the present invention, there is provided a kit according to the fourth or fifth aspect of the present invention, for use as a medicament, wherein the porous osteoconductive scaffold is formed of a resorbable material, preferably selected from: resorbable polymers or combinations thereof; and resorbable metals or combinations thereof; or combinations thereof.

[0028] According to a thirteenth aspect of the present invention there is provided a kit according to the fourth or fifth aspect of the present invention, for use in the promotion of bone formation and / or bone fusion, wherein the porous osteoconductive scaffold is formed of a resorbable material, preferably selected from: resorbable polymers or combinations thereof; and resorbable metals, or combinations thereof; or combinations thereof.

[0029] According to a fourteenth aspect of the present invention, there is provided a 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, for use as a medicament, wherein the porous osteoconductive scaffold is formed of a resorbable material, preferably selected from: resorbable polymers or combinations thereof; and resorbable metals or combinations thereof; or combinations thereof.According to a fifteenth aspect of the present invention there is provided a 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, for use in the promotion of bone formation and / or bone fusion, wherein the porous osteoconductive scaffold is formed of a resorbable material, preferably selected from: resorbable polymers or combinations thereof; and resorbable metals, or combinations thereof; or combinations thereof.

[0030] BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 shows solid osteoinductive filaments according to the third aspect of the present invention.

[0032] Figures 2 to 7 show the 3D-printed orthopaedic implants according to the first or second aspect of the present invention.

[0033] DETAILED DESCRIPTION

[0034] The present invention advantageously provides a 3D-printed orthopaedic implant capable of providing localised delivery of osteoinductive material within an osteoconductive scaffold to facilitate enhanced bone healing. The 3D-printed orthopaedic implant enables precise delivery of agents promoting osteoinduction throughout the implant, maximising the recruitment and differentiation of cells therethrough. By facilitating and upregulating (through osteoinduction) bone growth within the porous osteoconductive scaffold of the 3D-printed orthopaedic implant and surrounding tissue, the present invention creates a more interconnected bone structure, improving stability and reducing time to achieve fusion.

[0035] By combining osteoconduction and osteoinduction mechanisms across the totality of the 3D-printed orthopaedic implant, bone healing potential can be enhanced and maximised, whilst minimising limitations associated with any previous approaches. Missing bone can be replaced across the implant structure.

[0036] The incorporation of at least one discrete hollow tunnel into the 3D-printed orthopaedic implant enables targeted delivery of osteoinductive material within anosteoconductive scaffold created by 3D-pri nti ng . This has been achieved through the development, by the present inventors, of solid osteoinductive filaments that can be easily inserted and easily retained within the implants in the hollow tunnels during implantation into the subject in need. Such single solid dosage forms of osteoinductive agents are advantageous over, for example, the use of any liquid form of osteoinductive material which would extrude beyond the intended site, as well as any putty-like osteoinductive agent, which have particle sizes too large (typically > 1mm) to be compatible with osteoconductive porous regions or to achieve uniform application. Furthermore, the singular osteoinductive agent dosage forms of the present invention are much easier to use than putty-like osteoinductive substances that require additional preparation steps at the point of use. The solid filaments are easily retained in the 3D-printed orthopaedic implant throughout its implantation without requiring any further securing means.

[0037] Furthermore, the solid osteoinductive filaments described herein do not comprise any biological substance, such a bone tissue, harvested from an independent donor subject. Accordingly, they do not bear the risk of disease transmission inherent when using human donor tissue. The use of the solid osteoinductive filaments of the present invention also advantageously removes the requirement for a second surgical site to harvest donor bone from the patient, or another subject, which is associated with significant morbidity at the harvest site. The solid osteoinductive filaments of the present invention are able to provide for clinically relevant doses of osteoinductive agent in humans, typically more than 0.2mg / mL of graft material, which is a 1,000 greater dose of osteoinductive agent than is available in, for example, demineralised bone matrix (DBM) products.

[0038] The structure of the 3D-printed orthopaedic implant and the solid nature of the osteoinductive filaments of the present invention advantageously enables more uniform distribution of osteoinductive agent throughout an osteoconductive implant. Not only does this provide enhanced treatment and bone healing, but the overall amount of osteoinductive agent required can be reduced, lowering costs and lessening the risk of side effects associated with excessive osteoinductive agent delivery to a subject. Furthermore, production of the implants by 3D-printingallows for low-cost production and precise control over the placement, dimensions, and / or distribution of the hollow tunnels within the implant, allowing the design to be tailored towards specific patient needs and anatomical considerations.

[0039] Still further, integration of the solid osteoinductive filaments into 3D-printed orthopaedic implants as described herein can reduce, and even eliminate, the role of the central graft chamber, especially for spinal fusion procedures. Although, the implants of the present invention may include a central graft chamber extending completely through the implant, this is no longer a requirement. By combining a porous osteoconductive scaffold within which precise delivery of osteoinductive agents can be achieved, the requirement for a central bone graft chamber can be overcome. This allows for larger and more uniform bone growth and implantation across the whole of the implant structure.

[0040] This is particularly advantageous in procedures such as spinal fusion surgery. These procedures involve inserting the implant between vertebrae in place of the normal intervertebral disc. Vertebrae have an apophyseal ring surrounding softer cortical bone within. Previously, the bone graft material housed in the central graft chamber interacted solely with the softer cortical bone of the vertebrae due to its positioning towards the centre of the implant. However, the discrete hollow tunnels of the present implant means that graft material is not confined to the central graft chamber, but osteoinductive graft material can be distributed throughout the implant, and the hollow tunnels positioned so as to increase interaction of the osteoinductive material with the apophyseal ring, advantageously enabling stronger bone formation and fusion, and reducing the risk of implant subsidence into the vertebral bone. This is a clear example of the advantages of the present invention in allowing the design of the implant to be tailored towards specific patient needs and anatomical considerations. The 3D-printed orthopaedic implant may be custom-made for a specific patient, based on their exact anatomic requirements. The use of pre-operative planning software, such as CT-scans may be used to design the implant, including the location of the discrete hollow tunnels, prior to 3D-printing. The development of the solidosteoinductive filaments allows discrete hollow tunnels to be provided wherever needed across the 3D-printed implant, with simple insertion of filaments therein achieving improved, and in indeed tailored, distribution of osteoinductive material.

[0041] All features of the first to fifteenth aspects of the present invention, including all preferred and optional features detailed below, are applicable to all of the other of the first to fifteenth aspects described herein, and vice versa.

[0042] The 3D-printed orthopaedic implant according to the first aspect of the present invention comprises a non-porous support portion. The 3D-printed orthopaedic implant according to the second aspect of the present invention may comprise a non-porous support portion. Preferably, the 3D-printed orthopaedic implant according to the second aspect of the present invention comprises a non-porous support portion, as defined herein.

[0043] The non-porous support portion may provide mechanical rigidity and load-bearing stability to the implant when in use and positioned within the body of a subject. For example, when the implant is positioned between vertebra in spinal fusion procedures, the non-porous support portion prevents compaction of the implant.

[0044] The non-porous support portion may also have a functional purpose of enabling the 3D-printed orthopaedic implant to be implanted into the body of a subject. The non-porous support portion may comprise means, such as a shallow bore or recess, for interacting with an implantation tool and / or an attachment member such as a screw and / or another associated device needed to aid implantation or secure the implant within the subject.

[0045] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may comprise one or more non-porous support portions. The one or more non-porous support portions may be connected or separate.

[0046] By ‘non-porous’ is meant does not comprise pores. The non-porous support portion does not comprise pores. The non-porous support portion is preferably formed of a continuous phase of solid material. The non-porous support portion is a non-porous solid material.Typically, the non-porous support portion may be present on, or form at part of, the exterior of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. The non-porous support portion may surround or cover at least a portion of the porous osteoconductive scaffold. The non-porous support portion may form at least a portion of an exterior surface of the implant. The non-porous support portion may form an exterior surface of the implant. If the non-porous support portion forms at least a portion of an exterior surface, the non-porous support portion may comprise a window or opening through which the porous osteoconductive scaffold is visible and accessible. The non-porous support portion may form an outer shell around at least a portion of the porous osteoconductive scaffold. The outer or exterior shell preferably does not completely encase the porous osteoconductive scaffold. The non-porous support portion may be positioned at one or more end of the implant. The non-porous support portion may form endplates of the implant. The non-porous support may form a wall(s) around the porous osteoconductive scaffold. The non-porous support may form a cage or cage-like structure around the porous osteoconductive scaffold. The porous osteoconductive scaffold preferably remains visible and accessible.

[0047] An exterior surface of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may comprise the non-porous support portion and / or the porous osteoconductive scaffold. The porous osteoconductive scaffold is preferably accessible and visible from the exterior of the implant. Preferably, at least one exterior surface comprises the porous osteoconductive scaffold, or may be completely formed therefrom. Preferably at least two exterior surfaces comprise the porous osteoconductive scaffold, or may be completely formed therefrom.

[0048] The non-porous support portion may form 20% or less of the total external surface area of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, preferably 15% or less of the total external surface area, more preferably 12% or less, such as 10% or less of the total external surface area of the 3D-printed orthopaedic implant. This may be measured visually, or bymicro-CT imaging, as described herein. The non-porous support portion may form from 0.5% to 20% of the total external surface area of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, preferably from 0.5% to 15%, or from 0.5% to 12%, or from 0.5% to 10% of the total external surface area of the 3D-printed orthopaedic implant. This may be measured visually, or by micro-CT imaging, as described herein. The percentage of the total external surface area formed by the non-porous support portion refers to the external surface area of the 3D-printed orthopaedic implant occupied by the non-porous support portion, and excludes any external surface area occupied by the porous osteoconductive scaffold and at least one discrete hollow tunnel, and optional central graft chamber, as described herein.

[0049] For the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the non-porous support portion may form 20% or less of the volume of the 3D-printed orthopaedic implant, such as 15% or less, or 12% or less, or even 10% or less. For the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the non-porous support portion may form from 0.5% to 20% of the volume of the 3D-printed orthopaedic implant, such as from 0.5% to 15%, or from 0.5% to 12%, or even from 0.5% to 10%. The volume can be measured visually, or by micro-CT imaging, as described herein. The percentage of the implant volume formed by the non-porous support refers to the volume of the 3D-printed orthopaedic implant occupied by the non-porous support portion, and excludes any volume occupied by the porous osteoconductive scaffold and at least one discrete hollow tunnel, and optional central graft chamber, as described herein.

[0050] For the 3D-printed orthopaedic implant according to the first aspect of the present invention, the porous osteoconductive scaffold forms at least 60% of the volume of the 3D-printed orthopaedic implant. For the 3D-printed orthopaedic implant according to the second aspect of the present invention, the porous osteoconductive scaffold may form at least 60% of the volume of the 3D-printed orthopaedic implant. The volume can be measured visually, or by micro-CT imaging, as defined herein. The percentage of the implant volume formed by theporous osteoconductive scaffold refers to the volume of the 3D-printed orthopaedic implant occupied by the porous osteoconductive scaffold including pores of the scaffold, and excludes any volume occupied by the at least one discrete hollow tunnel, and (optional) non-porous support portion and optional central graft chamber, as described herein.

[0051] Preferably, for 3D-printed orthopaedic implants according to the first or second aspect of the present invention, the porous osteoconductive scaffold forms at least 70% of the volume of the 3D-printed orthopaedic implant, such as at least 75%, or at least 80%, and more preferably at least 90% of the volume of the implant. The volume can be measured visually, or by micro-CT imaging, as defined herein.

[0052] For the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the porous osteoconductive scaffold may form from 60% to 98% of the volume of the 3D-printed orthopaedic implant. The volume can be measured visually, or by micro-CT imaging, as defined herein. For 3D-printed orthopaedic implants according to the first or second aspect of the present invention, the porous osteoconductive scaffold may form from 70% to 98% of the volume of the 3D-printed orthopaedic implant, such as from 75% to 98%, or from 80% to 98%, and more preferably from 90% to 98% of the volume of the implant. The volume can be measured visually, or by micro-CT imaging, as defined herein.

[0053] The 3D-printed orthopaedic implant according to the second aspect of the present invention, has a porosity of at least 60%. The 3D-printed orthopaedic implant according to the first aspect of the present invention, may have a porosity of at least 60%. By porosity is meant the amount of ‘empty space’ or ‘negative space’ in the implant. This includes the pores of the porous osteoconductive scaffold as well as the at least one discrete hollow tunnel, and optional central graft chamber. The porosity can be measured as defined herein.

[0054] Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention has a porosity of at least 70%, such as at least 75%, or at least 80% or at least 90% of the 3D-printed orthopaedic implant. The porosity can be measured as defined herein.The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may have a porosity of from 60% to 95%. The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may have a porosity of from 70% to 95%, such as from 75% to 95%, or from 80% to 95%, or from 90% to 95% of the 3D-printed orthopaedic implant. The porosity can be measured as defined herein.

[0055] The 3D-printed orthopaedic implant of the first or second aspect of the present invention may have any suitable size. The 3D-printed orthopaedic implant may have any suitable shape and / or dimensions. As described herein, this not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application. Suitable sizes and / or dimensions for 3D-printed orthopaedic implants for different application in the body are known in the art. The 3D-printed orthopaedic implant may have any suitable height, depth or width. The 3D-printed orthopaedic implant may have a height of from 0.5 mm to 30 mm, such as from 1 mm to 20 mm, or from 2 mm to 15 mm, or from 3 mm to 10 mm. The 3D-printed orthopaedic implant may have a depth of from 3 mm to 70 mm, such as from 5 mm to 65 mm, or from 10 mm to 60 mm. The 3D-printed orthopaedic implant may have a width of from 1 mm to 60 mm, or from 2 mm to 50 mm, such as from 5 mm to 45 mm. For example, a lumbar interbody implant may have a height of from 7 mm to 20 mm, a depth of from 20 mm-55 mm and a width of from 8 mm to 40 mm, and a cervical interbody implant may have a height of from 3 mm to 9 mm, a depth of from 12 mm to 20 mm and a width of from 14 mm to 22 mm, whilst implants for use in dental or craniomaxillofacial will typically be smaller and preferably will have sizes to match the bony void intended to be repaired in that patient. The width, height, and depth of the implant may be measured visually using a measuring instrument such as a ruler or tape, or by micro-CT imaging, as described herein.

[0056] As referred to herein, the height of the implant refers to the average (mean) distance from top (superior - closer to head) to bottom (inferior - closer to feet) of the implant as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures. The average accounts for differinglordotic angles, where the implant is lower at the front and higher at the back, for example, when the implant is used in spinal fusion procedures. As referred to herein, the depth of the implant refers to the distance from front (of subject) to back (of subject) of the implant as it is typically positioned when in use in a subject, for example, in spinal implant and / or procedures. Where the implant is circular or substantially circular, the depth may be the diameter. Where the implant is irregular in shape, the depth refers to the largest value that can be measured for the depth of the implant. As referred to herein, the width of the implant refers to the distance from side to side (laterally) of the implant as it is typically positioned when in use in a subject, for example, in spinal implant and / or fusion procedures. Where the implant is circular or substantially circular, the width may be the diameter. Where the implant is irregular in shape, the width refers to the largest value (widest) that can be measured for the width of the implant. The height, width or depth refers to a continuous dimension.

[0057] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may comprise any suitable number of exterior surfaces. Preferably, the 3D-printed orthopaedic implant comprises three or more exterior surfaces, such as four or more.

[0058] The term ‘osteoconductive’ and like terms used herein has the same meaning as known in the art, referring to the ability of a material to serve as a scaffold that facilitates the growth of new bone along its surface(s). Osteoconductive materials, such as the porous osteoconductive scaffold described herein, are operable to provide a physical structure for osteoblasts and endothelial cells to migrate, proliferate, and form new bone.

[0059] The term ‘porous’ as used herein has the same meaning as known in the art, and refers to a material having minute spaces or holes (pores) through which liquid or air may pass.

[0060] The porous osteoconductive scaffold comprises pores.The porous osteoconductive scaffold of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may be microporous, macroporous, nanoporous, or mesoporous, or any combination thereof. The porous osteoconductive scaffold may contain micropores, macropores, nanopores, or mesopores, or any combination thereof. Preferably, the porous osteoconductive scaffold contains at least micropores and nanopores, more preferably at least micropores. The porous osteoconductive scaffold may consist of micropores and nanopores, or may consist of micropores.

[0061] The terms ‘microporous’, ‘macroporous’, ‘nanoporous’ and ‘mesoporous’ as used herein, have the same meaning as commonly understood in the art. A microporous structure contains micropores. A macroporous structure contains macropores. A nanoporous structure contains nanopores. A mesoporous structure contains mesopores. Micropores may have a pore size of 20 pm or less. Nanopores may have a pore size of less than 1 pm. Macropores may have a pore size of from 100 pm to 2 mm. Mesopores may have a pore size of from 20 pm to 100 pm. Pore size may refer to pore diameter.

[0062] Preferably, the porous osteoconductive scaffold contains pores of a pore size of from 20 pm to 1 mm, such as from 100 to 900 pm, preferably from 200 pm and 800 pm, more preferably from 300 pm to 700 pm. The pores of the porous osteoconductive scaffold may consist of pores of a pore size of from 20 pm to 1 mm, such as from 100 to 900 pm, preferably from 200 pm and 800 pm, more preferably from 300 pm to 700 pm. Pore size may be measured as defined herein.

[0063] The porous osteoconductive scaffold may have any suitable structure. The porous osteoconductive scaffold may have a structure selected from, but not limited to: a mesh, lattice, web, strut, weave, honeycomb structure, simple cubic structure, tetrahedral structure, diamond structure, or combinations thereof. The pores of the porous osteoconductive scaffold can be fabricated as desired by 3D-printing with respect to both pore size and structure.Two or more of the pores of the porous osteoconductive scaffold may be connected. This advantageously enhances the migration of cells and nutrients therethrough and supports the formation of blood vessels.

[0064] Preferably, the centre of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is formed from the porous osteoconductive scaffold. Preferably, the centre of an exterior surface of the 3D-printed orthopaedic implant according to first or second aspect of the present invention is formed of the porous osteoconductive scaffold.

[0065] The porous osteoconductive scaffold may form 80% or more of the total external surface area of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, preferably 85% or more of the total external surface area, more preferably 88% or more, or 90% or more of the total external surface area of the 3D-printed orthopaedic implant. This may be measured visually, or by micro-CT imaging, as described herein. The porous osteoconductive scaffold may form from 80% to 99.5% of the total external surface area of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, preferably 85% to 99.5%, such as 88% to 99.5%, or 90% to 99.5% of the total external surface area of the 3D-printed orthopaedic implant. This may be measured visually, or by micro-CT imaging, as described herein. The percentage of the total external surface area formed by the porous osteoconductive scaffold refers to the external surface area of the 3D-printed orthopaedic implant occupied by the porous osteoconductive scaffold including pores of the scaffold, and excludes any external surface area occupied by the at least one discrete hollow tunnel, and (optional) non-porous support portion and optional central graft chamber, as described herein.

[0066] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may further comprise a central graft chamber. By a ‘central graft chamber’ as defined herein is meant a hollow tunnel that extends completely though the 3D-printed orthopaedic implant and has a volume of 30% or more, such as 40% or more, of the volume of the implant. The central graft chamber may have a volume of from 30% to 70% of the volume of the implant, such asfrom 40% to 70%. The central graft chamber extends from one exterior surface of the implant to another. Typically, the central graft chamber extends from top to bottom (superior to inferior) completely through the implant as it is typically positioned when in use in a subject. Typically, the central graft chamber extends vertically completely through the implant as it is typically positioned when in use in a subject. Typically, the central graft chamber extends from top to bottom (superior to inferior) completely through the centre of the implant as it is typically positioned when in use in a subject. As described herein, the volume of the central graft chamber of the implant may be measured visually, or by micro-CT imaging, as described herein. The volume of the central graft chamber refers to the volume of the empty space (‘negative’ space) formed by the central graft chamber within the implant, when not filled with graft material.

[0067] The term ‘extends completely through’ as used herein in reference to the 3D-printed orthopaedic implant according to the first or second aspect of the present invention refer to the hollow tunnel extending from one exterior surface of the implant to another. The hollow having two openings, one on each exterior surface, preferably on opposing exterior surfaces of an implant.

[0068] When present, in use, the central graft chamber may be filled with autologous bone, allograft bone, ceramic bone graft substitutes, demineralised bone, cellular grafts, growth factor materials or other materials to promote bone growth.

[0069] Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention does not comprise a central graft chamber. Accordingly, the implant preferably does not comprise a hollow tunnel that extends completely though the implant and has a volume of 30% or more, such as 40% or more, of the implant. The implant preferably does not comprise a hollow tunnel that extends completely through the implant and has a volume of from 30% to 70%, such as from 40% to 70%, of the implant.

[0070] The porous osteoconductive scaffold may be present in every quartile (quarter) of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. Preferably, the porous osteoconductive scaffold is present inevery quintile (fifth), such as every octile (eighth), or more preferably every decile (tenth) ofthe3D-printed orthopaedic implant. The quartile, quintile, octile or decile refer to a portion (quarter, fifth, eighth, or tenth respectively) of the 3D-printed orthopaedic implant. The ‘quartile, ‘quintile’, ‘octile’ or ‘decile’ refer to any continuous portion of the implant. It will be appreciated that if the porous osteoconductive scaffold is present in every quartile, quintile, octile or decile of the implant, it will not comprise a central graft chamber. This may be determined visually, or by micro-CT imaging, as defined herein.

[0071] The porous osteoconductive scaffold may be present throughout the 3D-printed orthopaedic implant. The porous osteoconductive scaffold may be distributed throughout the 3D-printed orthopaedic implant.

[0072] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold. As described herein, this advantageously enables an individual solid osteoinductive filament(s) of the present invention to be introduced into the porous osteoconductive scaffold to facilitate enhanced bone healing.

[0073] By the term ‘discrete’ as used herein in the context of each hollow tunnel of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is meant that each tunnel does not intersect with any other hollow tunnel (or optional central graft chamber) present in the implant. Each hollow tunnel is a distinct, individual entity with respect to any other hollow tunnel (or optional central graft chamber).

[0074] Each discrete hollow tunnel is a continuous structure. By this is meant that it preferably forms an uninterrupted space extending into, or completely through, the implant. Each discrete hollow tunnel preferably forms a space that extends into, or completely through, the implant, without interruption.

[0075] Each discrete hollow tunnel comprises an opening on an exterior surface of the 3D-printed orthopaedic implant according to the first or second aspect of thepresent invention. The opening enables the discrete hollow tunnel to be operable for insertion of a solid osteoinductive filament. An opening of the discrete hollow tunnel may be on the porous osteoconductive scaffold or may be on a non-porous support portion. A discrete hollow tunnel may have one or two openings on an exterior surface(s) of the implant, preferably on different exterior surfaces of the implant. If a discrete hollow tunnel extends completely through the implant, the discrete hollow extends from one exterior surface to another and has two openings, one on each exterior surface, and preferably on opposing exterior surfaces. Preferably, a discrete hollow tunnel has a single opening.

[0076] Each discrete hollow tunnel has a substantially uniform cross-section. By this is meant that the cross-section is substantially continuous (substantially the same) throughout the length of hollow tunnel. It is substantially uniform in shape and size throughout the length of the hollow tunnel. This is in contrast to a pore, or connected pores, of the porous osteoconductive scaffold. It is also in contrast to a threaded opening, for example for a screw. A discrete hollow tunnel is preferably non-threaded. By ‘substantially’ when referring to the uniform cross-section is meant that the cross-section of the discrete hollow tunnel is principally the same throughout its length, but may have small deviations therefrom either caused by the 3D-printing process, and / or by the porous nature of the porous osteoconductive scaffold through which it extends. This may be determined visually, or by micro-CT imaging as described herein. Each discrete hollow tunnel may have a uniform cross-section (a cross-section that is uniform in shape and size throughout the length of the hollow tunnel, i.e. of the same shape and size throughout its length) if there are no small deviations either caused by the 3D-printing process and / or by the porous nature of the porous osteoconductive scaffold.

[0077] The discrete hollow tunnel(s) may be distributed throughout the 3D-printed orthopaedic implant according to the first or second aspect of the present invention in any configuration. When the implant comprises at least two discrete hollow tunnels, the discrete hollow tunnels may be distributed throughout the osteoconductive scaffold. As described herein, the positioning and dimensions ofthe hollow tunnels(s) not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application.

[0078] The term ‘distributed throughout’ and like terms as used herein in reference to the position of the discrete hollow tunnels within the 3D-printed orthopaedic implant according to the first or second aspect of the present invention preferably refers to a uniform distribution of the discrete hollow tunnels across the implant. Preferably, when the discrete hollow tunnels are distributed throughout the implant, no discrete hollow tunnel extends into the implant from top (superior -closer to head) to bottom (inferior - closer to feet) of the implant as it is typically positioned when in use in a subject (for example, in spinal implant and / or fusion procedures), and at a 90° angle to an exterior surface.

[0079] An opening of at least one discrete hollow tunnel, preferably two or more, such as three or more, more preferably each discrete hollow tunnel, may be independently positioned towards or at the periphery of an exterior surface of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. An opening of at least one discrete hollow tunnel, preferably two or more, such as three or more, more preferably each discrete hollow tunnel, may be independently positioned around the periphery of an exterior surface of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. The exterior surface is preferably a top (superior) or bottom (inferior) exterior surface of the implant as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.

[0080] Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention does not comprise a discrete hollow tunnel extending completely through the centre of the implant at a 90° angle to an exterior surface and from top (superior - closer to head) to bottom (inferior - closer to feet) of the implant as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures. Preferably, an opening of a discrete hollow tunnel is not positioned at the centre of an exterior surface of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, in particular a top (superior) or bottom (inferior) surface of the implantas it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.

[0081] A discrete hollow tunnel(s) may be independently positioned at any angle extending into the porous osteoconductive scaffold. A discrete hollow tunnel(s) may independently extend into the porous osteoconductive scaffold in any direction. A discrete hollow tunnel(s) may extend in the same or a different direction as the other hollow tunnel of the implant. Each discrete hollow tunnel may extend in the same or different direction. A discrete hollow tunnel(s) may have any orientation with respect to the exterior surface of the implant on which it has an opening(s). A discrete hollow tunnel(s) may have any angle independently selected from 10 to 170° with respect to the exterior surface of the implant on which it has an opening(s), preferably from 25 to 155°. This is preferably the initial angle of the discrete hollow tunnel(s) as it extends away from the exterior surface. The angle may be determined visually, or by micro-CT imaging, as described herein.

[0082] A discrete hollow tunnel(s) may be independently selected to be straight, substantially straight, or curved. By ‘straight’ is meant the discrete hollow tunnel extends in one direction only without a curve or bend. By ‘substantially straight’ is meant that the discrete hollow tunnel extends in one direction but may deviate therefrom by an angle of 12° or less, such as 5° or less, for some or all of its length, such as by an angle of from 0° to 12°, or from 0° to 5°, for some or all of its length. By ‘curved’ is meant that the discrete hollow tunnel extends in one direction but deviates therefrom by an angle of from 11 to 35°, or 13 to 35°, such as 15 to 30°, for some or all of its length. Preferably, one discrete hollow tunnel, such as two or more, or three or more, or four or more discrete hollow tunnels, more preferably each discrete hollow tunnel, is independently selected to be straight or substantially straight. This may be determined visually, or by micro-CT imaging, as described herein.

[0083] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may comprise any suitable number of discrete hollow tunnels. As described herein, this not only depends on the overall dimensions and shapeof the implant, but on the specific patient need and orthopaedic application. Preferably, the implant according to the first or second aspect of the present invention comprises two or more discrete hollow tunnels, preferably three or more discrete hollow tunnels, such as four or more discrete hollow tunnels. Each of the discrete hollow tunnels may be the same or different as outlined herein. The properties of each discrete hollow tunnel may be independently selected as defined herein.

[0084] The discrete hollow tunnels, in total, may have a volume of 40% or less of the volume of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. Preferably, 35% or less, such as 30% or less, or 25% or less, such as 20% or less, or 15% or less, and more preferably 10% or less. The discrete hollow tunnels, in total, may have a volume of from 1% to 40% of the volume of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. Preferably, the discrete hollow tunnels, in total, may have a volume of from 1% to 35% of the volume of the 3D-printed orthopaedic implant, such as from 1% to 30%, or from 1% to 25%, such as from 1 % to 20%, or from 1 % to 15%, and more preferably from 1 % to 10%. The volume may be measured visually or by micro-CT imaging, as defined herein. The volume of the discrete hollow tunnels refers to the volume of the empty space (‘negative’ space) formed by at least one discrete hollow tunnel within the implant, when not filled with a solid osteoinductive filament.

[0085] It will be appreciated that if a central graft chamber is present, the total volume of the discrete hollow tunnels is preferably reduced such that the combined volume of the discrete hollow tunnels and the central graft chamber is 60% or less of the volume of the implant, such as 55% or less, or 50% or less. For example, the combined volume of the discrete hollow tunnels and the central graft chamber is from 35% to 60% of the volume of the implant, such as from 35% to 55%, preferably from 40% to 50% of the volume of the implant.

[0086] Each discrete hollow tunnel has a volume of 7% or less of the volume of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, such as 5% or less of the volume of the implant. Preferably, onediscrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, independently has a volume of 7% or less, such as 5% or less, of the volume of the implant. A discrete hollow tunnel, such as two or more, or three or more, or four or more, more preferably each discrete hollow tunnel, may independently have a volume of 1 % or more of the volume of the 3D-printed orthopaedic implant (as described herein). Each discrete hollow tunnel may independently have a volume of from 1 % to 7%, such as 1 % to 5% of the volume of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. Preferably, one discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, independently has a volume of from 1 % to 7%, or from 1 % to 5%, of the volume of the implant. The volume of each hollow tunnel may be independently selected from the values defined herein. Each discrete hollow tunnel may have the same or a different volume. Preferably one discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has the same volume. The volume may be measured visually or by micro-CT imaging, as defined herein.

[0087] A discrete hollow tunnel(s) may have any suitable width. As described herein, this not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application. The width of a discrete hollow tunnel(s) is the distance from side to side of the tunnel as it extends into the implant. It is a continuous dimension. Where the cross-section or cross-sectional shape of the tunnel is a circle or substantially circular, the width refers to the diameter of the tunnel. Preferably, the discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has a width independently selected to be 5 mm or less, or 4 mm or less, such as 3 mm or less, or 2 mm or less, and more preferably 1.5 mm or less. Preferably, one discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has a width independently selected to be 0.15 mm or more, preferably 0.3 mm or more, and more preferably 0.5 mm or more. The discretehollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, may have a width independently selected to be from 0.15 to 5 mm, or from 0.15 to 4 mm, such as from 0.3 to 3 mm, or from 0.5 to 2 mm, and more preferably from 0.8 to 1.5 mm. Preferably, the at least one discrete hollow tunnel has a width of from 0.5 mm to 2 mm, more preferably from 0.8 mm to 1.5 mm. The width of each hollow tunnel is independently selected from the values defined herein. The width of each discrete hollow tunnel may be the same or different. Preferably, one discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has the same width. The width of the at least one discrete hollow tunnel may be measured visually, e.g. using a measuring instrument such as a ruler or tape, or by micro-CT imaging, as described herein.

[0088] A discrete hollow tunnel(s) may have any suitable length. The length of a discrete hollow tunnel(s) is the distance from end (opening) to end (opening or blind-end) of the tunnel in its longest dimension. It is a continuous dimension. If a discrete hollow tunnel has any bend or curve, the length of the discrete hollow tunnel is the distance from end to end following the curve or bend as it extends into the porous osteoconductive scaffold. As described herein, this not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application. Preferably, the discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has a length independently selected to be at least 1 mm, such as at least 4 mm, more preferably at least 8 mm, or at least 10 mm. The discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, may have a length independently selected to be from 1 to 70 mm, such as from 4 to 70 mm, more preferably from 8 to 70 mm, or from 10 to 70 mm. Each discrete hollow tunnel has a length of at least three times its width. Preferably, one discrete hollow tunnel, such as two or more discrete hollow tunnels, three or more, or four or more, more preferably each discrete hollow tunnel, has a length of at least four times its width, preferably at least five times its width, such as at least six times its width.The length of each hollow tunnel is independently selected from the values defined herein. The length of each discrete hollow tunnel may be the same or different. The length of the at least one discrete hollow tunnel may be measured visually, e.g. using a measuring instrument such as a ruler or tape, or by micro-CT imaging, as described herein.

[0089] A discrete hollow tunnel(s) may independently be selected to be a blind-end tunnel or extend completely through the implant according to the first or second aspect of the present invention. By the term ‘blind-end’ as used herein refers to a discrete hollow tunnel that extends into, but does not extend completely through the implant. Such a discrete hollow tunnel will only have one opening of an exterior surface of the implant. For blind-end discrete hollow tunnels, the tunnel preferably extends at least 1 / 3 of the distance required for the discrete hollow tunnel to extend completely through the implant (the distance measured in the direction in which the tunnel extends), preferably over , such as % or more, and more preferably stops just short of extending completely though the implant. Preferably, one discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, is a blind-end tunnel.

[0090] A discrete hollow tunnel(s) may have any suitable cross-section. By this is meant that a discrete hollow tunnel(s) may have any suitable cross-sectional shape. The cross-sectional shape may be, for example, square, elliptical, oval, circular, rectangular, or substantially circular. Where the cross-section or cross-sectional shape of a discrete hollow tunnel is a circle or substantially circular, the width refers to the diameter of the discrete hollow tunnel. Preferably, the cross-section or cross-sectional shape of a discrete hollow tunnel(s) is elliptical, oval, circular or substantially circular, such as circular or substantially circular. By ‘substantially circular’ is meant a cross-section of the discrete hollow tunnel that a skilled person would consider as being circular. The shape is principally a circle, but may deviate slightly therefrom caused by the 3D-printing process (the manufacture technique), and / or by the porous nature of the porous osteoconductive scaffold through whichit extends. This may be determined visually, or by micro-CT imaging as described herein.

[0091] The cross-section or cross-section shape of a hollow tunnel(s) is independently selected as defined herein. The cross-section or cross-sectional shape of each discrete hollow tunnel may be the same or different. Preferably, a discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has a circular, or substantially circular cross-section. Preferably, a discrete hollow tunnel, such as two or more discrete hollow tunnels, or three or more, or four or more, more preferably each discrete hollow tunnel, has the same cross-section or cross-sectional shape.

[0092] The porous osteoconductive scaffold and when present, the non-porous solid portion, may be formed from the same or different materials. Preferably, the porous osteoconductive scaffold and when present, the non-porous solid portion, are formed from the same material. Formation from the same material is advantageous as it streamlines production and reduces costs.

[0093] When present, the non-porous solid portion of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may be formed from a non-resorbable material. When present, the non-porous solid portion of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may be formed from a non-resorbable material selected from: non-resorbable metals or alloys thereof, or combinations thereof; and non-resorbable polymers or combinations thereof; or combinations thereof. Suitable non-resorbable metals include titanium, aluminium, vanadium, niobium, cobalt, chromium, stainless steel, and tantalum. Examples include CP-Ti, grades 1 to 4, or alloys thereof. Examples of suitable metal alloys include titanium alloys such as titanium-aluminium-vanadium and titanium-aluminium-niobium alloys, for example, Ti-6AI-4V, and Ti-6AI-7Nb. Suitable non-resorbable polymers include polyether ether ketone (PEEK) or polyether ketone ketone (PEKK). Preferably, the non-porous solid portion is formed from a non-resorbable material selected from: titanium or an alloy thereof, and polyether ether ketone, or a combination thereof.The porous osteoconductive scaffold of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may be formed from a material selected from: non-resorbable metals or alloys thereof, or combinations thereof; and non-resorbable polymers or combinations thereof; resorbable polymers, or combinations thereof; and resorbable metals or combinations thereof; or combinations thereof. By ‘resorbable’ as used herein is meant that the material is capable of being broken down and reabsorbed in the body. Suitable non-resorbable metals include titanium, aluminium, vanadium, niobium, cobalt, chromium, stainless steel, and tantalum. Examples include CP-Ti, grades 1 to 4, or alloys thereof. Examples of suitable metal alloys include titanium alloys such as titanium-aluminium-vanadium and titanium-aluminium-niobium alloys, for example, Ti-6AI-4V, and Ti-6AI-7Nb. Suitable non-resorbable polymers include polyether ether ketone (PEEK) or polyether ketone ketone (PEKK). Suitable resorbable metals include magnesium alloys. Suitable resorbable polymers include polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and polylactic-co-glycolic acid (PLGA), or combinations thereof. Preferably, the porous osteoconductive scaffold is formed from a material selected from: non-resorbable metals or alloys thereof, or combinations thereof; and non-resorbable polymers or combinations thereof; or combinations thereof. Preferably, the porous osteoconductive scaffold is formed from a material selected from: titanium or an alloy thereof, and polyether ether ketone, or a combination thereof.

[0094] If the porous osteoconductive scaffold of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is formed from a material selected from: a resorbable metal and / or resorbable polymer, then the non-porous solid portion, when present, is preferably formed of a material selected a non-resorbable metal or alloy thereof and / or non-resorbable polymer. The resorbable metal, resorbable polymer, metal or alloy, and non-resorbable polymer are as described above for the non-porous support portion and porous osteoconductive scaffold.When present, the non-porous support portion of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention may be formed from a non-resorbable material as defined herein, and the porous osteoconductive scaffold may be formed of a resorbable material as defined herein.

[0095] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, may be fabricated for any orthopaedic application including, but not limited to, foot and ankle implants, craniomaxillofacial, dental, long bone implants, extremity implants, bone implants for bone fusion and / or formation, spinal implants for spinal fusion, and joint implants. Suitable designs for 3D-printed orthopaedic implants for different applications in the body are known in the art.

[0096] Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is fabricated for bone implants for bone fusion and / or formation, such as for spinal implant and / or fusion procedure or craniofacial work relating to the jaw and / or associated dental work. Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is fabricated for bone fusion procedures, such as spinal fusion procedures.

[0097] In particular, the 3D-printed implant according to the first or second aspect of the present invention is preferably fabricated for spinal implants and / or spinal fusion procedures. With respect to implants for spines, intervertebral (interbody), intervertebral (intrabody), and vertebral implants may be fabricated. Interbody devices that sit between vertebra in the spine for spinal fusion procedures.

[0098] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention may therefore be a bone implant and / or bone tissue scaffold, preferably a spinal implant such as a spinal fusion implant, and more preferably a spinal interbody fusion implant. Spinal fusion involves inserting the implant between vertebrae, in place of the normal intervertebral disc.Spinal interbody fusion implants include TLIF (transforaminal lumbar interbody fusion) implants, XLIF (extreme lateral interbody fusion) implants, PLIF (posterior lumbar interbody fusion) implants, lateral implants, OLID (oblique lateral interbody fusion) implants, ACDF (anterior cervical discectomy and fusion) implants, OCF (occipitocervical fusion) implants, PCF (posterior cervical fusion) implants, and ALIF (anterior lumbar interbody fusion) implants.

[0099] The 3D-printed orthopaedic implant according to the first, second, sixth or seventh aspect of the present invention is suitable for placing in space between two bones or areas of bone to replace missing bone. The purpose of the implants of the present invention is to fill the space and facilitate bone growth therethrough so as to join and fuse areas of bone or two bones or pieces of bones together. Preferably, the 3D-printed orthopaedic implant is positioned in intervertebral space.

[0100] The 3D-printed orthopaedic implant of the first, second, sixth or seventh aspect of the present invention may be used in a lateral insertion procedure, an anterior insertion procedure, or a posterior insertion procedure.

[0101] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention is formed by 3D-printing or other additive manufacturing techniques, as known in the art. For example, the implant may be manufactured using Powder Bed Fusion (PBF) technology, either by Selective Laser Melting (SLM) or Electron Beam Melting (EBM). SLM uses a high-power laser to selectively melt titanium powder layer by layer. In an exemplified process, a recoater blade or roller spreads a thin layer (typically 30-50 pm) of titanium powder over the build platform. A high-power laser selectively melts the powder in the pre-defined computer aided design model pattern. Melting occurs under an inert gas environment (argon or nitrogen) to prevent oxidation. The laser fully fuses the powder particles, ensuring high mechanical strength. The build platform lowers by one layer thickness (for example, around 30-50 pm), and a new powder layer is spread. This process repeats until the entire implant is formed. Electron Beam Melting (EBM) is an alternative Powder Bed Fusion (PBF) process that uses an electron beam instead of a laser. Similar to SLM, in an exemplified process, athin layer (for example, 50-100 pm) of titanium powder is spread. A high-energy electron beam scans the powder bed, fully melting the powder. The process occurs in a high-vacuum environment, preventing oxidation. The platform lowers, and a new powder layer is spread, repeating until completion of the implant. These example processes allow for the creation of osteoconductive scaffolds which resemble the structure of mature woven bone, whilst allowing the inclusion of discrete hollow tunnels.

[0102] For example, the SLM process may be conducted under the following parameters:

[0103] • Material: Ti-6AI-4V (ASTM F136, medical-grade);

[0104] • Layer Thickness: 20-50 pm;

[0105] • Laser Power: 200-400 W;

[0106] • Scan Speed: 800-1500 mm / s;

[0107] • Hatch Spacing: 50-120 pm;

[0108] • Build Atmosphere: Inert gas (argon or nitrogen) to prevent oxidation;

[0109] • Preheat Temperature: 100-200°C to reduce residual stress; and

[0110] • Lattice Porosity: 50-80% with strut thickness of 100-500 pm.

[0111] After printing, the as-built implant may undergo post-processing steps to enhance its mechanical and biological properties, such as: (1) Stress Relief Annealing at 800-950°C in a vacuum or argon atmosphere to reduce internal stresses. (2) Hot Isostatic Pressing (HIP) at 900-1000°C under 100-150 MPa to improve density and mechanical integrity. (3) Surface Modification, including acid etching, grit blasting, or anodization, to enhance osteointegration and biocompatibility.

[0112] These manufacturing parameters may be adjusted based on implant design specifications, mechanical performance requirements, and regulatory standards applicable to the implant.

[0113] Each discrete hollow tunnel of the 3D-printed orthopaedic implant according to the first or second aspect of the present invention is configured to allow insertion of a solid osteoinductive filament therein. As described herein, such solid dosages of osteoinductive material have not been utilised in implants before. The lack of suchhas prevented, before now, the production of 3D-printed implants operable to achieve more uniform distribution of osteoinductive material throughout an osteoconductive implant structure, with the use of the novel discrete hollow tunnels.

[0114] The solid osteoinductive filament(s) of the present invention comprises an osteoinductive agent.

[0115] The term ‘osteoinductive’ and like terms used herein has the same meaning as known in the art and refers to the stimulation of progenitor cells to differentiate into osteoblasts, the cells responsible for new bone formation. This process is mediated by an osteoinductive agent. Osteoinductive materials actively recruit and promote the differentiation of mesenchymal stem cells (MSCs), making them important for bone healing in sites with limited cellular activity.

[0116] Any suitable osteoinductive agent may be utilised. The osteoinductive agent may be selected from any bone morphogenic protein (BMP), or combination thereof. The osteoinductive agent may be a chimeric or engineered version of BMP. The osteoinductive agent may also be indirectly osteoinductive, or pro-osteoinductive, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), sclerostin-binding molecules, and bisphosphonates, or combinations thereof. Suitable bone morphogenic proteins include recombinant human bone morphogenic proteins (rhBMP), such as rhBMP-2 or rhBMP-7.

[0117] Preferably, the osteoinductive agent is a bone morphogenic protein, or combination thereof. For example, a bone morphogenic protein selected from BMP-2, BMP-9, BMP-6, BMP-4 and BMP-7, or combinations thereof. More preferably, the osteoinductive agent is a bone morphogenic protein selected from BMP-2, BMP-9, BMP-6, BMP-4, and BMP-7, such as BMP-2, BMP-9, and BMP-6. More preferably, the osteoinductive agent is a recombinant human form of bone morphogenic protein. More preferably, the osteoinductive agent is rhBMP-2.

[0118] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printedorthopaedic implant according to the sixth or seventh aspect of the present invention, the osteoinductive agent of each filament is independently selected from those defined herein. Each filament may be the same or different. Each filament may comprise a different or the same osteoinductive agent. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, comprises the same osteoinductive agent. Preferably, for a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, the osteoinductive agent is a bone morphogenic protein, such as a recombinant human bone morphogenic protein, preferably, the osteoinductive agent is rhBMP-2.

[0119] When the osteoinductive agent is a bone morphogenic protein, such as a recombinant human bone morphogenic protein, preferably BMP-2 or rhBMP-2, the solid osteoinductive filament may comprise 0.1 to 50 pg of osteoinductive agent per milligram of the solid osteoinductive filament. Preferably, 0.5 to 30 pg, such as 1 to 20 pg, or 1.5 to 10 pg, or 2 to 5 pg of osteoinductive agent per milligram of the solid osteoinductive filament.

[0120] The osteoinductive agent may be present in the solid osteoinductive filament according to the third aspect of the present invention in an amount of 0.05 to 2 wt%. Preferably, the osteoinductive agent is present in the solid osteoinductive filament in an amount of 0.1 to 1 wt% of the solid osteoinductive filament, and more preferably 0.15 to 0.5 wt%.

[0121] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may comprise an amount (pg dose or wt%) of osteoinductive agent independently selected from the values defined herein. Each filament may have the same or different amounts (pg dose or wt%) of osteoinductive agent. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has the same amount (pg dose or wt%) of osteoinductive agent. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably eachfilament, comprises 0.1 to 50 pg of osteoinductive agent per milligram of the solid osteoinductive filament, such as 0.5 to 30 pg, or 1 to 20 pg, or 1.5 to 10 pg, or 2 to 5 pg of osteoinductive agent per milligram of the solid osteoinductive filament.

[0122] It will be appreciated that, in use, the solid osteoconductive filament will facilitate delivery of the osteoinductive agent to the localised treatment site. Preferably, the solid osteoinductive filament will degrade to facilitate release and delivery of the osteoinductive agent. The release profile of the osteoinductive agent may be modified by modifying the properties of the filament defined herein, and tailored to a particular application, as required.

[0123] By the term ‘solid’ as used herein in the context of the osteoinductive filament(s) is meant dry and non-liquid, and preferably non-porous.

[0124] The solid osteoinductive filament(s) according to the third aspect of the present invention is preferably not a putty or a paste. The solid osteoinductive filament(s), as described herein, has a continuous structure that is preferably uniform. The solid osteoinductive filament(s) has a structure that is preferably characterised by consistent material properties throughout its length. The solid osteoinductive filament(s) is not composed of discrete particles, loosely held together, but preferably a homogenous, semi-malleable material that maintains its structural integrity without the ability to be separated and reconstituted. Unlike a putty or injectable bone graft material, which consists of a collection of discrete particles held together by a binder or cohesive forces to allow for moulding and adaptation to irregular geometries, the solid osteoinductive filament(s) is preferably inherently uniform in shape and preferably cannot be manipulated to conform to wide variety of shapes as a putty or fluid can. The filament is preferably not injectable as a liquid, nor does it preferably exhibit fluid-like behaviour; instead, it preferably retains its defined form without external support. The solid osteoinductive filament(s) is preferably non-flowable. The solid osteoinductive filament(s) is preferably non-spreadable. When held at one end (less than 10% of the length), without support across the remaining length of the filament, preferably, the degree of sag or deformation of the filament across its length is less than 70° after at least15 minutes of gravitational strain, such as less than 60 , or less than 50 , more preferably less than 35°.

[0125] The term ‘filament’ as used herein has the same meaning as known in the art, and refers to a slender elongated thread-like object. A particle or pellet is preferably not encompassed by this term. The solid osteoinductive filament has a continuous structure.

[0126] The solid osteoinductive filament may have any suitable width. The width of the solid osteoinductive filament is the distance from side to side of the filament. It is a continuous dimension. Where the cross-section or cross-sectional shape of a filament is a circle or substantially circular, the width refers to the diameter of the filament. As described herein, this not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application. The solid osteoinductive filament may have a width of 5 mm or less, or 4 mm or less, such as 3 mm or less, or 2 mm or less, and more preferably 1.5 mm or less, or 1.2 mm or less. The solid osteoinductive filament may have has a width of 0.15 mm or more, preferably 0.3 mm or more, and more preferably 0.5 mm or more. The solid osteoinductive filament may have a width of from 0.15 mm to 5 mm, or 0.15 mm to 4 mm, such as from 0.3 mm to 3 mm, or from 0.3 mm to 2 mm, or from 0.5 mm to 1.5 mm, more preferably, the solid osteoinductive filament has a width of from 0.8 mm to 1.2 mm. The width of the solid osteoinductive filament(s) may be measured visually, e.g. using a measuring instrument such as a ruler or tape, or by micro-CT imaging, as described herein.

[0127] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may have a width independently selected from the values defined herein. Each filament may have the same or a different width. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has the same width. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has a width of 5 mm or less, or 4 mm or less, such as 3 mm or less, or 2 mm orless, and more preferably 1.5 mm or less. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has a width of 0.15 mm or more, preferably 0.3 mm or more, and more preferably 0.5 mm or more. A filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, may have a width of from 0.15 mm to 5 mm, such as from 0.15 mm to 4 mm, or from 0.3 mm to 3 mm, such as from 0.3 mm to 2 mm, or from 0.5 mm to 1.5 mm.

[0128] The solid osteoinductive filament may have any suitable length. The length of the solid osteoinductive filament is the distance from end to end of the filament in its longest dimension. It is a continuous dimension. If the filament has a bend or curve, the length is the distance along the full length of the filament following the bend or curve. If the filament has a bend or curve, the length is that of the filament if it was straightened. As described herein, this not only depends on the overall dimensions and shape of the implant, but on the specific patient need and orthopaedic application. The solid osteoinductive filament may have a length of at least 1 mm, such as at least 4 mm, more preferably at least 8 mm, or at least 10 mm. The solid osteoinductive filament may have a length of from 1 mm to 70 mm, such as from 4 mm to 70 mm , more preferably from 8 mm to 70 mm , or from 10 mm to 70 mm. The solid osteoinductive filament has a length of at least three times its width. Preferably, the solid osteoinductive filament has a length of at least four times its width, preferably at least five times its width. The length of the solid osteoinductive filament(s) may be measured visually using a measuring instrument such as a ruler or tape, or by micro-CT imaging, as described herein.

[0129] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may have a length independently selected from the values defined herein. Each filament may have the same or a different length. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has a length of at least 1 mm, such as at least 4 mm, more preferably at least 8 mm, or at least 10 mm. A filament, such astwo or more filaments, or three or more, or four or more, more preferably each filament, may have a length of 1 mm to 70 mm, such as from 4 mm to 70 mm, more preferably from 8 mm to 70 mm or from 10 mm to 70 mm. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has a length of at least four times its width, preferably at least five times its width.

[0130] The solid osteoinductive filament may be straight, substantially straight, or curved. By ‘straight’ is meant the filament extends in one direction only without a curve or bend. By ‘substantially straight’ is meant that the filament extends in one direction but may deviates therefrom by an angle of 12° or less, such as 5° or less, for some or all of its length or may deviate therefrom by an angle of 0° to 12°, such as 0° to 5°, for some or all of its length. By ‘curved’ is meant that the filament extends in one direction but deviates therefrom by an angle of from 11 to 35°, or from 13 to 35°, such as 15 to 30°, for some or all of its length.

[0131] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the six or seventh aspect of the present invention, each filament may be independently selected to be straight, substantially straight or curved. Each filament may be the same or a different. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, is straight or substantially straight.

[0132] The solid osteoinductive filament may have any suitable cross-section. Preferably, the solid osteoinductive filament has a uniform cross-section. By this is meant that the cross-section is continuous (the same) throughout the length of filament. It is uniform in shape and size throughout the length of the filament. The filament may have any suitable cross-sectional shape. The cross-sectional shape may be, for example, square, elliptical, oval, circular, rectangular, or substantially circular. Where the cross-section or cross-sectional shape of a filament is a circle or substantially circular, the width refers to the diameter of the filament. Preferably, the filament has a elliptical, oval, circular, or substantially circular cross-section, such as a circular or substantially circular cross-section. By ‘substantially circular’is meant a cross-section of the filament that a skilled person would consider as being circular. The shape is principally a circle, but may deviate slightly therefrom caused by the manufacture technique, and / or by the nature of material from which the filament is formed. This may be determined visually, or using micro-CT imaging, as defined herein.

[0133] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the six or seventh aspect of the present invention, each filament may have a cross-section or cross-sectional shape independently selected as defined herein. Each filament may have the same or a different cross-section or cross-sectional shape. Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, has the same cross-section or cross-sectional shape.

[0134] The discrete solid osteoinductive filament may be formed of a material comprising a polymer or a ceramic, or combination thereof, the material having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein.

[0135] By the term ‘incorporated’ or like terms used herein in reference to the osteoinductive agent in the filament is meant the presence of the agent within and distributed throughout the material forming the filament, such as the polymer as described herein. A composite material comprising osteoinductive agent is preferably formed. Incorporation does not describe an agent that have been attached or tethered to the surface of a filament, or surface loaded, or loaded into pores.

[0136] By the term ‘attached thereto’ or like terms used herein in reference to the osteoinductive agent is meant to include (i) adsorption (passive binding) of the agent using electrostatic and van der Waals interactions, (ii) ionic binding in which positively or negatively charge regions of the agent are attracted to the opposite charge on the surface of the delivery material (e.g. hydroxyapatite) or (iii) covalentbonding such as crosslinking via functional groups such as COOH, and -NH2. The osteoinductive agent is attached to the exterior of the filament.

[0137] By the term ‘tethered thereto’ or like terms used herein in reference to the osteoinductive agent is meant the addition of amino acid sequences or peptides to the osteoinductive agent to form a chimeric version, where the amino acid sequence or peptide have increased propensity for binding onto (tethering to) the filament. Examples of amino acids with known strong binding residues to calcium phosphates include: Aspartic Acid (D), Glutamic Acid (E), Serine (S), Threonine (T), and Histidine (H). Examples of amino acids with weak binding residues include: Leucine (L), Valine (V), Isoleucine (I), Proline (P), Glycine (G), Alanine (A), Phenylalanine (F), Tyrosine (Y). Examples of mixed binding residues include, but are not limited to: Arginine (R), Lysine (K), Asparagine (N), Glutamine (Q). Those skilled in the art will understand that any sequence of amino acids which include a number of high binding residues may be selected. For example, the identification of calcium phosphate-binding peptides may use a Phage Display and / or Computational Modelling. To identify peptides with a high affinity for calcium phosphate (CaP) surfaces, a phage display technique may be used. Commercial M13 phage library displaying randomized 12-amino acid sequences may be incubated with hydroxyapatite (Cai0(PO4)6(OH)2)-coated surfaces. Phages that bound strongly are able to be isolated, amplified, and subjected to additional selection rounds to enrich for high-affinity peptide sequences. Several rounds of selection may allow for the sequencing of the strongest binding phage clones identified a consensus peptide sequence, such as Asp-Glu-Glu-Asp-Ser-Thr-Gly-Ser-Gly-Ser-Asp-Glu (DEEESTGSGSDE). To further evaluate and optimize this peptide, computational modelling may be performed: For example: Molecular Docking (AutoDock Vina) may be used to predict the binding interactions between the peptide and a hydroxyapatite crystal structure to confirm the peptide exhibits strong electrostatic interactions with calcium ions. Molecular Dynamics Simulations (GROMACS) may be conducted to assess the stability of the peptide-CaP complex over time. Evaluation of the peptide binding to the surface may be done under simulated physiological conditions. Further sequence optimization may be performed using machine learning-based prediction models,leading to a refined sequence with enhanced CaP-binding properties. Thus, phage display and computational modelling may be used together to identify and refine peptides with strong affinity for calcium phosphate surfaces, and utilised to tether osteoinductive agents to the surface of the filaments.

[0138] The osteoinductive agent may be attached or tethered to the exterior of the filament, or incorporated within. The osteoinductive agent may be attached or tethered to the exterior of the material forming the filament, or incorporated within the material forming the filament.

[0139] The discrete solid osteoinductive filament may be formed of:

[0140] (a) a material comprising a ceramic, and having the osteoinductive agent attached and / or tethered thereto;

[0141] (b) a material comprising a polymer, and having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein, preferably incorporated therein; and

[0142] (c) a material comprising a polymer and ceramic, for example a composite material of polymer and ceramic, and having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein.

[0143] For (a) and (c), the ceramic may be selected from calcium sulphate, calcium carbonate, calcium phosphate, a-tricalcium phosphate, p-tricalcium phosphate, and hydroxyapatite, or combinations thereof.

[0144] For (a), the material may consist of ceramic having the osteoinductive agent attached thereto and / or tethered thereto.

[0145] For (b), preferably the material does not further comprise ceramic.

[0146] For (c), the material, and thus the filament, may comprise from 1 to 99 wt% ceramic, such as 30 to 85 wt%, preferably 40 to 80% wt%, or most preferably 65 to 73 wt%.For (b) and (c), the polymer may be a biodegradable polymer. The polymer may be selected from the group comprising poly (lactide-co-glycolide) (PLGA), poly lactic acid (PLA), polyethyleneimine (PEI), polylactic or polyglycolic acids, polylactide poly-glycolide copolymers, and poly-lactide, poly-glycolide, polyethylene glycol copolymers, polyethylene glycol (PEG), polyesters, poly (s-caprolactone), poly (3-hydroxy-butyrate), poly (s-caproic acid), poly (p-dioxanone), poly (propylene fumarate), poly (ortho esters), polyol / diketene acetals addition polymers, polyanhydrides, poly (sebacic anhydride) (PSA), poly (carboxybiscarboxyphenoxyphosphazene) (PCPP), poly [bis (p-carboxyphenoxy) methane] (PCPM), copolymers of SA, CPP and CPM, poly (amino acids), poly (pseudo amino acids), polyphosphazenes, derivatives of poly [(dichloro) phosphazene], poly [(organo) phosphazenes], polyphosphates, polyethylene glycol polypropylene block co-polymers, natural or synthetic polymers, silk, elastin, chitin, chitosan, fibrin, fibrinogen, polysaccharides, peptides, polypeptides±proteins, copolymers prepared from the monomers of any of these polymers, or blends, mixtures or combinations thereof.

[0147] Two enantiomeric isomers of lactide exist (D-lactide and L-lactide). Poly (lactide-co-glycolide) (PLGA) as described herein includes the L-form (poly (L-lactide-co-glycolide), D-form (poly (D-lactide-co-glycolide), and D, L-form (poly (D,L-lactide-co-glycolide). Preferably, the D,L- form is used. The PLGA may be acid-terminated. Poly (lactic acid) (PLLA) as described herein includes the L- form (poly(L-lactic acid), the D- form (poly(D-lactic acid), and the D, L- form (poly(D,L-lactic acid). Preferably, the D,L- form is used.

[0148] Preferably, the polymer is selected from poly (lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), chitosan, or blends, mixtures or combinations thereof. More preferably a combination of poly (lactide-co-glycolide) and chitosan, or poly (lactide-co-glycolide) and polyethylene glycol. Preferably, the poly (lactide-co-glycolide) (PLGA) used is poly (D,L-lactide-co-glycolide). poly (D,L-lactide-co-glycolide) is amorphous and advantageously degrades quickly and more uniformly.When the polymer is selected to be, or include, PLGA, the PLGA may comprise different lactide to glycolide ratios, such as from 10:90 to 90:10, or from 15:85 to 85:15, or from 25:75 to 75:25, preferably 45:40 to 55:45, and more preferably 50:50. The ratio may be adjusted and / or optimised for degradation of the polymer to provide an appropriate osteoinductive agent release profile depending upon the orthopaedic application required.

[0149] The polymer may have a weight-average molecular weight (Mw) of from 40kDa to 80 kDa, such as from 60kDa and 70 KDa. This can be measured using a technique such as Size Exclusion Chromatography (SEC).

[0150] For (b) and (c), the material, and thus the filament, may comprise from 10 to 90 wt% polymer, such as from, such as from 20 to 85 wt% polymer, preferably 60 to 80 wt% polymer. Such amounts are optimal for the processing of the polymer in formation of the filaments as discussed below, in particular in the presence of other components, such as cyclodextrin.

[0151] For (b) and (c), the material, and thus the filament, may further comprise one or more additional component selected from: cyclodextrin, arginine or a salt thereof, trehalose, sucrose, dextran, polyethylene glycol (PEG), or combinations thereof. Suitable cyclodextrins include 2-hydroxypropyl-p-cyclodextrin.

[0152] Preferably, for (b) and (c), the material, and thus the filament, comprises one or more additional component. Preferably, for (b) and (c), the material, and thus the filament, further comprises a cyclodextrin, such as 2-hydroxypropyl-p-cyclodextrin. Advantageously, a cyclodextrin provides protection to the osteoinductive agent, such as BMPs, during formation of the filaments, such as during a hot melt extrusion process. A cyclodextrin such as 2-hydroxypropyl-p-cyclodextrin may advantageously protect the activity of the osteoinductive agent, e.g. BMPs from the filament, during manufacture.

[0153] Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by a-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. Typical cyclodextrins areconstituted by 6-8 glucopyranoside units. These subunits are linked by 1,4 glycosidic bonds. The cyclodextrins have toroidal shapes, with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively, p (beta)-cyclodextrin has 7 glucose subunits.

[0154] For (b) and (c), the material, and thus the filament, may comprise from 5 to 50 wt% of the additional component, such as from 7 to 30 wt%, or from 10 to 20 wt%, or from 12 to 15 wt%.

[0155] For (b) and (c), the material, and thus the filament, may further comprise a surfactant. The surfactant may be selected from a poloxamers, polysorbate, or combinations thereof. Suitable poloxamers include poloxamer 407.

[0156] Preferably, the material, and thus the filament, further comprises a surfactant. Preferably, the material, and thus the filament, further comprises poloxamer 407. Advantageously, a poloxamer aids in protecting the osteoinductive agent from shear stress during manufacture. Advantageously, a poloxamer aids the controlled release of the osteoinductive agent from the filament. Additionally, it advantageously does not significantly affect pH levels. The level of poloxamer may be modified to alter and / or optimise the release rate of the osteoinductive agent for different orthopaedic applications

[0157] Poloxamer 407 is a hydrophilic non-ionic surfactant of the more general class of copolymers known as poloxamers. Poloxamer 407 is a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol (PEG).

[0158] For (b) and (c), the material, and thus the filament, may comprise from 5 to 35 wt%, such as from 10 to 30 wt%, of the surfactant.

[0159] Preferably, the solid osteoinductive filament is formed of:

[0160] (b) a material comprising a polymer, and having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein.More preferably, the solid osteoinductive filament is formed of:

[0161] (b) a material comprising a polymer, and having the osteoinductive agent incorporated therein.

[0162] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may be formed of the same or different material. Each filament may be formed from a material independently selected from those defined herein, e.g. from (a), (b) and (c). Preferably, a filament, such as two or more filaments, or three or more, or four or more filaments, is formed from the same material. Preferably each filament is formed from the same material, e.g. material (a), (b) or (c), preferably (b). Preferably, a filament, such as two or more filaments, or three or more, or four or more, more preferably each filament, is formed from material (b).

[0163] The solid osteoinductive filament may have a hollow (e.g. a lumen) extending completely through the filament along its length. Preferably, the hollow extends through the centre of the filament. Preferably, the hollow has the same cross section or cross-sectional shape as the filament. When the solid osteoinductive filament comprises a hollow (e.g. a lumen), it may be considered to be a tube, or tubular in shape. When the solid osteoinductive filament comprises a hollow, the widths described above for the filament refer to the largest width of the filament, not of the hollow. Preferably, the solid osteoinductive filament does not have a hollow extending completely through the filament along its length.

[0164] When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may be independently selected to comprise a hollow or not. Each filament may be the same or different.The solid osteoinductive filament of the present invention may be formed by any suitable method. When more than one solid osteoinductive filament is used, for example, in the kit according to the fourth or fifth aspect of the present invention or the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, each filament may be formed by the same or different methods, as described herein. Preferably, a filament, such as two or more filaments, or three or more, or four or more filaments, more preferably each filament, is formed by the same method.

[0165] Preferably, the method for forming the solid osteoinductive filament does not utilise a plasticising fluid. Preferably, the method for forming the solid osteoinductive filament does not comprise contacting a polymer and osteoinductive agent with a supercritical fluid under supercritical conditions of elevated temperature and / or pressure. A ‘supercritical fluid’ is a substance at a temperature and pressure above its critical point, where distinct liquid and gas phases do not exist, but below the pressure required to compress it into a solid. Preferably, the method for forming the solid osteoinductive filament does not comprise extrusion under supercritical conditions. ‘Supercritical conditions’ refer to a state where a substance, such as water, is above its critical temperature and pressure, leading to unique properties like a single homogenous fluid phase with characteristics between a gas and a liquid.

[0166] The solid osteoinductive filament may be formed by combining polymer and optionally ceramic (for a polymer and ceramic composite), with the osteoinductive agent to form a mixture. The mixture may be melted and extruded to form the filament, preferably by hot melt extrusion. Alternatively, the mixture may be dissolved in an organic solvent and ejected through an electronically charged nozzle to form the filament. Materials described as (b) and (c) above may be formed in this manner. The osteoinductive agent may be incorporated within the polymer, or within the polymer and ceramic composite during the formation of the filament. The osteoinductive agent may be soaked, sprayed, dipped, or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing durationof immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0167] Alternatively, the polymer may be dissolved in a solvent and the optional ceramic (preferably provided in particulate form) dispersed in the solvent, whereafter a mandrel may be dipped within the solution to create the filament. Materials described as (b) and (c) above may be formed in this manner. The osteoinductive agent may be incorporated within the polymer, or within the polymer and ceramic composite during the formation of the filament. The osteoinductive agent may be soaked, sprayed, dipped or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing duration of immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0168] Alternatively, polymer and polymer-ceramic composites may be 3-D printed using fused deposition modelling or direct ink writing to achieve the filament. Materials described as (b) and (c) above may be formed in this manner. The osteoinductive agent may be incorporated within the polymer, or within the polymer and ceramic composite during the formation of the filament. The osteoinductive agent may be soaked, sprayed, dipped or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing duration of immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0169] Alternatively, compression modelling of a heated polymer or polymer-ceramic material within a mold may be used to achieve the required filament shape. The temperature used is preferably sufficient to reach the Tg (glass transition temperature) for the polymer to allow the uniform incorporation of the osteoinductive agent. Such temperature ranges are known in the art. For example,a polymer such as PLGA may be heated to a temperature of from 30 to 100 °C, preferably a temperature of from 40 to90 °C, such as a temperature from 45 to 80 °C. Materials described as (b) and (c) above may be formed in this manner. The osteoinductive agent may be incorporated within the polymer, or within the polymer and ceramic composite during the formation of the filament. The osteoinductive agent may be soaked, sprayed, dipped or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing duration of immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0170] Alternatively, ceramic material may be prepared by methods known in the art, including but not limited to: extrusion, slip casting, robocasting, gel casting, isostatic pressing and machining. Materials described as (a) above may be formed in this manner. The osteoinductive agent may be soaked, sprayed, dipped or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing duration of immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0171] For materials, (a) and (c), to achieve attachment and / or tethering of the osteoinductive agent, the osteoinductive agent may be soaked, sprayed, dipped or otherwise coated onto the surface of the filament. For example, the filament may be immersed into a solution containing the osteoinductive agent. Increasing duration of immersion or soaking is known to increase the proportion of osteoinductive agent which is tethered or attached to the filament. The duration may be at least 1 minute, preferably 5 minutes, preferably 10 minutes, preferably 20 minutes.

[0172] The solid osteoinductive filament may be formed by extrusion, preferably hot melt extrusion. When forming by extrusion, the osteoinductive agent may beincorporated within a polymer, or within a polymer and ceramic composite. Materials described as (b) and (c) above may be formed in this manner.

[0173] Where the solid osteoinductive filament further comprises one or more optional component and / or surfactant, the one or more additional component(s) and / or surfactant may also be combined with the osteoinductive agent to form a mixture. Where the solid osteoinductive filament further comprises one or more optional component and / or surfactant, the one or more additional component(s) and / or surfactant may be incorporated, preferably encapsulated, within the polymer, or within the polymer and ceramic composite during the formation of the filament. For example, prior to extrusion, preferably hot melt extrusion.

[0174] If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot melt extrusion process may have a feed rate of 1 to 4%, such as 1 to 3%. The hot melt extrusion process may have a screw speed of 10 to 30 rpm. The skilled person will recognise that the hot melt extrusion parameters such as the feed rate may be adjusted for providing different filaments in accordance with the invention herein.

[0175] If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot-melt extrusion process may comprise heating and extruding a mixture of osteoinductive agent and polymer, or osteoinductive agent and polymer and ceramic, through the temperatures steps of 50 to 90°C, 70 to 110°C, 70 to 110°C, 70 to 110°C (each temperature representing a different step / section of extruder as the material passes through) optionally with a total time of 10 minutes or less.

[0176] If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot-melt extrusion process may comprise heating and extruding the mixture through the temperature steps of 60°C, 80°C, 80°C, 80°C (each temperature representing a different step / section of extruder as the material passes through) optionally with a total time of 10 minutes or less.If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot-melt extrusion process may not exceed 110°C and / or may not exceed 10 minutes.

[0177] If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot melt extrusion process may comprise the use of a blade with the settings of 1-6 m / min and 0.1 to 150 mm, preferably 0.5 to 70 mm, more preferably 3 m / min and 1 to 40 mm.

[0178] If the solid osteoinductive filament is formed by an extrusion process, such as hot melt extrusion, the hot-melt extrusion process conditions advantageously avoid significant heat damage to the osteoinductive agent.

[0179] If the solid osteoinductive filament further comprises a surfactant, the surfactant, such as poloxamer 407, may be used in the production of the osteoinductive filament in powder form, for example, as a micronized powder. The particles of surfactant, such as poloxamer, may be less than 105 pm in size. At least 85% of the poloxamer 407 particles may be less than 60pm in size, preferably less than 53pm in size.

[0180] The solid osteoinductive filament of the invention may be sterilised prior to use. Sterilisation may be by irradiation prior to or after packaging of the filament for transport and / or storage. Sterilisation may be carried out by irradiation of a sealed packaging comprising the filament. Preferably, the sealed packaging is gas-impermeable. The sealed packaging preferably comprises an oxygen scavenger and / or desiccant. The oxygen scavenger and / or desiccant may be provided in one or more gas-permeable packaging, such as a porous polyethylene, which may be sealed together with the filament within the gas-impermeable packaging. The filament may be protected from oxygen and / or free radicals during irradiation by such packaging.

[0181] Any sealed packaging for the filaments according to the present invention may be sealed in a low- or zero-oxygen environment, such as in a nitrogen environment. The sealed packaging may not comprise oxygen. The sealed packaging maycomprise nitrogen gas (instead of air). The sealed packaging may be sealed by vacuum packing, for example, drawn to about 2mbar of pressure.

[0182] The kit according to the fourth aspect of the present invention comprises: (i) the 3D-printed orthopaedic implant according to the first aspect of the present invention; and (ii) at least one solid osteoinductive filament according to the third aspect of the present invention.

[0183] The kit according to the fifth aspect of the present invention comprises: (i) the 3D-printed orthopaedic implant according to the second aspect of the present invention; and (ii) at least one solid osteoinductive filament according to the third aspect of the present invention.

[0184] Accordingly, all features, whether preferred or otherwise, of the 3D-printed orthopaedic implants of the first or second aspects of the present invention, and of the solid osteoinductive filament according to the third aspect of the present invention, are applicable to the 3D-printed orthopaedic implant and solid osteoinductive filament (components (i) and (ii)) of the kit according to the fourth and fifth aspects of the present invention.

[0185] The kit according to the fourth or fifth aspect of the present invention may further comprise additional 3D-printed orthopaedic implants of differing dimensions (in addition to component (i)), such that, at the point of use, the surgeon can decide which implant is of the appropriate size for the subject in need. The additional 3D-printed orthopaedic implants are preferably implants according to the first and / or second aspect of the present invention.

[0186] The solid osteoinductive filament (component (ii)) of the kit according to the fourth or fifth aspect of the present invention will preferably complement at least one hollow discrete tunnel of the implant. This may be with respect to, for example, dimensions such as length and width, and features such as cross-section or cross-sectional shape.

[0187] Preferably, for the kit according to the fourth or fifth aspect of the present invention, the at least one solid osteoinductive filament (component (ii)) does not extendbeyond the opening of the discrete hollow tunnel of the 3D-printed orthopaedic implant into which it can be inserted. Preferably, one filament, such as two or more, or three or more, or four or more, more preferably each of the filaments, does not extend beyond the opening of a tunnel into which it can be inserted.

[0188] Preferably, for the kit according to the fourth or fifth aspect of the present invention, the length of the at least one solid osteoinductive filament (component (ii)) is smaller than that of the discrete hollow tunnel of the 3D-printed orthopaedic implant (component (i)) into which it is operable to be inserted. Preferably, the length of one filament, such as two or more, or three or more, or four or more, more preferably each of the filaments, is smaller than that of the discrete hollow tunnel of the 3D-printed orthopaedic implant (component (i)) into which it is operable to be inserted.

[0189] Preferably, for the kit according to the fourth or fifth aspect of the present invention, the width of the at least one solid osteoinductive filament (component (ii)) is smaller than that of the discrete hollow tunnel of the 3D-printed orthopaedic implant (component (i)) into which it is operable to be inserted. Preferably, the width of one filament, such as two or more, or three or more, or four or more, more preferably each of the filaments, is smaller than that of the discrete hollow tunnel of the 3D-printed orthopaedic implant (component (i)) into which it is operable to be inserted.

[0190] Preferably, the kit according to the fourth or fifth aspects of the present invention comprises a plurality (two or more) of solid osteoinductive filaments (component (ii)). Preferably, the kit comprises two or more solid osteoinductive filaments, such as three or more, or four or more solid osteoinductive filaments. Preferably, these are solid osteoinductive filaments according to the third aspect of the present invention. The solid osteoinductive filaments may be the same or different. This is as described herein for each feature of the filament according to the third aspect of the present invention, e.g. length, width and cross-sectional shape. The features of each filament may be independently selected. Preferably, the at least one solid osteoinductive filament provided in the kit according to the fourth or fifth aspect of the present invention compliments the at least one discrete hollow tunnelof the implant. Preferably, each of the solid osteoinductive filaments provided in the kit according to the fourth or fifth aspect of the present invention compliment at least one discrete hollow tunnel of the implant.

[0191] Preferably, the kit according to the fourth or fifth aspect of the present invention provides at least a number of solid osteoinductive filaments (component (ii)) to fill the majority of discrete hollow tunnels in the 3D-printed orthopaedic implant (component (i)).

[0192] Preferably, the kit according to the fourth or fifth aspect of the present invention provides at least the same number of solid osteoinductive filaments (component (ii)) as the number of discrete hollow tunnels in the 3D-printed orthopaedic implant (component (i)). However, as noted below, for use, not every discrete hollow tunnel of the implant has to contain a solid osteoinductive filament.

[0193] For the kit according to the fourth or fifth aspect of the present invention, the components (i) and (ii) may be provided separately or together. The components (i) and (ii) may be provided in packaging, preferably separate packaging. The packaging is preferably sealed. Preferably, the components (i) and (ii) do not contact one another in the kit.

[0194] For the kit according to the fourth or fifth aspect of the present invention, if solid osteoinductive filaments are provided in different sizes, for examples of different lengths, they may be provided in the same or separate packaging, preferably separate packaging.

[0195] For the kit according to the fourth or fifth aspect of the present invention, if the kit comprises additional implants as described above, the additional implants may be provided in the same or separate packaging, preferably separate packaging.

[0196] The kit according to the fourth or fifth aspect of the present invention may comprise at least one additional solid osteoinductive filament(s) operable to be inserted into the additional implant(s). The at least one additional solid osteoinductive filament(s) are preferably according to the third aspect of the present invention.The at least one solid osteoinductive filament (component (ii))of the kit according to the fourth or fifth aspect of the present invention, may be provided in the same or different packaging to, if present, any additional solid osteoinductive filament(s) as described above.

[0197] Where the kit provides a plurality (two or more) of solid osteoinductive filaments (component (ii)), and the filaments are formed from different materials, e.g. (a), (b) or (c) as detailed above, the filaments may be provided in the same or different packaging depending on the composition (a), (b) or (c) of the filament, preferably different packaging.

[0198] Where the kit provides a plurality (two or more) of solid osteoinductive filaments (component (ii)), and the filaments are of different length and / or width, the filaments may be provided in the same or different packaging depending on the length and / or width of the filament.

[0199] Preferably, when the at least one solid osteoinductive filament (component (ii)) is provided in separate packaging, the packaging is sealed. Preferably, when the at least one solid osteoinductive filament (component (ii)) is provided in separate packaging, the packaging is gas-impermeable.

[0200] Preferably, when the at least one solid osteoinductive filament (component (ii)) is provided in separate packaging, the packaging comprises an oxygen scavenger and / or desiccant. The oxygen scavenger and / or desiccant may be provided in one or more gas-permeable packaging, such as a porous polyethylene, which may be sealed together with the filament within the gas-impermeable packaging. The filament may be protected from oxygen and / or free radicals during irradiation by such packaging. The sealed packaging may not comprise oxygen. The sealed packaging may comprise nitrogen gas (instead of air).

[0201] The kit may further comprise an oxygen scavenger and / or desiccant. If so, the oxygen scavenger and / or desiccant is preferably in packaging containing component (ii). The skilled person will be familiar with suitable oxygen scavengers sufficient to maintain a substantially oxygen free environment. The oxygenscavenger may at least absorb more than 20 ml oxygen within 7 days under 25±2°C. Alternatively, the oxygen scavenger may at least absorb more than 40 ml oxygen within 7 days under 25±2°C. Example oxygen scavengers may comprise one or more, or all of, silicide, carbon hydride compound, resin powder, activated carbon, silica gel, and inorganic additives. The skilled person will be familiar with suitable desiccants sufficient to maintain low moisture content. The desiccant may have an adsorption capacity of at least = > 16.5% at 25 °C, 80% relative humidity.

[0202] Preferably, the kit according to the fourth or fifth aspect of the present invention does not comprise a bone harvested material, from either the patient (autograft) or a separate bone tissue donor (allograft, demineralised bone matrix, demineralised bone fibres, cellular bone grafts).

[0203] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention and at least one solid osteoinductive filaments according to the third aspect of the present invention, or the kit according to the fourth or fifth aspect of the present invention, may be used to form the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention.

[0204] Accordingly, all features, whether preferred or otherwise, of the 3D-printed orthopaedic implants of the first or second aspects of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, or the kit according to the fourth or fifth aspect of the present invention, are applicable to the 3D-printed orthopaedic implant according to the sixth and seventh aspects of the present invention.

[0205] Accordingly, the sixth aspect of the present invention comprises a 3D-printed orthopaedic implant according to the first aspect of the present invention having a solid osteoinductive filament according to the third aspect of the present invention inserted in a discrete hollow tunnel thereof. At least one discrete hollow tunnel of the 3D-printed orthopaedic implant according to the first aspect of the present invention contains a solid osteoinductive filament according to the third aspect of the present invention. The sixth aspect of the present invention comprises the kit according to the fourth aspect of the present invention, at least one solidosteoinductive filament having been inserted into a discrete hollow tunnel of the 3D-printed orthopaedic implant.

[0206] The seventh aspect of the present invention comprises a 3D-printed orthopaedic implant according to the second aspect of the present invention having a solid osteoinductive filament according to the third aspect of the present invention inserted in a discrete hollow tunnel thereof. At least one discrete hollow tunnel of the 3D-printed orthopaedic implant according to the second aspect of the present invention contains a solid osteoinductive filament according to the first aspect of the present invention. The seventh aspect of the present invention comprises the kit according to the fifth aspect of the present invention, at least one solid osteoinductive filament having been inserted into a discrete hollow tunnel of the 3D-printed orthopaedic implant.

[0207] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention and at least one solid osteoinductive filament according to the third aspect of the present invention, or the kit according to the fourth or fifth aspect of the present invention, may be used to form the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention at the point of surgery or treatment. This may be by an orthopaedic practitioner such as a surgeon.

[0208] If there is more than one discrete hollow tunnel, not all the discrete hollow tunnels of the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention of the implant may be filled with a solid osteoinductive filament, but preferably the majority of the discrete hollow tunnels of the implant contain a solid osteoinductive filament. More preferably, for the implant according to the sixth or seventh aspect of the present invention, each discrete hollow tunnel (all discrete hollow tunnels) of the implant contains a solid osteoconductive filament.

[0209] Preferably, for the implant according to the sixth or seventh aspect of the present invention, a discrete hollow tunnel contains one to three filaments, such as one or two filaments therein, or two. Most preferably, a discrete hollow tunnel containsa single filament. For the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, one to three filament(s) may be introduced into a discrete hollow tunnel, preferably two, and most preferably, only one filament is introduced into a discrete hollow tunnel. Preferably, two discrete hollow tunnels, such as three or more, or four or more, more preferably each discrete hollow tunnel, contains one to three filaments, preferably one or two, such as two, and preferably only one filament therein.

[0210] Preferably, for the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, a solid osteoinductive filament is contained in the majority of the discrete hollow tunnels, more preferably a single solid osteoinductive filament is contained in the majority of the discrete hollow tunnels. More preferably, a solid osteoinductive filament is contained in each discrete hollow tunnel (all of the discrete hollow tunnels) of the implant, or a solid osteoinductive filament is contained in each discrete hollow tunnel (all of the discrete hollow tunnels) of the implant.

[0211] Each filament of the present invention is preferably a distinct, individual entity with respect to any other filament.

[0212] It will be appreciated that, in the 3D-printed orthopaedic implant according to the fourth or fifth aspects of the present invention, the solid osteoinductive filament(s) will preferably complement the discrete hollow tunnel(s) in which they are contained. This may be with respect to, for example, dimensions such as length and width, and features such as cross-section or cross-sectional shape.

[0213] Preferably, the solid osteoinductive filament(s) does not extend beyond the opening of the tunnel(s) in which it is contained.

[0214] Preferably, for the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, the at least one solid osteoinductive filament does not extend beyond the opening of the discrete hollow tunnel in which it is contained. Preferably, the filament, such as two or more, or three or more, or fouror more, more preferably each of the filaments, does not extend beyond the opening of the discrete hollow tunnel in which it is contained.

[0215] Preferably, for the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, the length of the at least one solid osteoinductive filament is smaller than that of the discrete hollow tunnel in which it is contained. Preferably, the length of the filament, such as two or more, or three or more, or four or more, more preferably each of the filaments, is smaller than that of the discrete hollow tunnel in which it is contained.

[0216] Preferably, for the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, the width of the at least one solid osteoinductive filament is smaller than that of the discrete hollow tunnel in which it is contained. Preferably, the width of the filament, such as two or more, or three or more, or four or more, more preferably each of the filaments, is smaller than that of the discrete hollow tunnel in which it is contained.

[0217] Preferably, the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention comprises a plurality (two or more) of solid osteoinductive filaments contained therein. Preferably, the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention comprises two or more osteoinductive filaments, such as three or more, or four or more osteoinductive filaments, contained therein. More preferably, the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention comprises a plurality (e.g. two or more, three or more, or four or more) of solid osteoinductive filaments contained therein and each of the plurality of solid osteoinductive filaments are contained in a different discrete hollow tunnel. A single solid osteoinductive filament is preferably contained in a single discrete hollow tunnel.

[0218] Preferably, the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention contains the same number of solid osteoinductive filaments as the number of discrete hollow tunnels.For the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, it will be appreciated that the porosity of the implant is lower than the 3D-printed orthopaedic implant according to the first or second aspect of the present invention. For the 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention, the implant preferably has a porosity of at least 55%, such as at least 50%, or at least 45%, such as at least 40%, or 40%. The implant may have a porosity of from 40 to 100%, such as from 45 to 100% or from 50 to 100%, or from 55 to 100%. This may be measured as defined herein.

[0219] For the implant according to the sixth or seventh aspect of the present invention, for the discrete hollow tunnel(s) having filament(s) contained therein, the filaments(s), preferably a single filament, may occupy at least 70% of the volume of the discrete hollow tunnel in which it is contained. This enables the filament to be more easily retained therein. This may be measured using micro-CT imaging as defined herein. The filaments(s), preferably a single filament, may occupy from 70% to 98% of the volume of the discrete hollow tunnel in which it is contained, such as from 80% to 95%.

[0220] In use, the kit according to the fourth or fifth aspect of the present invention, or the implant according to the sixth or seventh aspect of the present invention, preferably provides a total dose of the osteoinductive agent of 0.0002 to 12 mg, more preferably 0.002 to 10 mg, or 0.1 to 8 mg, such as 1 to 6 mg to the subject in need. Preferably, the total dose of the osteoinductive agent is from 0.05 mg to 4 mg, more preferably from 0.2 mg to 2 mg per 3D-printed orthopaedic implant. This is the total dose per 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention. Such doses are considered to be ‘effective’ amounts’ or ‘therapeutically effective amounts’. This is the amount required to achieve a desired pharmacologic effect or therapeutic improvement without undue adverse side effects. In this case, it is an amount require to facilitate bone formation and / or bone fusion, to achieve bone healing. It is understood that "an effective amount" or "a therapeutically effective amount" can vary from subject to subject, depending on the age, weight, general condition of the individual, modeof administration, the orthopaedic application or orthopaedic condition being treated, and severity thereof, as well as other factors.

[0221] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in a method of promoting bone fusion and / or bone formation, preferably spinal bone formation and / or spinal bone fusion, according to the eighth or ninth aspects of the present invention.

[0222] Optionally, for the ninth aspect of the present invention, the 3D-printed orthopaedic implant may be sterilised (as described herein) prior to inserting the at least one solid osteoinductive filament into a discrete hollow tunnel, i.e. prior to step (i) of the ninth aspect of the present invention.

[0223] Optionally, for the ninth and tenth aspects of the present invention, attachment or anchor means such as screws and plates may be used (in step (ii) of the ninth aspect, and step (i) of the tenth aspect) to hold the implant in place in the body to prevent movement or migration of the implant.

[0224] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in any clinical practice or treatment. For example, it may be used in hospital settings.

[0225] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used for any orthopaedic application including, but not limited to, foot and ankle implants,craniomaxillofacial, dental, long bone implants, extremity implants, bone implants for bone fusion and / or formation, spinal implants for spinal fusion, and joint implants. ‘Long bones’ are as known in the art, and are typically characterised by their elongated shape, of longer length than width. They typically have a central shaft and two expanded ends. Examples of long bones include, but are not limited to: femur, tibia, fibula, humerus, ulna, and radius.

[0226] Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention is used as, or for, bone implants for bone fusion and / or formation, such as for spinal implant and / or fusion procedure or craniofacial work relating to the jaw and / or associated dental work. Preferably, the 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention is fabricated for bone fusion procedures, such as spinal fusion procedures.

[0227] In particular, the present invention is preferably used for spinal implants and / or spinal fusion procedures. With respect to implants for spines, intervertebral (interbody), intervertebral (intrabody), and vertebral implants may be fabricated. Interbody devices that sit between vertebra in the spine for spinal fusion procedures.

[0228] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may therefore be used as a bone implant and / or bone tissue scaffold, preferably a spinal implant such as a spinal fusion implant, and more preferably a spinal interbody fusion implant. Spinal fusioninvolves inserting the implant between vertebrae, in place of the normal intervertebral disc.

[0229] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in a spinal interbody fusion procedure.

[0230] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in a spinal interbody fusion procedure include TLIF (transforaminal lumbar interbody fusion) procedures, XLIF (extreme lateral interbody fusion) procedures, PLIF (posterior lumbar interbody fusion) procedures, lateral implant procedures, OLID (oblique lateral interbody fusion) procedures, ACDF (anterior cervical discectomy and fusion) procedures, OCF (occipitocervical fusion) procedures, PCF (posterior cervical fusion) procedures, and ALIF (anterior lumbar interbody fusion) procedures. Preferably, for anterior Lumbar Interbody (ALIF) fusion procedure.

[0231] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in bone grafting or repair to augment the grafting of natural bone from the subject or from a donor.

[0232] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth orseventh aspect of the present invention may be used to fill a space in a subject’s bone, such as a damaged bone. The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in any bone grafting fusion procedure.

[0233] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in spinal fusion, including TLIF (transforaminal lumbar interbody fusion), XLIF (extreme lateral interbody fusion), PLIF (posterior lumbar interbody fusion), OLID (oblique lateral interbody fusion), ACDF (anterior cervical discectomy and fusion), OCF (occipitocervical fusion), PCF (posterior cervical fusion), and ALIF (anterior lumbar interbody fusion). Preferably, for anterior Lumbar Interbody (ALIF) fusion.

[0234] The 3D-printed orthopaedic implant according to the first or second aspect of the present invention, the solid osteoinductive filament according to the third aspect of the present invention, the kit according to any of the fourth or fifth aspect of the present invention, and 3D-printed orthopaedic implant according to the sixth or seventh aspect of the present invention may be used in the treatment of idiopathic scoliosis, neuromuscular scoliosis, degenerative disc disease, spondylosis, spondylolisthesis, or any other condition that may be treated by bone repair, bone grafting, or bone replacement.

[0235] As used herein, the term “disease” is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is used broadly to encompass any disorder, illness, abnormality, pathology, sickness, condition or syndrome in which physiological function is impaired irrespective of the nature of the aetiology (or indeed whether the aetiological basisfor the disease is established). It therefore encompasses conditions arising from trauma, injury, surgery, radiological ablation, poisoning or nutritional deficiencies.

[0236] As used herein, the term "treatment" or "treating" refers to an intervention (e.g. the administration of an agent to a subject) which cures, ameliorates or lessens the symptoms of a disease or removes (or lessens the impact of) its cause(s) (for example, the causative microbes such as bacterium). In this case, the term is used synonymously with the term “therapy”. Thus, the treatment according to the invention may be characterized by bone formation and / or bone fusion achieved using the 3D-printed orthopaedic implant, solid osteoinductive filaments, or kit according to any of the first to fourth aspects of the present invention. Thus, the present invention find application in methods of healing bone, in particular through bone formation and / or bone fusion.

[0237] The present invention advantageously enables localised delivery of targeted therapy. By ‘localised’ as used herein is meant the restricted to a particular place or part of the body of the subject.

[0238] It will be appreciated that depending on the orthopaedic injury or condition being treated, at least the osteoinductive agent type, amount of osteoinductive agent, and selection of the material from which the filament is formed may be altered so as to modify and optimise the release profile of the osteoinductive agent to suit the patient and treatment need.

[0239] The 3D-printed orthopaedic implant, solid osteoinductive filament, or kit according to any of the aspects of the present invention may be administered to a subject in need. The term "subject" (which is to be read to include "individual", "animal", "patient" or "mammal" where context permits) defines any subject, particularly a mammalian subject, for whom treatment is indicated. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, andtigers; equids such as horses, donkeys, and zebras; food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; rodents such as mice, rats, hamsters and guinea pigs; and so on. Preferably, the subject is a human.

[0240] All of the features contained herein may be combined with any of the above aspects in any combination.

[0241] All references to particular chemical compounds herein are to be interpreted as covering the compound perse, and also, where appropriate, derivatives, hydrates, solvates, complexes, isomers and tautomers thereof.

[0242] For a better understanding of the invention and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example, to the accompanying drawings, in which:

[0243] Figures 1 to 7 are intended to depict example 3D-printed orthopaedic implants according to the first or second aspect of the present invention, and the solid osteoinductive filaments according to the third aspect of the present invention, in a simple, stylised manner. They represent simplified versions of the implant and filaments so as to support the understanding of the present invention when read alongside the description.

[0244] Figure 1 shows solid osteoinductive filaments 101a and 101b according to the third aspect of the present invention. Each of the filaments 101a and 101b independently has a length that is three times its width. Although the filaments 101a and 101b are shown as being substantially circular in cross-section, the cross-section of each filament 101a and 101b may vary. Each of the filaments 101a and 101b may be formed of the same or different material (a), (b) or (c), preferably material (b).

[0245] Figures 2 to 7 show 3D-printed orthopaedic implants according to the first or second aspect of the present invention.Figures 2 and 3 respectively show an isometric and side view of a 3D-printed orthopaedic implant 201 according to the first or second aspect of the present invention. The 3D-printed orthopaedic implant 201 has a porous osteoconductive scaffold 203 and one or more non-porous support portion 205. The 3D-printed orthopaedic implant 201 has five discrete hollow tunnels 207a, 207b, 207c, 207d and 207e. The discrete hollow tunnels are distributed throughout the implant 201 and operable to have a solid osteoinductive filament according to the present invention inserted therein. The implant 201 has a porosity of at least 60%. The porous osteoconductive scaffold 203 of the implant 201 is at least 60% of the volume of the implant 201. Each discrete hollow tunnel 207a, 207b, 207c, 207d and 207e has a volume of 7% or less of the implant 201. Each discrete hollow tunnel 207a, 207b, 207c, 207d and 207e has a substantially uniform cross-section. This is depicted as substantially circular, but each discrete hollow tunnel 207a, 207b, 207c, 207d and 207e may have any cross-sectional shape. Each discrete hollow tunnel 207a, 207b, 207c, 207d, and 207e has a length that is at least three times its width. The discrete hollow tunnels 207a, 207b, 207c, 207d, 207e extend into the porous osteoconductive scaffold 203 at different directions, and at different angles to an exterior surface(s) of the implant 201. Each discrete hollow tunnels 207a, 207b, 207c, 207d, 207e has an independently selected length. Although each discrete hollow tunnel 207a, 207b, 207c, 207d, 207e has the same width, each width may be independently selected, and may be different or the same. Discrete hollow tunnel 207a extends completely through the implant 201. Discrete hollow tunnels 207b, 207c, 207d and 207e are blind-end tunnels. With the side view of Figure 3, the implant 201 is shown as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.

[0246] Figures 4 and 5 respectively show an isometric and side view of a 3D-printed orthopaedic implant 301 according to the first or second aspect of the present invention. The 3D-printed orthopaedic implant 301 has a porous osteoconductive scaffold 303 and one or more non-porous support portion 305. The 3D-printed orthopaedic implant 301 has three discrete hollow tunnels 307a, 307b, and 307c. The discrete hollow tunnels are distributed throughout the implant 301 and operable to have a solid osteoinductive filament according to the present inventioninserted therein. The implant 301 has a porosity of at least 60%. The porous osteoconductive scaffold 303 of the implant 301 is at least 60% of the volume of the implant 201. Each discrete hollow tunnel 307a, 307b, and 307c has a volume of 7% or less of the implant 301. Each discrete hollow tunnel 307a, 307b, and 307c has a substantially uniform cross-section. This is substantially circular. This is depicted as substantially circular, but each discrete hollow tunnel 307a, 307b, and 307c may have any cross-sectional shape. Each discrete hollow tunnel 307a, 307b, and 307c has a length that is at least three times its width. The discrete hollow tunnels 307a, 307b, and 307c extend into the porous osteoconductive scaffold 303 at different directions, and at different angles to an exterior surface(s) of the implant 301. Each discrete hollow tunnels 307a, 207b, and 307c has an independently selected length. Although each discrete hollow tunnel 307a, 307b, and 307c, has the same width, each width may be independently selected, and may be different or the same. Discrete hollow tunnel 307a extends completely through the implant 201. Discrete hollow tunnels 307b and 307c are blind-end tunnels. The implant 301 has a central graft chamber 309. The central graft chamber 309 has a volume of 30% or more of the implant 301. With the side view of Figure 5, the implant 301 is shown as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.

[0247] Figures 6 and 7 respectively show an isometric and side view of a 3D-printed orthopaedic implant 401 according to the first or second aspect of the present invention. The 3D-printed orthopaedic implant 401 has a porous osteoconductive scaffold 403 and one or more non-porous support portion 405. The 3D-printed orthopaedic implant 401 has three discrete hollow tunnels 407a, 407b, and 407c. The discrete hollow tunnels are distributed throughout the implant 401 and operable to have a solid osteoinductive filament according to the present invention inserted therein. The implant 401 has a porosity of at least 60%. The porous osteoconductive scaffold 403 of the implant 401 is at least 60% of the volume of the implant 201. Each discrete hollow tunnel 407a, 407b, and 407c has a volume of 7% or less of the implant 401. Each discrete hollow tunnel 407a, 407b, and 407c has a substantially uniform cross-section. This is substantially circular. This is depicted as substantially circular, but each discrete hollow tunnel 407a, 407b,and 407c may have any cross-sectional shape. Each discrete hollow tunnel 407a, 407b, and 407c has a length that is at least three times its width. The discrete hollow tunnels 407a, 407b, and 407c extend into the porous osteoconductive scaffold 403 at different directions, and at different angles to an exterior surface(s) of the implant 401. Each discrete hollow tunnels 407a, 407b, and 407c has an independently selected length. Although each discrete hollow tunnel 407a, 407b, and 407c, has the same width, each width may be independently selected, and may be different or the same. Discrete hollow tunnel 407a extends completely through the implant 401. Discrete hollow tunnels 407b and 407c are blind-end tunnels. With the side view of Figure 7, the implant 401 is shown as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.

[0248] Measurement Methods

[0249] Micro-CT Imaging

[0250] The method utilises micro-CT imaging to acquire volumetric data, followed by computational segmentation and analysis to differentiate between different material regions of the 3D-printed orthopaedic implant, for example, the porous osteoconductive scaffold, a non-porous support portion, and the at least one discrete hollow tunnel (and optional central graft chamber). The method defines the different regions with respect to a predetermined density threshold. For example, the non-porous solid portion is defined as a continuous material phase with a density above a predetermined threshold, whereas the porous osteoconductive scaffold is defined as a pore-containing structure with a density below the predetermined threshold, and the at least one discrete hollow tunnel is defined as an extended region with a length at least three time its width with a density below the predetermined threshold. If a central graft chamber is present, this may be defined as an extended region of larger width than the tunnels extending completely through the implant with a density below the predetermined threshold. The method enables accurate volume fraction computation, surface area analysis, and distance measurements such as length and width of the implant and features thereof, e.g. discrete hollow tunnels.The different regions of the implant exhibit a grey scale intensity within the micro-CT dataset that corresponds to a density exceeding a predetermined threshold (for the non-porous support portion), or below a predetermined threshold (for the porous osteoconductive scaffold, and at least one discrete hollow tunnel with and optional central graft chamber), indicating the presence of the different regions. For the porous osteoconductive scaffold, and at least one discrete hollow tunnel (and optional central graft chamber), their structure is used to differentiate therebetween.

[0251] A micro-CT scanner with a resolution of at least 5-10 pm per voxel is used, in addition to image processing and segmentation software (e.g., Avizo, Imaged, Dragonfly, or Mimics), and computational analysis tools (e.g., MATLAB, Python, or Imaged plugins).

[0252] To prepare a sample for micro-CT imaging: (1 ) ensure the implant is clean and dry to prevent imaging artifacts; (2) secure the implant in a fixed position within the scanning chamber to minimize motion-induced distortions; and (3) if necessary, apply a radiopaque contrast agent to enhance the differentiation of the different regions.

[0253] One or more of the following parameters may be used: set the scanning resolution to 5-10 pm per voxel to capture fine structural details; adjust X-ray energy and exposure time to maximize contrast between the different regions; and use multiple projections (typically 1000-2000) to ensure high-fidelity reconstruction.

[0254] Image Processing and Segmentation involves:

[0255] (a) Reconstruction: Convert raw projection images into a 3D volumetric dataset using manufacturer-provided reconstruction software.

[0256] (b) Filtering and Noise Reduction: Apply Gaussian or median filters to reduce noise while preserving edges.(c) Thresholding: Utilise a predefined grayscale intensity threshold to differentiate the different regions (high-density and low-density greyscale values).

[0257] (d) Region Growing or Manual Segmentation: Use automated regiongrowing algorithms to refine segmentation of the different regions. Alternatively, manually adjust segmentation masks for accuracy.

[0258] (e) Morphological Analysis: Remove noise pixels using morphological operations (e.g., opening and closing). Validate segmentation accuracy by comparing with known reference structures or prior CAD models.

[0259] Volume: Micro CT-lmaging

[0260] Volume Calculation can then be calculated for each segmented region using:

[0261] V — N X Vvoxel

[0262] where N is the number of voxels classified for a region, and VVOxei is the volume of a single voxel. The percentage volume of a region, e.g. non-porous support portion, osteoconductive porous scaffold, or at least one discrete hollow tunnel (and optional central graft chamber), relative to the total volume can then be calculated using:

[0263] (1) %VX= VX / TX 100%VY= VyA / Tx 100%Vz = VZA / Tx 100; or

[0264] (2) %VX= VX / TX 100%VY= VyA / Tx 100;

[0265] where Vxrepresents the volume of the porous osteoconductive scaffold, VYrepresents the volume of the at least one discrete hollow tunnel (and optional central graft chamber), Vzrepresents the volume of the non-porous support portion, and VTrepresents the volume of the implant as a whole. Formula (2) may be used where the implant does not comprise a non-porous support portion.

[0266] For the volume of each of the discrete hollow tunnel(s), or central graft chamber, the reconstructed 3D dataset is analyzed using image processing software (Avizo,Dragonfly, Mimics, or ImageJ). A grayscale intensity thresholding method, such as that outlined above, is applied to distinguish the different regions of the implant. The discrete hollow tunnels, or optional central graft chamber, are distinguished from the porous structure of the porous osteoconductive scaffold using morphological operations (e.g., region-growing algorithms) to exclude pores / voids within the porous structure which do not form the continuous tunnels.

[0267] The segmented tunnel regions may be converted into a 3D binary mask, isolating the discrete tunnel, or optional central graft chamber.

[0268] The volume is computed by voxel integration, where:

[0269] • Each voxel (3D pixel) in the segmented mask represents a known physical volume (based on scan resolution).

[0270] • The total volume of the tunnel is determined by summing the volumes of all included voxels.

[0271] For enhanced accuracy, surface meshing techniques (STL format) can be used to refine the tunnel boundaries before performing numerical volume integration. The tunnel, or optional central graft chamber, can be visualized in cross-section to confirm continuity and connectivity using multi-slice viewing tools. If needed, a color-coded 3D map can be generated to illustrate volume distribution and variations along the tunnel’s length.

[0272] Surface Area: Micro-CT Imaging

[0273] To determine the external surface area of the implant, the following steps can be performed:

[0274] 1. Micro-CT Scanning: The implant is scanned using micro-CT at a suitable resolution, ensuring that fine surface details are captured. The resulting scan generates a 3D volumetric dataset, typically in DICOM or TIFF format.2. Segmentation of the External Surface: Image processing software is used to differentiate the implant from the surrounding background based on grayscale intensity values. A thresholding algorithm is applied to isolate the implant’s external surface.

[0275] 3. Surface Reconstruction and Mesh Generation: The segmented data is converted into a 3D surface mesh, commonly in STL (stereolithography) format, using software such as Avizo, Dragonfly, or Mimics.

[0276] 4. Surface Area Calculation: The surface area of the 3D mesh is computed using numerical methods, such as triangular tessellation, in software tools like MeshLab or MATLAB. If required, regional surface areas can be analyzed by defining specific zones on the implant.

[0277] The identification and calculation of the volume of the discrete tunnels may be performed as follows:

[0278] The implant is scanned using micro-CT imaging at a high resolution to capture both the external structure, internal structure and any internal voids, tunnels, or cavities.

[0279] Due to the higher density of the material of the medical implant, optimal X-ray energy settings are selected to ensure sufficient penetration while minimizing artifacts such as beam hardening. The scan produces a series of 2D projection images, which are reconstructed into a 3D volumetric dataset (DICOM, TIFF, or RAW format).

[0280] Depth of Implant: Micro-CT Imaging

[0281] 1. Scan the Implant: Position the implant in the micro-CT scanner and acquire high-resolution 3D imaging data, ensuring full coverage of its geometry.

[0282] 2. Reconstruct the 3D Model: Process the scan data using reconstruction software to create a voxel-based 3D model of the implant.3. Segment Structural Features: Apply density thresholding to differentiate the implant from any surrounding void spaces, ensuring clear boundary identification, and / or apply density thresholding to differentiate between different regions of the implant (as discussed above) including any inserted components (filaments) based on X-ray attenuation values.

[0283] 4. Measure Implant Depth: Use the analysis software’s measurement tools to determine the longest continuous dimension of the implant or filament from end to end (distance from front (of subject) to back (of subject) of the implant as it is typically positioned when in use in a subject, for example, in spinal implant and / or procedures).

[0284] Height of Implant: Micro-CT Imaging

[0285] 1. Scan the Implant: Position the implant in the micro-CT scanner and acquire high-resolution 3D imaging data, ensuring full coverage of its structure.

[0286] 2. Reconstruct the 3D Model: Process the scan data using reconstruction software to generate a voxel-based 3D model of the implant.

[0287] 3. Segment Structural Features: Apply density thresholding to differentiate the implant from any surrounding void spaces, ensuring clear boundary identification.

[0288] 4. Measure Height at Multiple Points: Select several reference points across the implant surface and measure the vertical distance from the top surface to the lowest point along the z-axis (height). If the distance varies (e.g., due to a slope), sample measurements at regular intervals along the implant. The height of the implant refers to the average (mean) distance from top (superior - closer to head) to bottom (inferior - closer to feet) of the implant as it is typically positioned when in use in a subject, for example in spinal implant and / or fusion procedures.5. Calculate the Average Height: Compute the average height by summing all measured heights and dividing by the number of measurement points:

[0289] Average Height = (total height measurements / number of height measurements)

[0290] This accounts for variations in height and provides a representative value. The average accounts for differing lordotic angles, where the higher is lower at the front and higher at the back, for example, when the implant is used in spinal fusion procedures.

[0291] 6. Verify and Export Data: Cross-check measurements, refine segmentation if necessary, and export results for further analysis or comparison with design specifications.

[0292] Length of Discrete Hollow Tunnel(s) & Solid Osteoinductive Filament(s): Micro-CT Imaging

[0293] 1. Scan the Implant or Filament: Position the implant orfilament in the micro- CT scanner and acquire high-resolution 3D imaging data, ensuring full coverage of its geometry.

[0294] 2. Reconstruct the 3D Model: Process the scan data using reconstruction software to create a voxel-based 3D model of the implant orfilament.

[0295] 3. Segment Structural Features: Apply density thresholding to differentiate between different regions of the implant (as discussed above) including any inserted components (filaments) based on X-ray attenuation values.

[0296] 4. Measure Filament Length: Use the analysis software’s measurement tools to determine the longest continuous dimension of the filament from end to end.

[0297] 5. Identify and Measure Tunnel(s) Length: Detect discrete hollow tunnel(s) by identifying elongated low-density regions and measure their length.6. Detect and Quantify Solid Inserts: Locate any solid filaments inserted within a tunnel(s) by segmenting higher-density regions and measuring their position, volume, and length relative to the tunnel dimensions.

[0298] 7. Verify and Export Data: Cross-check all measurements, refine segmentations if necessary, and export results for further analysis or comparison with design specifications.

[0299] Steps 1 to 3 and 7 are required. Which of one or more of steps 4 to 6 are included depends upon the desired measurement.

[0300] Step 4 provides measurement of the length of a solid osteoinductive filament according to the third aspect of the present invention.

[0301] Step 5 provides measurement of the length of a discrete hollow tunnel(s) of a 3D-printed orthopaedic implant according to any of the first, second, fourth, fifth, sixth, or seventh aspect of the present invention.

[0302] Step 6 provides measurement of the length of a filament according to the third aspect of the present invention within a discrete hollow tunnel(s) of a 3D-printed orthopaedic implant according to any of the first, second, fourth, fifth, sixth, or seventh aspect of the present invention.

[0303] Width of Implant, Discrete Hollow Tunnel(s), & Solid Osteoinductive Filament(s): Micro-CT Imaging

[0304] 1. Scan the Implant or Filament: Position the implant orfilament in the micro- CT scanner and acquire high-resolution 3D imaging data, ensuring full coverage of its geometry.

[0305] 2 Reconstruct the 3D Model: Process the scan data using reconstruction software to create a voxel-based 3D model of the implant or filament.3. Segment Structural Features: Apply density thresholding to differentiate between different regions of the implant (as discussed above) including any inserted components (filaments) based on X-ray attenuation values.

[0306] 4. Measure Implant or Filament Width: Use the analysis software’s measurement tools to determine the width (widest continuous dimension) of the implant or width of a filament. As referred to herein, the width of the implant refers to the distance from side to side (laterally) of the implant as it is typically positioned when in use in a subject, for example, in spinal implant and / or fusion procedures.

[0307] 5. Identify and Measure Hollow Width: Detect discrete hollow tunnel(s) by identifying elongated low-density regions and measure their width.

[0308] 6. Detect and Quantify Solid Inserts: Locate any solid filaments within a tunnel(s) by segmenting higher-density regions and measuring their position, volume, and width relative to the tunnel dimensions.

[0309] 7. Verify and Export Data: Cross-check all measurements, refine segmentations if necessary, and export results for further analysis or comparison with design specifications.

[0310] Steps 1 to 3 and 7 are required. Which of steps 4 to 6 are used depends upon the desired measurement.

[0311] Step 4 provides measurement of the width of a 3D-printed orthopaedic implant according to any of the first, second, fourth, fifth, sixth or seventh aspect of the present invention, or of a solid osteoinductive filament according to the third aspect of the present invention.

[0312] Step 5 provides measurement of the width of a discrete hollow tunnel(s) of a 3D-printed orthopaedic implant according to any of the first, second, fourth, fifth, sixth, or seventh aspect of the present invention.Step 6 provides measurement of the width of a filament according to the third aspect of the present invention within a discrete hollow tunnel(s) of a 3D-printed orthopaedic implant according to any of the first, second, fourth, fifth, sixth, or seventh aspect of the present invention.

[0313] Angle & Direction of Discrete Hollow Tunnel(s): Micro-CT Imaging

[0314] 1. Scan the Implant : Place the implant in the micro-CT scanner and acquire high-resolution 3D imaging data, ensuring complete coverage of the internal structure.

[0315] 2. Reconstruct the 3D Model: Use reconstruction software to generate a voxel-based 3D model, allowing for detailed visualization of internal features, including tunnel(s).

[0316] 3. Segment T unnel(s): Apply density thresholding to differentiate low-density hollow tunnels, ensuring clear boundary identification.

[0317] 4. Determine T unnel Start and End Points: Identify the entry and end or exit points of each tunnel along the implant surface using 3D coordinate mapping (e.g., X, Y, Z positions).

[0318] 5. Calculate Tunnel Angle: Define a reference plane (e.g., the implant's base, an exterior surface of the implant (preferably the exterior surface of the implant with the entry or exit hole) or a predefined anatomical axis). Compute the tunnel’s orientation vector by determining the direction from the entry point to the end or exit point. Calculate the angle (0) relative to the reference plane using the dot product formula:

[0319]

[0320] where v is the tunnel vector and r is the reference direction (e.g., axial or transverse implant axis).

[0321] 6. Determine Direction: Express the tunnel's direction as a unit vector (e.g., along the X, Y, Z axes) or in polar coordinates if needed for surgical planning or implant alignment.

[0322] 7. Verify and Export Data: Cross-check measurements, refine segmentation if necessary, and export results for further analysis or comparison with design specifications.

[0323] Cross-Section of Discrete Hollow Tunnel(s) & Solid Osteoinductive Filament(s): Micro-CT Imaging

[0324] 1. Scan the Implant or Filament: Place the implant or filament in the micro- CT scanner and acquire high-resolution 3D imaging data, ensuring full coverage of the internal structure, including any hollow tunnel(s).

[0325] 2. Reconstruct the 3D Model: Use reconstruction software to generate a voxel-based 3D model, enabling detailed visualization of the implant’s internal features.

[0326] 3. Segment Hollow Tunnel(s) or Filament(s): For tunnels, apply density thresholding to distinguish solid material from hollow regions, ensuring clear identification of the tunnel boundaries. For filaments, apply density thresholding to differentiate the filament from any surrounding void spaces, ensuring clear boundary identification.

[0327] 4. Identify Cross-Sectional Planes: Select multiple cross-sectional slices perpendicular to the tunnel’s or filament’s central axis at defined intervals along its length. These can be chosen: at regular distances along the tunnel or filament for uniformity analysis; and / or at critical points, such as entry, midpoint, and optional exit point.5. Measure Cross-Sectional Dimensions: For each selected cross-section, fit a model to define the tunnel’s or filament’s shape, and compute cross- sectional area (A) using appropriate area calculation. Where the crosssection is elliptical or circular: fit an elliptical or circular model to define the tunnel’s or filament’s shape; measure major and minor diameters if the cross-section is elliptical and compute cross-sectional area (A) using:

[0328] major diameter minor diameter

[0329]

[0330] for elliptical tunnels or filaments, or

[0331]

[0332] for circular tunnels or filaments.

[0333] 6. Analyse Cross-Sectional Variability: Compare measurements at different points along the tunnel or filament to assess uniformity in shape and size.

[0334] 7. Verify and Export Data: Cross-check measurements, refine segmentation if necessary, and export results for further analysis or comparison with design specifications.

[0335] Quantiles of 3D-printed Orthopaedic Implant: Micro-CT Imaging

[0336] 1. Scan the Implant: Place the implant in the micro-CT scanner and acquire high-resolution 3D imaging data, ensuring complete coverage of the structure.

[0337] 2. Reconstruct the 3D Model: Process the scan data using reconstruction software to create a voxel-based 3D model, accurately representing the implant’s geometry.3. Define the Measurement Axis: Establish a reference axis (e.g., along the implant’s height, width, or depth) based on the desired quantile segmentation.

[0338] 4. Segment the Implant into Quantiles: Divide the implant into equal portions along the chosen axis, for example: quartiles (Q1, Q2, Q3, Q4) (25%, 50%, 75%, 100% divisions), or deciles (D1-D10) (10% increments) for finer segmentation. Percentiles can be used if higher resolution is required.

[0339] 5. Determine Quantile Boundaries: Calculate voxel-based thresholds for each quantile using:

[0340] Quantile Boundary = min + (max — min) x

[0341]

[0342]

[0343] where q is the quantile percentage, and min / max refer to the implant’s total height, width, or depth.

[0344] 6. Assign Quantile Labels to Each Region: Apply segmentation software to label each quantile region for visualization and statistical analysis.

[0345] 7. Verify and Export Data: Cross-check quantile divisions, refine segmentation if necessary, and export data for further geometric, mechanical, or biological analysis.

[0346] By the volume of the 3D-printed orthopaedic implant (according to the first, second, sixth, or seventh aspects, or of the kit of the fourth or fifth aspect of the present invention) as described herein is meant the total volume of the implant in question including: the porous osteoconductive scaffold (including any ‘negative’ space formed by its pores); the non-porous support portion (when present); any ‘negative’ space formed by the at least one discrete hollow tunnel, and optional central graft chamber as defined herein (when present); as well as any solid osteoinductive filament contained in a discrete hollow tunnel (when present), andany graft material of the optional central graft chamber (when present). By ‘negative’ space is meant any empty space formed by the pores of the porous osteoconductive scaffold, and any empty space formed by at least one discrete hollow tunnel, and optional central chamber, within the implant, when not filled with a solid osteoinductive filament and / or graft material. It will be appreciated that presence or absence of a solid osteoinductive filament in a discrete hollow tunnel of the implant, or graft material within the optional central graft chamber, will not substantially alter the calculation of the overall total volume of the implant as this total volume of the implant includes negative space within the implant and is calculated in the same way irrespective of whether the at least one discrete hollow tunnel and optionally the central graft chamber, are empty or filled.

[0347] Alternatively, the total volume of the implant may be calculated visually. This may be easily determinable by eye, or calculated using a measurement tool using known volume calculations such as height x width x depth, or other suitable volume calculations for the volume of irregular shapes. The volume of each of the non-porous support portion, porous osteoconductive scaffold, at least one discrete hollow tunnel and optional central graft chamber, may also be calculated in this way, using for example, the volume calculations height x width x depth for a tunnel of rectangular or square cross section, or r2h for a tunnel of circular or substantially circular cross section, where r is radius, and h is height.

[0348] For the 3D-printed orthopaedic implants according to the first or second aspect of the present invention, all features, e.g. shape, volume etc, may also be described in the CAD drawing using to program the 3D printer.

[0349] The volume of the 3D-printed orthopaedic implant of the sixth or seventh aspect of the present invention may be determined as described above. Micro-CT imaging may be carried out for the 3D-printed orthopaedic implant before (the first or second aspect of the present invention), and after insertion of the solid osteoinductive filament(s), and comparison made.

[0350] For the implant according to the sixth or seventh aspect of the present invention, the volume of a discrete hollow tunnel occupied by the filament(s) may bedetermined by comparing micro-CT imaging of the 3D-printed orthopaedic implant before (the first or second aspect of the present invention) and after insertion of the solid osteoinductive filament(s).

[0351] ‘Visually’ as used herein in reference to measurement methods includes preferably using a measuring instrument such as a ruler or tape.

[0352] Porosity

[0353] Bulk porosity of the 3D-printed orthopaedic implant according to any of the first, second, sixth or seventh aspects of the present invention, or of the kit according to the fifth or sixth aspect of the present invention can be determined using Archimedes’ Principle, which relies on the displacement of a liquid to measure the effective volume of a pore-containing structure. The process involves measuring the implant’s dry mass (Mdry) in air, followed by its immersed mass (M immersed) when fully submerged in a fluid of known density (e.g., ethanol). The difference between these two values corresponds to the displaced fluid volume, which represents the bulk volume (Vbuik) of the implant.

[0354] The bulk density (pbuik) of the implant is then calculated as:

[0355] Pbulk '

[0356]

[0357] The total porosity (%) is determined by comparing the bulk density to the theoretical density (ptheoreticai) of the solid material, using the following formula:

[0358] Porosity ( 100

[0359]

[0360] The porosity of the 3D-printed orthopaedic implant of the sixth or seventh aspect of the present invention may be determined as described above.Alternatively, micro-CT imaging may be carried out for the 3D-printed orthopaedic implant before (the first or second aspect of the present invention) and after insertion of the solid osteoinductive filament(s). The porosity of an implant may be determined using micro-CT Imaging, as follows:

[0361] 1. Scan the Implant: Place the implant in the micro-CT scanner and acquire high-resolution 3D imaging data using appropriate scan settings based on material density and pore size.

[0362] 2. Reconstruct the 3D Model: Use reconstruction software to convert the scan data into a voxel-based 3D model, ensuring accurate representation of the implant’s internal structure.

[0363] 3. Segment the Regions: Apply density thresholding to differentiate between solid material and void spaces (‘empty space’ - pores, empty tunnels, or optional empty central graft chamber) based on X-ray attenuation values.

[0364] 4. Analyse Porosity Metrics: Compute total porosity (%) by measuring the ratio of ‘empty space’ volume to total volume, and determine pore size distribution, interconnectivity, and surface area.

[0365] 5. Verify and Interpret Data: Cross-check results for accuracy, refine segmentation if necessary, and export data for further analysis or comparison with design specifications.

[0366] Alternatively, the porosity of the 3D-printed orthopaedic implant of the sixth or seventh aspect of the present invention may be determined by measurement of the volume of the filament(s) introduced therein, and this deducted from the total volume of the implant without any filaments introduced therein (the first or second aspect of the present invention). The ratio of these two volume values may then be used to calculate the porosity of the implant according to the sixth or seventh aspect of the present invention from the porosity of the implant according to thefirst or second aspect of the present invention, prior to introduction of a solid osteoinductive filament into a discrete hollow tunnel.

[0367] Pore Size

[0368] The pore size of the porous osteoconductive scaffold may be determined by Mercury Intrusion Porosimetry (MIP) to characterize the pore size distribution, total porosity, and interconnectivity of the porous structure within the 3D-printed orthopaedic implant. The application of controlled pressure to force mercury into the porous network, with the intrusion volume at varying pressures providing quantitative data on pore diameter and distribution. MIP enables the assessment of both macro- and microporosity, and is useful to describe structural uniformity and permeability characteristics.

[0369] To evaluate the surface area and microporosity of the porous osteoconductive scaffold and the 3D-printed orthopaedic implant, a method known as Brunauer-Emmett-Teller (BET) analysis may be employed, measuring gas adsorption at different relative pressures. This technique provides quantitative data on pore size distribution, particularly for sub-micron pores, by analysing the adsorption and desorption isotherms of gases such as nitrogen. BET analysis is useful for assessing the internal surface characteristics of the porous structure, which may influence material performance in specific applications.

[0370] EXAMPLES

[0371] Example 1

[0372] A solid osteoinductive filament according to the third aspect of the present invention was prepared as followed. A mixture of the following components was formed:

[0373] 75.34095 wt% PLGA (50:50);

[0374] 10 wt% poloxamer 407 (micronised);

[0375] 14.28405 wt% 2-hydroxypropyl-p-cyclodextrin;

[0376] 0.375 wt% rhBMP-2.The mixture was extended by hot melt extrusion under the following parameters: Feed rate: 2.2%

[0377] Screw speed: 20 rpm

[0378] Processing temperatures: 60 °C, 80 °C, 80 °C, 80 °C

[0379] Blade setting: 3.0 m / m & 50 mm

Claims

85CLAIMS1. A 3D-printed orthopaedic implant comprising a non-porous support portion and a porous osteoconductive scaffold, wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D- printed orthopaedic implant, and the 3D-printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width.

2. A 3D-printed orthopaedic implant comprising a porous osteoconductive scaffold and an optional non-porous support portion, wherein the 3D- printed orthopaedic implant has a porosity of at least 60%, and the 3D- printed orthopaedic implant comprises at least one discrete hollow tunnel extending into the porous osteoconductive scaffold, each discrete hollow tunnel being independently configured to allow insertion of a solid osteoinductive filament therein, and wherein each discrete hollow tunnel independently has: a volume of 7% or less of the volume of the 3D-printed orthopaedic implant; a substantially uniform cross-section; and a length that is at least three times greater than its width.

3. The 3D-printed orthopaedic implant according to claim 2, wherein the implant further comprises the non-porous support portion.

4. The 3D-printed orthopaedic implant according to claim 1 or 3, wherein the non-porous support portion forms 20% or less of the total external surface area of the 3D-printed orthopaedic, preferably 15% or less, more preferably 12% or less, such as 10% or less.

865. The 3D-printed orthopaedic implant according to any of claims 2 to 4, wherein the porous osteoconductive scaffold forms at least 60% of the volume of the 3D-printed orthopaedic implant.

6. The 3D-printed orthopaedic implant according to any of claims 1 to 5, wherein the porous osteoconductive scaffold forms at least 70% of the volume of the 3D-printed orthopaedic implant, preferably at least 75%, or at least 80%, such as 90% of the 3D-printed orthopaedic implant.

7. The 3D-printed orthopaedic implant according to claim 1 , or any of claims 3 to 6 where dependent thereon, wherein the 3D-printed orthopaedic implant has a porosity of at least 60%.

8. The 3D-printed orthopaedic implant according to any of claims 1 to 7, wherein the 3D-printed orthopaedic implant has a porosity of at least 70%, preferably at least 70%, more preferably at least 75%, or at least 80%, or at least 90% of the 3D-printed orthopaedic implant.

9. The 3D-printed orthopaedic implant according to any of claims 1 to 7, wherein the porous osteoconductive scaffold forms 80% or more of the total external surface area of the 3D-printed orthopaedic implant, preferably 85% or more, more preferably 88% or more, or 90% or more.

10. The 3D-printed orthopaedic implant according to any of claims 1 to 9, wherein the porous osteoconductive scaffold is present in every quartile of the 3D-printed orthopaedic implant, preferably every quintile, more preferably every octile, and more preferably every decile of the 3D-printed orthopaedic implant.

11. The 3D-printed orthopaedic implant according to any preceding claim, wherein the 3D-printed orthopaedic implant comprises two or more discrete hollow tunnels, preferably three or more discrete hollow tunnels, such as four or more discrete hollow tunnels.8712. The 3D-printed orthopaedic implant according to any preceding claim, wherein each discrete hollow tunnel independently has a volume of 5% or less of the 3D-printed orthopaedic implant.

13. The 3D-printed orthopaedic implant according to any preceding claim, wherein the at least one discrete hollow tunnel, has a width independently selected to be 5mm or less, preferably 4 mm or less, such as 3 mm or less, or 2 mm or less, and more preferably 1.5 mm or less.14 The 3D-printed orthopaedic implant according to any preceding claim, wherein the at least one discrete hollow tunnel has a width independently selected to be 0.15 mm or more, preferably 0.3 mm or more, and more preferably 0.5 mm or more.

15. The 3D-printed orthopaedic implant according to any preceding claim, wherein the at least one discrete hollow tunnel is independently selected to have a length of at least four times its width, preferably at least five times its width, such as at least six times its width.

16. The 3D-printed orthopaedic implant according to any preceding claim, wherein the at least one discrete hollow tunnel has a length independently selected to be at least 1 mm, preferably at least 4 mm, more preferably at least 8 mm, or at least 10 mm.

17. The 3D-printed orthopaedic implant according to any of claims 1 or 3 to 16, wherein the non-porous solid portion is formed of a non-resorbable material selected from: non-resorbable metals or alloys thereof, or combinations thereof; and non-resorbable polymers or combinations thereof; or combinations thereof, preferably, the non-porous solid portion is formed from a non-resorbable material selected from: titanium or an alloy thereof, and polyether ether ketone, or a combination thereof.

18. The 3D-printed orthopaedic implant according to any preceding claim, wherein the porous osteoconductive scaffold is formed of a material selected from: non-resorbable metals or alloys thereof, or combinations88thereof; and non-resorbable polymers or combinations thereof; resorbable polymers, or combinations thereof; and resorbable metals or combinations thereof; or combinations thereof, preferably wherein the porous osteoconductive scaffold is formed of a material selected from: titanium or alloys thereof, polyether ether ketone (PEEK), polylactic acid (PLA), polycaprolactone (PCL), polyglycolicacid (PGA), and polylactic-co-glycolic acid (PLGA), or combinations thereof, more preferably wherein the porous osteoconductive scaffold is formed from a material selected from: non- resorbable metals or alloys thereof, or combinations thereof; and non- resorbable polymers or combinations thereof; or combinations thereof, and more preferably wherein the porous osteoconductive scaffold is formed from a material selected from: titanium or an alloy thereof, and polyether ether ketone, or a combination thereof.

19. The 3D-printed orthopaedic implant according to any of claims 1, or 3 to 18, wherein the non-porous solid portion and the porous osteoconductive scaffold are formed of the same material.

20. The 3D-printed orthopaedic implant according to any preceding claim, wherein, in total, the discrete hollow tunnels have a volume of 40% or less of the volume of the 3D-printed orthopaedic implant, preferably 35% or less, or 30% or less, more preferably 25% or less, or 20% or less.

21. The 3D-printed orthopaedic implant according to any preceding claim, wherein the at least one discrete hollow tunnel is independently selected to be a blind-end tunnel or to extend completely through the 3D-printed orthopaedic implant.

22. The 3D-printed orthopaedic implant according to any preceding claim, wherein the 3D-printed orthopaedic implant is a bone implant and / or bone tissue scaffold, preferably a spinal implant such as a spinal fusion implant, and more preferably a spinal interbody fusion implant.8923. A solid osteoinductive filament operable to be inserted into a discrete hollow tunnel of a 3D-printed orthopaedic implant, wherein the solid osteoinductive filament has a length of at least three times its width and comprises an osteoinductive agent.

24. The solid osteoinductive filament according to claim 23, wherein the osteoinductive agent is selected from a bone morphogenic protein (BMP), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), sclerostin-binding molecules, and bisphosphonates, or combinations thereof, preferably a bone morphogenic protein, or combination thereof, more preferably a recombinant human bone morphogenic protein (rhBMP), and more preferably rhBMP-2.

25. The solid osteoinductive filament according to claim 23 or 24, wherein the osteoconductive agent is a bone morphogenic protein, preferably BMP-2, and the solid osteoinductive filament comprises 0.1 to 50 pg of osteoinductive agent per milligram of the solid osteoinductive filament, preferably 0.5 to 30 pg, or 1 to 20 pg, or 1.5 to 10 pg, or 2 to 5 pg of the osteoinductive agent per milligram of solid osteoinductive filament.

26. The solid osteoinductive filament according to any of claims 23 to 25, wherein the osteoinductive agent is present in the solid osteoinductive filament in an amount of 0.05 to 2 wt%, preferably 0.1 to 1 wt%, and more preferably 0.15 to 0.5 wt%.

27. The solid osteoinductive filament according to any of claims 23 to 26, wherein the solid osteoinductive filament has a length of at least four times its width, preferably at least five times its width.

28. The solid osteoinductive filament according to any of claims 23 to 27, wherein the solid osteoinductive filament is at least 1 mm in length, preferably at least 4 mm, such as at least 8 mm, and preferably at least 10mm in length.9029. The solid osteoinductive filament according to any of claims 23 to 28, wherein the solid osteoinductive filament has a width of 5 mm or less, preferably 4 mm or less, such as 3 mm or less, or 2 mm or less, and more preferably 1.5 mm or less.

30. The solid osteoinductive filament according to any of claims 23 to 29, wherein the solid osteoinductive filament has a width of from 0.15 mm or more, preferably 0.3 mm or more, and more preferably 0.5 mm or more.

31. The solid osteoinductive filament according to any of claims 23 to 30, wherein the solid osteoinductive filament is formed of a material comprising a polymer or a ceramic, or combination thereof, the material having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein.

32. The solid osteoinductive filament according to claim 31 , wherein the solid osteoinductive filament is formed of a material comprising a ceramic, the material having the osteoinductive agent attached thereto and / or tethered thereto.

33. The solid osteoinductive filament according to claim 31 , wherein the solid osteoinductive filament is formed of a material comprising a polymer, the material having the osteoinductive agent incorporated therein.

34. The solid osteoinductive filament according to claim 31 , wherein the solid osteoinductive filament is formed of a material comprising a polymer and ceramic, the material having the osteoinductive agent attached thereto and / or tethered thereto and / or incorporated therein.

35. The solid osteoinductive filament according to claim 31 , 32 or 34, wherein the ceramic is selected from calcium sulphate, calcium carbonate, calcium phosphate, a-tricalcium phosphate, p-tricalcium phosphate, and hydroxyapatite, or combinations thereof.9136. The solid osteoinductive filament according to claim 31 , 33 or 34, wherein the polymer is selected from the group comprising poly (lactide-co- glycolide)(PLGA), poly -lactic acid (PLA), polyethyleneimine (PEI), polylactic or polyglycolic acids, poly-lactide poly-glycolide copolymers, and poly-lactide, poly-glycolide, polyethylene glycol copolymers, polyethylene glycol (PEG), polyesters, poly (s-caprolactone), poly (3-hydroxy-butyrate), poly (s-caproic acid), poly (p-dioxanone), poly (propylene fumarate), poly (ortho esters), polyol / diketene acetals addition polymers, polyanhydrides, poly (sebacic anhydride) (PSA), poly (carboxybiscarboxyphenoxyphosphazene) (PCPP), poly [bis (p- carboxyphenoxy) methane] (PCPM), copolymers of SA, CPP and CPM, poly (amino acids), poly (pseudo amino acids), polyphosphazenes, derivatives of poly [(dichloro) phosphazene], poly [(organo) phosphazenes], polyphosphates, polyethylene glycol polypropylene block co-polymers, natural or synthetic polymers, silk, elastin, chitin, chitosan, fibrin, fibrinogen, polysaccharides, peptides, polypeptides±proteins, copolymers prepared from the monomers of any of these polymers, or blends, mixtures or combinations thereof, preferably wherein the polymer is selected from poly (lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), chitosan, or blends, mixtures or combinations thereof, and more preferably wherein the polymer is selected from a combination of poly (lactide-co-glycolide) and chitosan, or poly (lactide-co-glycolide) and polyethylene glycol.

37. The solid osteoinductive filament according to any of claims 31 and 33 to 36, wherein the material, and thus the solid osteoinductive filament, further comprises one or more additional component, preferably wherein the one or more additional component is selected from cyclodextrin, arginine or a salt thereof, trehalose, sucrose, dextran, polyethylene glycol (PEG), or combinations thereof, more preferably wherein the one or more additional component is selected is a cyclodextrin, for example 2-hydroxypropyl-p- cyclodextrin.9238. The solid osteoinductive filament according to any of claims 29 and 31 to 35, wherein the material, and thus the solid osteoinductive filament, further comprises a surfactant, preferably wherein the surfactant is selected from poloxamers, polysorbates, or combinations thereof, and more preferably a poloxamer.

39. A kit for providing a 3D-printed orthopaedic implant, the kit comprising:(i) a 3D-printed orthopaedic implant according to any of claims 1 to 22; and(ii) at least one solid osteoinductive filament according to any of claims 23 to 38.

40. The kit according to claim 39, wherein the kit comprises (ii) a plurality of solid osteoinductive filaments according to any of claims 23 to 28, preferably three or more, or four or more solid osteoinductive filaments.

41. The kit according to claim 39 or 40, wherein the solid osteoinductive filaments are the same or different.

42. The kit according to any of claims 39 to 41 , wherein the kit provides at least a number of solid osteoinductive filaments to fill the majority of the discrete hollow tunnels in the 3D-printed orthopaedic implant.

43. The kit according to any of claims 39 to 42, wherein the kit provides at least the same number of solid osteoinductive filaments as the number of discrete hollow tunnels in the 3D-printed orthopaedic implant.

44. A 3D-printed orthopaedic implant according to any of claims 1 to 22, wherein at least one discrete hollow tunnel contains a solid osteoinductive filament according to any of claims 23 to 38 therein, preferably a single solid osteoinductive filament.

45. The 3D-printed orthopaedic implant according to claim 44, wherein each discrete hollow tunnel of the 3D-printed orthopaedic implant contains a solid osteoinductive filament, preferably a single solid osteoinductive filament.

46. The 3D-printed orthopaedic implant according to claim 44 or 45, wherein the osteoinductive agent provides a total dose of the osteoinductive agent of 0.0002 to 12 mg to a subject in need, preferably 0.0005 to 10 mg, or 0.001 to 8 mg.

47. The 3D-printed orthopaedic implant according to claim 44 to 46, wherein the 3D-printed orthopaedic implant has a porosity of at least 55%, preferably at least 50%, or at least 45%, or at least 40%, such as 40%.

48. A method of promoting bone formation and / or bone fusion, preferably spinal bone formation and / or spinal bone fusion, using the 3D-printed orthopaedic implant according to any of claims 1 to 22 and at least one of the solid osteoinductive filaments according to any of claims 23 to 38, or the kit according to any of claims 39 to 43, the method comprising:(i) inserting a solid osteoinductive filament into at least one discrete hollow tunnel of the 3D-printed orthopaedic implant;(ii) implanting the 3D-printed orthopaedic implant into the body of a subject in need, preferably positioning the 3D-printed orthopaedic implant in a space between two bones or areas of bone, more preferably placing the 3D-printed orthopaedic implant into an intervertebral space between two spinal vertebrae.

49. A method of promoting bone formation and / or bone fusion, preferably spinal bone formation and / or spinal bone fusion, using the 3D-printed orthopaedic implant according to any of claims 44 to 47, the method comprising:(ii) implanting the 3D-printed orthopaedic implant into the body of a subject in need, preferably positioning the 3D-printed orthopaedic implant in a space between two bones or areas of bone, more preferably placing the 3D-printed orthopaedic implant into an intervertebral space between two spinal vertebrae.

50. The solid osteoinductive filament according to any of claims 23 to 38, for use as a medicament.

51. The solid osteoinductive filament according to any of claims 23 to 38, for use in the promotion of bone formation and / or bone fusion.

52. The kit according to any of claims 39 to 43, or the 3D-printed orthopaedic implant according to any of claims 44 to 47, for use as a medicament, when the porous osteoconductive scaffold is formed of a material selected from: resorbable polymers such as polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and polylactic-co-glycolic acid (PLGA) or combinations thereof; and resorbable metals such as magnesium alloys, or combinations thereof.

53. The kit according to any of claims 39 to 43, or the 3D-printed orthopaedic implant according to any of claims 44 to 47, for use in the promotion of bone formation and / or bone fusion, when the porous osteoconductive scaffold is formed of a material selected from: resorbable polymers such as polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and polylactic-co-glycolic acid (PLGA) or combinations thereof; and resorbable metals such as magnesium alloys, or combinations thereof.

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