Shape memory polymer for musculoskeletal repair

Abstract

An exemplary embodiment of the present disclosure provides a biomaterial, comprising a shape memory polymer material and a plurality of pores. The shape memory polymer material can be configured to deform from a first shape to a second shape upon application of a force and return to the first shape when the force is no longer applied. The plurality of pores can be disposed within the shape memory polymer material. The shape memory polymer material can define a first portion having a first porosity and a second portion having a second porosity different than the first porosity.

Description

SHAPE MEMORY POLYMER FOR MUSCULOSKELETAL REPAIRCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 574,805, filed on 4 April 2024, which is incorporated herein by reference in its entirety as if fully set forth below.FIELD OF THE DISCLOSURE

[0002] The various embodiments of the present disclosure relate generally to biomaterials, and more specifically, to novel shape memory biomaterials designed for the repair and regeneration of musculoskeletal tissues. These include articular cartilage, meniscus, bone, tendon, ligament, intervertebral discs, and any combination of the aforementioned hard and soft tissue interfaces.BACKGROUND

[0003] Musculoskeletal and orthopedic injuries impact millions of individuals annually, resulting in significant healthcare costs and economic burden. The conditions can impact articular cartilage, meniscus, bones, ligaments, tendons, and intervertebral discs leading to reduced mobility, untenable pain, and deteriorating quality of life. Articular cartilage, meniscus and ligament and tendons have significantly lower healing capacity compared to vascularized bone.

[0004] Clinical approaches to repair include palliative care and physical therapy, surgical interventions using autologous, allogeneic or xenogeneic grafts, or total joint replacement. Synthetic biomaterials, pharmacological agents, autologous and allogeneic cell-based approaches are also increasingly being utilized. The approaches carry limitations in delivery in minimally invasive surgeries, retention, and providing mechanical support throughout the duration of repair. Additional challenges include graft availability, suboptimal integration, donor site morbidity, and immune rejection. Current synthetic implants lack adequate multimodal mechanics to drive tissue regeneration. Therefore, several problems still exist with repairing musculoskeletal defects including but not limited to focal articular cartilage lesions, anterior cruciate ligament repairs and reconstructions, rotator cuff repairs and reconstructions, meniscus reconstruction and intervertebral disc reconstruction.

[0005] Cartilage is a specialized connective tissue found in various parts of the body, including joints, the rib cage, ear, nose, bronchial tubes, and intervertebral discs. It is characterized by itsresilience and ability to withstand compressive forces, making it essential for the smooth functioning of joints. However, cartilage has a limited capacity for self-repair due to its avascular nature, which restricts the supply of nutrients and the removal of waste products.

[0006] Cartilage damage can result from various causes, including trauma, degenerative diseases such as osteoarthritis, and congenital abnormalities. The inability of cartilage to regenerate effectively leads to pain, reduced mobility, and a significant decrease in the quality of life for affected individuals. Current treatment options for cartilage repair include chondroplasty, which includes the trimming of damaged tissue and smoothing surface marrow and stimulation / microfracture surgery (MSMF) (37% ~ 100,000-160,000), which involves the removal of damaged cartilage down to subchondral bone followed by micro-drilling to encourage tissue infiltration and cell-guided repair. Both procedures are done minimally invasively (MIS) through a keyhole incision limiting post-surgical inflammation, reducing operating times, length of stay and recovery times. Marrow stimulation in particular has seen an increase over the years amongst the > 40yr demographic accounting for 30-50% of all cartilage repairs in 2016. However, marrow stimulation has poor long term outcomes requiring revisions within 2-4 years of the initial surgery. Revision marrow stimulation procedures progressively regenerate inferior tissue. Other treatment methods include autologous chondrocyte implantation (ACI), osteochondral autograft transplantation, and the use of synthetic scaffolds. However, these methods have limitations such as donor site morbidity, limited availability of healthy cartilage, and suboptimal integration with the host tissue.

[0007] Anterior cruciate ligament (ACL) tears are among the most common injuries in athletes, with an incidence of approximately 1 in 3,500 individuals per year — amounting to 150,000 to 400,000 cases annually in the U.S. Current treatment strategies involve either primary repair with augmentation techniques aimed at preserving the native ligament or reconstruction using grafts.

[0008] Reconstruction typically utilizes autografts harvested from the hamstring, patellar tendon, or quadriceps tendon. While effective, autografts are associated with donor site morbidity and potential functional deficits. Alternatively, allografts are available, but they can pose challenges with biological integration and may result in slower healing.

[0009] Despite surgical advances, retear rates following ACL reconstruction remain high, with recurrence reported in up to 25% of cases — a rate that is significantly elevated among younger, active athletes.

[0010] Rotator cuff injuries are a common musculoskeletal condition, affecting approximately 6-24% of the U.S. population. These injuries may result from degenerative changes or acute trauma and are often initially asymptomatic or managed with palliative care. However, in younger patients, progressive disease and functional decline often necessitate surgical intervention.

[0011] Arthroscopic repair is the current standard of care for rotator cuff tears. Despite its minimally invasive nature and widespread adoption, retear rates remain high, particularly in larger tears and older patients. Retear incidence is also influenced by the type of repair technique used, with transosseous-equivalent (suture bridge) repairs exhibiting the highest recurrence rates — up to 30%. These failures are frequently attributed to inadequate tendon-to- bone integration and the inability to restore the native enthesis.

[0012] Patch augmentation has emerged as a promising adjunct, incorporating biomaterials, growth factors, and cell-based therapies to enhance biological healing. However, current approaches often suffer from limited biocompatibility, inconsistent surgical handling, and variable clinical outcomes.

[0013] There is a clear need for arthroscopically deliverable repair platforms that mimic native rotator cuff issue mechanics and promote enthesis regeneration. Specifically, materials engineered with compositional and mechanical gradients to facilitate hard-to-soft tissue transitions could significantly improve functional integration and long-term repair durability.

[0014] Spinal conditions such as degenerative disc disease or disc hernias are very common in the aging population. The gold standard treatments for damaged spinal discs are microdiscectomies or spinal fusions. For treatment of cervical spine pathologies, anterior cervical discectomy and fusion (ACDF) is performed combining both a discectomy and spinal fusion procedure. Approximately 132,000 ACDF procedures are performed in the US annually on patients with an average age of 60 years. However, microdiscectomies can cause mechanical instability in the spine leading to a high number of revision procedures performed on patients, while spinal fusions reduce patient mobility and increase back stiffness which can lead to increases in stress levels on adjacent spinal segments exacerbating the initial spine problems.

[0015] Recent advancements in tissue engineering and regenerative medicine have focused on developing biomaterials that can mimic the structure and function of natural musculoskeletal tissues. These biomaterials aim to provide a supportive environment for cell attachment, proliferation, and differentiation, ultimately leading to the formation of new cartilage tissue.Despite significant progress, there remains a need for novel biomaterials that offer improved biocompatibility, multi-scale and multi-modal mechanical properties, and the ability to promote musculoskeletal regeneration.

[0016] The present disclosure addresses these needs by providing novel biomaterials specifically designed for minimally invasive musculoskeletal tissue repair. These biomaterials are engineered to enhance cell viability, promote new tissue formation, and integrate seamlessly with the surrounding tissue, thereby offering a promising solution for the effective treatment of musculoskeletal defectsBRIEF SUMMARY

[0017] An exemplary embodiment of the present disclosure provides a biomaterial, comprising a shape memory polymer material and a plurality of pores. The shape memory polymer material can be configured to deform from a first shape under load free conditions to a second shape upon application of an external stimulus, which can be physical, chemical, thermal, photo- reactive (ie. UV, IR, NIR), electrical, magnetic, sonic, or any combination thereof, and return to the first shape when the force is no longer applied. The plurality of pores can be disposed within the shape memory polymer material. The shape memory polymer material can define a first portion having a first porosity and a second portion having a second porosity different than the first porosity.

[0018] In any of the embodiments disclosed herein, the shape memory polymer material can be a shape memory composite material. The shape memory composite material can comprise a first material and a second material. The first material can comprise a first polymer. The first and second materials can form a composition gradient in the polymer composite material.

[0019] In any of the embodiments disclosed herein, the first polymer can be selected from the group consisting of poly(glycerol-dodecanediateoate) (PGD); a free radical chain growth photocurable PGD; a free radical step growth photocurable PGD; a redox photocurable PGD; a [2+2] cycloaddition photocurable PGD; a derivative of PGD with a photoreactive macromer backbone; and combinations thereof.

[0020] In any of the embodiments disclosed herein, the second material can comprise one or more materials selected from the group consisting of: a second polymer; a ceramic; a metal; a matrix material; and combinations thereof.

[0021] In any of the embodiments disclosed herein, the second material can comprise the second polymer, and the second polymer can be selected from the group consisting of: polycaprolactone (PCL), polylactide (PLA), polyglycolide (PGA), poly(lactic-co-glycolicacid) (PLGA), polyurethane (PU), poly(glycerol sebacate) (PGS), poly(-diol citrates), poly(trimethylene carbonate) (PTMC), poly dioxanone (PDO), polyethylene glycol (PEG), polyhedral oligomeric silsesquioxane (POSS), natural oil copolyester urethanes, natural oils, natural polymers of hyaluronic acid, alginate, chitosan, silk, collagen, gelatin, dextran, cellulose, fibrin, elastin, and combinations thereof.

[0022] In any of the embodiments disclosed herein, the second material can comprise the second polymer, and the second material can be an electrically conductive biocompatible polymer.

[0023] In any of the embodiments disclosed herein, the electrically conductive biocompatible polymer can be selected from the group consisting of: polyanalines; polypyrroles; polythiophenes; carbon nanotubes; carbon nano fibers; and graphene.

[0024] In any of the embodiments disclosed herein, the second material can comprise the metal, and the metal can be selected from the group consisting of: magnesium, iron, copper, gold, silver, zinc, and combinations thereof.

[0025] In any of the embodiments disclosed herein, the second material can comprise the ceramic, and the ceramic can be selected from the group consisting of: hydroxyapatite; calcium phosphate; biphasic calcium phosphate; calcium phosphate cement; calcium sulfate; bioactive glass; silicate based calcium phosphate; magnesium based calcium phosphate; magnesium based bioactive glass; and combinations thereof.

[0026] In any of the embodiments disclosed herein, the second material can comprise the matrix material, and the matrix material can be selected from the group consisting of: minced cartilage; minced tendon; minced ligament; minced muscle; demineralized bone matrix; decellularized cartilage; decellularized tendon; decellularized ligament; small intestinal submucosa; placenta; decellularized micronized and vascular organs; adipose tissue; vascular stromal fragments from fat tissues; and combinations thereof.

[0027] In any of the embodiments disclosed herein, the biomaterial can further comprise a third material disposed in the polymer composite material, and the third material can be selected from the group consisting of: polysaccharides; proteins; peptides; nucleic acids; lipid modified proteins; lipid modified peptides; animal tissue; human tissue; human cell populations; medicinal compounds; antibiotics; and combinations thereof.

[0028] In any of the embodiments disclosed herein, the biomaterial can have a mechanical property gradient along at least a portion of the biomaterial.

[0029] In any of the embodiments disclosed herein, the mechanical property can be a bulk modulus gradient, a tensile modulus gradient, a shear modulus gradient, a viscoelasticity gradient, a mechanical creep gradient, an elasticity gradient, a permeability gradient, or a combination thereof.

[0030] In any of the embodiments disclosed herein, the biomaterial can have an electrical conductivity gradient along at least a portion of the biomaterial.

[0031] In any of the embodiments disclosed herein, the biomaterial can have a degradation gradient along at least a portion of the biomaterial wherein one aspect of the material can lose mass, volume, crosslink density or some combination thereof at a rate 1.0 IX or greater than a second aspect.

[0032] In any of the embodiments disclosed herein, the second shape can be a compressed shape and the first state is a decompressed shape.

[0033] In any of the embodiments disclosed herein, the biomaterial can comprise an aperture extending through the biomaterial and configured to receive and support a tissue.

[0034] In any of the embodiments disclosed herein, the aperture can have a cross-sectional area greater than cross-sectional areas of each of the plurality of pores.

[0035] Another embodiment of the present disclosure provides a biomaterial comprising a polymer shape memory material having a composition gradient of a first polymer material and a second material. The polymer shape memory material can comprise a plurality of pores.

[0036] These and other aspects of the present disclosure are described in the Detailed Description below and the accompanying drawings. Other aspects and features of embodiments will become apparent to those of ordinary skill in the art upon reviewing the following description of specific, exemplary embodiments in concert with the drawings. While features of the present disclosure may be discussed relative to certain embodiments and figures, all embodiments of the present disclosure can include one or more of the features discussed herein. Further, while one or more embodiments may be discussed as having certain advantageous features, one or more of such features may also be used with the various embodiments discussed herein. In similar fashion, while exemplary embodiments may be discussed below as device, system, or method embodiments, it is to be understood that such exemplary embodiments can be implemented in various devices, systems, and methods of the present disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The following detailed description of specific embodiments of the disclosure will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the disclosure, specific embodiments are shown in the drawings. It should be understood, however, that the disclosure is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings.

[0038] FIG. 1 illustrates a process of deploying a biomaterial in a cartilage defect of a subject, in accordance with some embodiments of the present disclosure.

[0039] FIG. 2 illustrates a process of deploying a biomaterial in a cartilage defect of a subject, in accordance with some embodiments of the present disclosure.

[0040] FIG. 3A depicts a conventional biomaterial.

[0041] FIG. 3B depicts a biomaterial, in accordance with some embodiments of the present disclosure.

[0042] FIGs. 4A-B depict biomaterials, in accordance with some embodiments of the present disclosure.

[0043] FIGs. 5A-D illustrate biomaterials employed on ligaments of a joint of a subject, in accordance with some embodiments of the present disclosure.

[0044] FIGs. 6A-B depict interconnected gradient porous constructs, in accordance with some embodiments of the present disclosure.

[0045] FIGs. 6C-D illustrate porous scaffolds deployed into a model of a cartilage and into the femoral condyle and tracheal groove, in accordance with some embodiments of the present disclosure.

[0046] FIG. 7 illustrates a process of deploying an expanded shape that can compress around and wrap tendons, ligaments for repair augmentation, in accordance with some embodiments of the present disclosure.

[0047] FIGs. 8A-D illustrate the location and shape of the vertebral body and the spine and the design and deployment of a gradient porous shape memory polymer as a replacement for a nucleus pulposa which has been delivered into a model scaffold of an annulus fibrosis, in accordance with some embodiments of the present disclosure.

[0048] FIGs. 9A-D is an illustration of a patient specific design and workflow for creating 3D printed porous gradient scaffolds matching anatomic specifications, in accordance with some embodiments of the present disclosure.DETAILED DESCRIPTION

[0049] Although preferred exemplary embodiments of the disclosure are explained in detail, it is to be understood that other exemplary embodiments are contemplated. Accordingly, it is not intended that the disclosure is limited in its scope to the details of construction and arrangement of components set forth in the following description or illustrated in the drawings. The disclosure is capable of other exemplary embodiments and of being practiced or carried out in various ways. Also, in describing the preferred exemplary embodiments, specific terminology will be resorted to for the sake of clarity.

[0050] To facilitate an understanding of the principles and features of the present disclosure, various illustrative embodiments are explained below. The components, steps, and materials described hereinafter as making up various elements of the embodiments disclosed herein are intended to be illustrative and not restrictive. Many suitable components, steps, and materials that would perform the same or similar functions as the components, steps, and materials described herein are intended to be embraced within the scope of the disclosure. Such other components, steps, and materials not described herein can include, but are not limited to, similar components or steps that are developed after development of the embodiments disclosed herein.

[0051] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0052] Also, in describing the preferred exemplary embodiments, terminology will be resorted to for the sake of clarity. It is intended that each term contemplates its broadest meaning as understood by those skilled in the art and includes all technical equivalents which operate in a similar manner to accomplish a similar purpose.

[0053] Ranges can be expressed herein as from “about” or “approximately” one particular value and / or to “about” or “approximately” another particular value. When such a range is expressed, another exemplary embodiment includes from the one particular value and / or to the other particular value.

[0054] By ‘ ‘comprising” or “containing” or “including” is meant that at least the named compound, member, particle, or method step is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, method steps, even if the other such compounds, material, particles, method steps have the same function as what is named.

[0055] Mention of one or more method steps does not preclude the presence of additional method steps or intervening method steps between those steps expressly identified. Similarly,it is also to be understood that the mention of one or more components in a device or system does not preclude the presence of additional components or intervening components between those components expressly identified.

[0056] The materials described as making up the various members of the invention are intended to be illustrative and not restrictive. Many suitable materials that would perform the same or a similar function as the materials described herein are intended to be embraced within the scope of the invention. Such other materials not described herein can include, but are not limited to, for example, materials that are developed after the time of the development of the invention.

[0057] Reference will now be made in detail to exemplary embodiments of the disclosed technology, examples of which are illustrated in the accompanying drawings and disclosed herein. Wherever convenient, the same references numbers will be used throughout the drawings to refer to the same or like parts.

[0058] Embodiments of the present disclosure aim to reduce pain, recovery time, and short and long-term complications following cartilage defect repair. To achieve these objectives, some embodiments utilize a 3D printable shape memory polymer (SMP) having elastomeric properties to manufacture devices for a range of cartilage tissue repair applications. Compared to current marrow stimulation augmentation, these devices can provide: 1) an elastomer with mechanical properties suitable for cartilage repair and exhibiting resistance to failure at higher strain rates compared to existing hydrogels or plastics; 2) off-the-shelf devices integrating with current minimally invasive surgical(MIS) practice; 3) self-fitting devices seamlessly interfacing with even irregular geometries and contours; 4) porous interconnected constructs supporting marrow sequestration and driving superior cartilage formation; 5) and biocompatible polymers comprised of bioavailable monomers with tunable degradation rates and mechanics through the repair timeframe.

[0059] Embodiments of the present disclosure can utilize novel shape memory polymers to address a range of orthopedic and musculoskeletal pathologies. Key differentiators amongst conventional technologies include: 1) the ability to deliver a solid construct using a minimally invasive approach; 2) a self-fitting device enabling seamless apposition to the defect walls; 3) tailored porosity at the sub-millimeter scale enabling instruction of tissue perfusion and growth; and 4) concomitant control of mechanics using various material formulations. Minimally invasive procedures are poised to replace open procedures with increasing adoption of robotic and Al assisted surgeries emphasizing the need for compatible surgical solutions.

[0060] Embodiments disclosed herein have many commercial applications. For example, some embodiments provide biomaterials that can be used to augment cartilage repair in the knee, elbow, hip, shoulder, foot, or ankle. Additionally, the biomaterial implant could be implemented as a single material or composite osteochondral plug. Porous biomaterial implants can also be fashioned as a biological reservoir for nucleus pulposa regeneration for intervertebral disc repair. Similarly, biomaterials of the present disclosure could also address meniscus repair. Mechanical tunability and controllable degradation rates combined with composite design and defined control of porosity at the microscale provide opportunities for various soft interface tissue repair applications including, but not limited to, marrow stimulation augmentation, osteochondral implantation, intervertebral disc repair, small joint repair, meniscus repair, and the like.

[0061] Embodiments of the present disclosure can be synthesized with and without photochemistry, can be made using additive manufacturing, subtractive manufacturing, molding, casting, porogen leaching, and gas foaming methods. The materials can be made to have uniform mechanical, electrical, and / or degradation properties, or a gradient of mechanical, electrical, and / or degradation properties, such as to emulate a target tissue.

[0062] Various biomaterials of the present disclosure can utilize shape memory polymer materials. These materials can be configured to deform from a first shape to a second shape upon application of a force and return to the first shape when the force is no longer applied. For example, FIG. 1 illustrates the deployment of a shape memory biomaterial of the present disclosure for repairing a cartilage defect. As shown in the left side of FIG. 1 , a shape memory polymer material in a compressed state can be inserted into a cartilage defect. Over time (as shown moving from left to right in FIG. 1), the shape memory polymer material can expand to an expanded / permanent state in the cartilage defect.

[0063] The shape memory polymer material of the present disclosure can be many shape memory polymer materials. In some embodiments, the shape memory polymer can comprise poly(glycerol-dodecanediateoate) (PGD). Many forms of PGD can be utilized in accordance with various embodiments of the present disclosure. The particular form of PGD can be selected based on an intended application of the biomaterial and corresponding desired properties for the biomaterial. Exemplary PGD materials, include, but are not limited to, a free radical chain growth photocurable PGD; a free radical step growth photocurable PGD; a redox photocurable PGD; a [2+2] cycloaddition photocurable PGD; a derivative of PGD with a photoreactive macromer backbone; and combinations thereof.

[0064] In some embodiments of the present disclosure, the shape memory polymer material can be a shape memory composite material. The shape memory composite material can comprise a first material and a second material. The first material can comprise a first polymer, which can be any of the PGD materials described above, and a second material.

[0065] As shown in FIG. 3A, some conventional biomaterials utilized composite materials including at least two materials 305 310. These conventional biomaterials, however, typically had clear delineations between the first 305 and second 310 materials, as shown by interface 315. This clear interface separating the first 305 and second 310 materials, substantially limits the functionality of these materials.

[0066] As shown in FIG. 3B, however, in some embodiments of the present disclosure, the first and second materials can form a composition gradient 330 in the polymer composite material between a first material 320 and a second material 325. As used herein, the term “composition gradient” refers to a variation in the relative concentrations of multiple materials over an area. For example, as shown in FIG. 3B, a top portion of the biomaterial is substantially comprises the first material 320. Progressing towards the bottom portion of the biomaterial, the relative concentration of the first material decreases and the relative concentration of the second material increases, until the biomaterial substantially comprises the second material at the bottom portion. Though only a single composition gradient 330 is shown in FIG. 3B, the present disclosure is not so limited. Rather, as those skilled in the art would appreciate, the biomaterials of the present disclosure can have many composition gradients along various portions of the biomaterial. Further, the composition gradients can be between more than just two materials, and include gradients involving three or more materials.

[0067] As discussed above, in some embodiments, the shape memory polymer material can be a composite material, including a first material (e.g., PGD material) and a second material. The second material can be selected based on a desired application and / or mechanical properties of the biomaterial. For example, in some embodiments, the second material can comprise one or more materials selected from the group consisting of: a second polymer; a ceramic; a metal; a matrix material; and combinations thereof.

[0068] In some embodiments, the second material can comprise the second polymer. Exemplary second polymers include, but are not limited to, polycaprolactone (PCL), polylactide (PLA), polyglycolide (PGA), poly(lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly(glycerol sebacate) (PGS), poly(-diol citrates), poly(trimethylene carbonate) (PTMC), poly dioxanone (PDO), polyethylene glycol (PEG), polyhedral oligomericsilsesquioxane (POSS), natural oil copolyester urethanes, natural oils, natural polymers of hyaluronic acid, alginate, chitosan, silk, collagen, gelatin, dextran, cellulose, fibrin, elastin, and combinations thereof.

[0069] In some embodiments, the second material can comprise the second polymer, and the second material can be an electrically conductive biocompatible polymer. In such embodiments, the second material can one or more of polyanalines, polypyrroles, polythiophenes, carbon nanotubes, carbon nano fibers, graphene, and combinations thereof.

[0070] In some embodiments, the second material can comprise a metal. Exemplary metals include, but are not limited to, magnesium, iron, copper, gold, silver, zinc, and combinations thereof.

[0071] In some embodiments, the second material can comprise a ceramic. Exemplary ceramics can include, but are not limited to, hydroxyapatite, calcium phosphate, biphasic calcium phosphate, calcium phosphate cement, calcium sulfate, bioactive glass, silicate based calcium phosphate, magnesium based calcium phosphate, magnesium based bioactive glass, and combinations thereof.

[0072] In some embodiments, the second material can comprise a matrix material Exemplary matrix materials can include, but are not limited to, minced cartilage, minced tendon, minced ligament, minced muscle, demineralized bone matrix, decellularized cartilage, decellularized tendon, decellularized ligament, small intestinal submucosa, placenta, decellularized micronized and vascular organs, adipose tissue, vascular stromal fragments from fat tissues, and combinations thereof.

[0073] In some embodiments, the shape memory polymer composite material can further comprise a third material. Exemplary third materials can include, but are not limited to, polysaccharides, proteins, peptides, nucleic acids, lipid modified proteins, lipid modified peptides, animal tissue, human tissue, human cell populations, medicinal compounds, antibiotics, and combinations thereof.

[0074] As shown in FIGs. 4A-B, in some embodiments, the biomaterial can comprise a plurality of pores 405, 410, 415 disposed along various portions of the biomaterial. In some embodiments, the pores 405, 410, 415 can be disposed in the biomaterial such that a first portion of the biomaterial can have a first porosity and a second portion of the biomaterial can have a second porosity different than the first porosity. As used herein, the term porosity refers to the presence of one or more holes in a continuous otherwise solid structure. Thechange in porosity along the biomaterial can be accomplished many ways, including by changing the relative sizes and / or spacing of the pores 405, 410, 415 throughout the biomaterial.

[0075] As shown in FIG. 4A, in some embodiments, the sizes of the pores can vary along different portions of the biomaterial. For example, the biomaterial can include a first portion 425 having small pores 405, a second portion 430 having medium sized pores 410, and a third portion 435 having large pores 415. Additionally, though not shown in FIG. 3 A, in some embodiments, the change in porosity throughout the biomaterial can be accomplished by altering relevant concentrations of small, medium, and / or large pores. For example, a first portion could include 25% small pores, 50% medium pores, and 25% large pores, and a second portion could include 100% large pores.

[0076] As shown in FIG. 4B, in some embodiments, the spacing between adjacent pores can vary in different portions of the biomaterial. For example, the biomaterial can include a first portion 440 and second portion 445 having equal sized pores 405 spaced closer together than pores 405 in a third portion 450.

[0077] As those skilled in the art would appreciate, the various compositions and porosities at different portions of the biomaterial can be selected to achieve many different mechanical properties along the biomaterial. Additionally, the compositions / porosity can be varied in different portions of the biomaterial to create various mechanical property gradients (i.e., continuous variation of a mechanical property) along the biomaterial. Exemplary mechanical properties can be varied along portions of the biomaterial to create these mechanical property gradients can include, but are not limited to, bulk modulus, tensile modulus, shear modulus, viscoelasticity, mechanical creep, elasticity, permeability (which can be useful to control tissue infiltration and cell growth), and combinations thereof.

[0078] Similarly, the various compositions and porosities at different portions of the biomaterial can be selected to achieve an electrical conductivity gradient along at least a portion of the biomaterial.

[0079] Similarly, the various compositions and porosities at different portions of the biomaterial can be selected to achieve a degradation gradient (i.e., when deployed in a subject, a rate of degradation continually varies) along at least a portion of the biomaterial.

[0080] The biomaterials of the present disclosure can be manufactured to be many different shapes depending on a desired application for the biomaterial. For example, as shown in FIGs. 4A-B, in some embodiments, the biomaterial can be cylindrically-shaped and can comprise anaperture 420 extending through the biomaterial. In some embodiments, as shown in FIGs. 4A- B, the aperture 420 can have a cross-sectional area greater than cross-sectional areas of each of the plurality of pores 405, 410, 415. The aperture 420 can allow the biomaterial to surround certain tissues, when desirable, as is shown in FIGs. 5A-B. As those skilled in the art would understand, however, the present disclosure is not limited to cylindrically-shaped materials; rather, many other shapes are contemplated as useful to repair any cartilage (or other) defect.

[0081] FIGs. 6A-B illustrate additional porous biomaterials of the present disclosure, and FIGs. 6C-D illustrate such biomaterials deployed in a tissue defect.

[0082] FIG. 7 further illustrates a process of deploying an expanded shape that can compress around and wrap tendons, ligaments for repair augmentation, in accordance with some embodiments of the present disclosure

[0083] Another example of a different shaped scaffold can be noted in FIGs. 8A-D (spine figure with nucleus pulposus scaffold) where the biomaterial of the present disclosure comprises a porous scaffold in the shape of a nucleus pulposus. This scaffold has been press- fit into a model scaffold of an annulus fibrosis to demonstrate the potential use of this device to replace native nucleus pulposus tissue. Additional embodiments of this device may act as a patch for the annulus fibrosus tissue surrounding the nucleus pulposus to prevent the herniation of nucleus pulposus tissue after incidental incisions are made into the annulus fibrosis to access the nucleus pulposus during therapeutic procedures like microdiscectomies or radiofrequency ablation. As those skilled in the art would understand, however, the present disclosure is not limited to materials shaped in the form of a nucleus pulposus; rather, many other shapes are contemplated as useful to repair any spine (or other) defect.

[0084] An example of implementing the manufacture of these porous gradient devices to meet patient specifications involves taking a 3D scan of patient anatomy (FIG. 9A), converting that to a 3D rendering (FIG. 9B)and implementing a finite a finite element analysis (FIG. 9C) with and without the implant design and assessing outcomes like contact pressures to sect designs. Finally the bench testing of the porous designs in 3D printed patient specific models (FIG. 9D) will provide customized feedback for fitting patient specific microporous devices.

[0085] It is to be understood that the embodiments and claims disclosed herein are not limited in their application to the details of construction and arrangement of the components set forth in the description and illustrated in the drawings. Rather, the description and the drawings provide examples of the embodiments envisioned. The embodiments and claims disclosed herein are further capable of other embodiments and of being practiced and carried out invarious ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purposes of description and should not be regarded as limiting the claims.

[0086] Accordingly, those skilled in the art will appreciate that the conception upon which the application and claims are based may be readily utilized as a basis for the design of other structures, methods, and systems for carrying out the several purposes of the embodiments and claims presented in this application. It is important, therefore, that the claims be regarded as including such equivalent constructions.

[0087] Furthermore, the purpose of the foregoing Abstract is to enable the United States Patent and Trademark Office and the public generally, and especially including the practitioners in the art who are not familiar with patent and legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The Abstract is neither intended to define the claims of the application, nor is it intended to be limiting to the scope of the claims in any way.

Claims

CLAIMSWhat is claimed is:

1. A biomaterial, comprising: a shape memory polymer material configured to deform from a first shape under load free conditions to a second shape upon application of an external stimulus and return to the first shape when the force is no longer applied; and a plurality of pores disposed within the shape memory polymer material, wherein the shape memory polymer material defines a first portion having a first porosity and a second portion having a second porosity different than the first porosity.

2. The biomaterial of claim 1, wherein the shape memory polymer material is a shape memory composite material, comprising: a first material, wherein the first material comprises a first polymer; and a second material, wherein the first and second materials form a composition gradient in the polymer composite material.

3. The biomaterial of claim 2, wherein the first polymer is selected from the group consisting of poly(glycerol-dodecanediateoate) (PGD); a free radical chain growth photocurable PGD; a free radical step growth photocurable PGD; a redox photocurable PGD; a [2+2] cycloaddition photocurable PGD; a derivative of PGD with a photoreactive macromer backbone; and combinations thereof.

4. The biomaterial of claim 2, wherein the second material comprises one or more materials selected from the group consisting of: a second polymer; a ceramic; a metal; a matrix material; and combinations thereof.

5. The biomaterial of claim 4, wherein the second material comprises the second polymer, the second polymer selected from the group consisting of: polycaprolactone (PCL), polylactide (PLA), polyglycolide (PGA), poly(lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly(glycerol sebacate) (PGS), poly(-diol citrates), poly(trimethylene carbonate) (PTMC), poly dioxanone (PDO), polyethylene glycol (PEG), polyhedral oligomeric silsesquioxane (POSS), natural oil copolyester urethanes, natural oils, natural polymers of hyaluronic acid, alginate, chitosan, silk, collagen, gelatin, dextran, cellulose, fibrin, elastin, and combinations thereof.

6. The biomaterial of claim 4, wherein the second material comprises the second polymer, wherein the second material is an electrically conductive biocompatible polymer.

7. The biomaterial of claim 6, wherein the electrically conductive biocompatible polymer is selected from the group consisting of: polyanalines; polypyrroles; polythiophenes; carbon nanotubes; carbon nano fibers; and graphene.

8. The biomaterial of claim 4, wherein the second material comprises the metal, the metal selected from the group consisting of: magnesium, iron, copper, gold, silver, zinc, and combinations thereof.

9. The biomaterial of claim 4, wherein the second material comprises the ceramic, the ceramic selected from the group consisting of: hydroxyapatite; calcium phosphate; biphasic calcium phosphate; calcium phosphate cement; calcium sulfate; bioactive glass; silicate based calcium phosphate; magnesium based calcium phosphate; magnesium based bioactive glass; and combinations thereof.

10. The biomaterial of claim 4, wherein the second material comprises the matrix material, the matrix material selected from the group consisting of: minced cartilage; minced tendon; minced ligament; minced muscle; demineralized bone matrix; decellularized cartilage; decellularized tendon; decellularized ligament; small intestinal submucosa; placenta; decellularized micronized and vascular organs; adipose tissue; vascular stromal fragments from fat tissues; and combinations thereof.

11. The biomaterial of claim 2, wherein the biomaterial further comprises a third material disposed in the polymer composite material, the third material selected from the group consisting of: polysaccharides; proteins; peptides; nucleic acids; lipid modified proteins; lipid modified peptides; animal tissue; human tissue; human cell populations; medicinal compounds; antibiotics; and combinations thereof.

12. The biomaterial of claim 1, wherein the biomaterial has a mechanical property gradient along at least a portion of the biomaterial.

13. The biomaterial of claim 12, wherein the mechanical property gradient is a bulk modulus gradient.

14. The biomaterial of claim 12, wherein the mechanical property gradient is a tensile modulus gradient.

15. The biomaterial of claim 12, wherein the mechanical property gradient is a shear modulus gradient.

16. The biomaterial of claim 12, wherein the mechanical property gradient is a viscoelasticity gradient.

17. The biomaterial of claim 12, wherein the mechanical property gradient is a mechanical creep gradient.

18. The biomaterial of claim 12, wherein the mechanical property gradient is an elasticity gradient.

19. The biomaterial of claim 12, wherein the mechanical property gradient is a permeability gradient.

20. The biomaterial of claim 1, wherein the biomaterial has an electrical conductivity gradient along at least a portion of the biomaterial.

21. The biomaterial of claim 1 , wherein the biomaterial has a degradation gradient along at least a portion of the biomaterial.

22. The biomaterial of claim 1, wherein the second shape is a compressed shape and the first state is a decompressed shape.

23. The biomaterial of claim 1, wherein the biomaterial comprises an aperture extending through the biomaterial and configured to receive and support a tissue.

24. The biomaterial of claim 20, wherein the aperture has a cross-sectional area greater than cross-sectional areas of each of the plurality of pores.

25. A biomaterial, comprising: a polymer shape memory material having a composition gradient of a first polymer material and a second material, the polymer shape memory material comprising a plurality of pores.

26. The biomaterial of claim 25, wherein the first polymer is selected from the group consisting of poly(glycerol-dodecanediateoate) (PGD); a free radical chain growth photocurable PGD; a free radical step growth photocurable PGD; a redox photocurable PGD; a [2+2] cycloaddition photocurable PGD; a derivative of PGD with a photoreactive macromer backbone; and combinations thereof.

27. The biomaterial of claim 25, wherein the second material comprises one or more materials selected from the group consisting of: a second polymer; a ceramic; a metal; a matrix material; and combinations thereof.

28. The biomaterial of claim 27, wherein the second material comprises the second polymer, the second polymer selected from the group consisting of: polycaprolactone (PCL), polylactide (PLA), polyglycolide (PGA), poly(lactic-co-glycolic acid) (PLGA), polyurethane(PU), poly(glycerol sebacate) (PGS), poly(-diol citrates), poly(trimethylene carbonate) (PTMC), poly dioxanone (PDO), polyethylene glycol (PEG), polyhedral oligomeric silsesquioxane (POSS), natural oil copolyester urethanes, natural oils, natural polymers of hyaluronic acid, alginate, chitosan, silk, collagen, gelatin, dextran, cellulose, fibrin, elastin, and combinations thereof.

29. The biomaterial of claim 27, wherein the second material comprises the second polymer, wherein the second material is an electrically conductive biocompatible polymer.

30. The biomaterial of claim 30, wherein the electrically conductive biocompatible polymer is selected from the group consisting of: polyanalines; polypyrroles; polythiophenes; carbon nanotubes; carbon nano fibers; and graphene.

31. The biomaterial of claim 27, wherein the second material comprises the metal, the metal selected from the group consisting of: magnesium, iron, copper, gold, silver, zinc, and combinations thereof.

32. The biomaterial of claim 27, wherein the second material comprises the ceramic, the ceramic selected from the group consisting of: hydroxyapatite; calcium phosphate; biphasic calcium phosphate; calcium phosphate cement; calcium sulfate; bioactive glass; silicate based calcium phosphate; magnesium based calcium phosphate; magnesium based bioactive glass; and combinations thereof.

33. The biomaterial of claim 27, wherein the second material comprises the matrix material, the matrix material selected from the group consisting of: minced cartilage; minced tendon; minced ligament; minced muscle; demineralized bone matrix; decellularized cartilage; decellularized tendon; decellularized ligament; small intestinal submucosa; placenta; decellularized micronized and vascular organs; adipose tissue; vascular stromal fragments from fat tissues; and combinations thereof.

34. The biomaterial of claim 25, wherein the biomaterial further comprises a third material disposed in the polymer composite material, the third material selected from the group consisting of: polysaccharides; proteins; peptides; nucleic acids; lipid modified proteins; lipid modified peptides; animal tissue; human tissue; human cell populations; medicinal compounds; antibiotics; and combinations thereof.

35. The biomaterial of claim 25, wherein the biomaterial defines a first portion having a first porosity and a second portion having a second porosity different than the first portion.

36. The biomaterial of claim 25, wherein the biomaterial has a mechanical property gradient along at least a portion of the biomaterial.

37. The biomaterial of claim 36, wherein the mechanical property gradient is a bulk modulus gradient.

38. The biomaterial of claim 36, wherein the mechanical property gradient is a tensile modulus gradient.

39. The biomaterial of claim 36, wherein the mechanical property gradient is a shear modulus gradient.

40. The biomaterial of claim 36, wherein the mechanical property gradient is a viscoelasticity gradient.

41. The biomaterial of claim 36, wherein the mechanical property gradient is a mechanical creep gradient.

42. The biomaterial of claim 36, wherein the mechanical property gradient is an elasticity gradient.

43. The biomaterial of claim 36, wherein the mechanical property gradient is a permeability gradient.

44. The biomaterial of claim 25, wherein the biomaterial has an electrical conductivity gradient along at least a portion of the biomaterial.

45. The biomaterial of claim 25, wherein the biomaterial has a degradation gradient along at least a portion of the biomaterial.

46. The biomaterial of claim 25, wherein the polymer shape memory material is configured to deform from a first shape to a second shape upon application of a force and return to the first shape when the force is no longer applied wherein the second shape is a compressed shape and the first state is a decompressed shape.

47. The biomaterial of claim 25, wherein the biomaterial comprises an aperture extending through the biomaterial and configured to receive and support a tissue.

48. The biomaterial of claim 47, wherein the aperture has a cross-sectional area greater than cross-sectional areas of each of the plurality of pores.

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