Engineered biotextile, fully biologic replacement joint including the same, and related methods for preparation and implantation thereof

Abstract

The present disclosure relates generally to cartilage repair and total joint arthroplasty and, more particularly, to engineered biotextiles, artificial implants comprising the engineered biotextiles, and fully biologic replacement joints comprising the same as well as related methods for preparing and implanting the engineered biotextiles and fully biologic replacement joints.

Description

PATENTENGINEERED BIOTEXTILE, FULLY BIOLOGIC REPLACEMENT JOINT INCLUDING THE SAME, AND RELATED METHODS FOR PREPARATIONAND IMPLANTATION THEREOFRELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 63 / 691 ,265 (filed September 5, 2024) and 63 / 703,469 (filed October 4, 2024), the entireties of which are hereby incorporated by reference for all purposes.TECHNICAL FIELD

[0002] The present disclosure relates generally to cartilage repair and total joint arthroplasty and, more particularly, to engineered biotextiles, artificial implants comprising the engineered biotextiles, and fully biologic replacement joints comprising the same as well as related methods for preparing and implanting the engineered biotextiles and fully biologic replacement joints.BACKGROUND

[0003] According to the CDC, an estimated 32.5 million individuals in the United States (U.S.) and 500 million individuals globally, suffer from the painfully debilitating condition of osteoarthritis (OA). OA is a leading cause of work disability in the U.S. and it adds a burden of $303B1 to the economy annually. Opioids, as a primary treatment of for 800,000 OA patients, result in criminal justice issues and cause lost work days cumulatively at a cost of $15k / person annually. The disease also aggravates diabetes and obesity by impairing or limiting mobility. Not only are these numbers rapidly increasing, but they are expected to further compound alongside population aging and increasing obesity trends. Despite its devastating impacts andscale, treatments for osteoarthritis lag musculoskeletal and chronic non- communicable diseases.

[0004] The majority of current treatments target pain relief as the primary outcome, but do not reverse the long-term course of cartilage degeneration; thus, most affected patients will become candidates for prosthetic joint replacement. In 2020, the estimated volume of total joint arthroplasty (TJA) procedures (hip and knee) was 1 .5M, which is projected to increase on average 11 % per year to -5.0M procedures by 2040. Currently, prosthetic implants have a short-to-medium term life cycle lasting approximately two decades, which introduces the burden of revision surgeries. Additionally, TJA patients’ mobility is limited to low-impact activities.SUMMARY

[0005] In view of the shortcomings of conventional solutions for repairing cartilage damage, the present disclosure advantageously provides an engineered biotextile (e.g., a knitted, multiphase osteochondral articular lining textile) capable of regenerating and / or replacing previously damaged or diseased cartilage (e.g., articular cartilage) to thereby prevent or mitigate any future joint pain. Also in view of the shortcomings of conventional prosthetic implants, the present disclosure advantageously provides a fully biologic replacement joint (e.g., comprising an engineered biotextile) and related methods for preparing and implanting the fully biologic replacement joint (e.g., total joint arthroplasty) that reverses osteoarthritis (OA) damage, provides lasting pain relief, and fully restores joint function.

[0006] As such, one aspect of the present disclosure can include a knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold. The fabric scaffold can comprise a plurality of biocompatible polymers having an alignment that supports the generation and growth of native cartilage.

[0007] Another aspect of the present disclosure can include a method for repairing, augmenting, or replacing damaged articular cartilage in a patient. The method can comprise affixing a knitted, multiphase osteochondral articular lining textile to a surgically relevant site in order to repair, augment, or replace the damaged articular cartilage. The knitted, multiphase osteochondral articular lining textile can comprise a fabric scaffold, which can include a plurality of biocompatible polymers having an alignment and orientation that mimics the alignment and orientation of collagen fibrils in native cartilage.

[0008] Another aspect of the present disclosure can include an artificial joint comprising a three-dimensional, osteoconductive bone backing and a knitted, multiphase osteochondral articular lining textile, which is coupled to the osteoconductive bone backing. The knitted, multiphase osteochondral articular lining textile can comprise a fabric scaffold, which can include a plurality of biocompatible polymers having an alignment and orientation that mimics the alignment and orientation of collagen fibrils in native cartilage.

[0009] Another aspect of the present disclosure can include a method for replacing a damaged joint in a patient comprising surgically implanting an artificial joint in place of the damaged joint. The artificial joint can comprise a three- dimensional, osteoconductive bone backing and a knitted, multiphase osteochondral articular lining textile, which is coupled to the osteoconductive bone backing. The knitted, multiphase osteochondral articular lining textile can comprise a fabric scaffold, which can include a plurality of biocompatible polymers having an alignment and orientation that mimics the alignment and orientation of collagen fibrils in native cartilage.

[0010] Another aspect of the present disclosure can include a fully biologic replacement joint. The fully biologic replacement joint can comprise: at least one load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; and one or more mesenchymal progenitor cells and / or differentiated primary cells physically associated with the at least one load-bearing structural component.

[0011] Another aspect of the present disclosure can include a method for preparing a fully biologic replacement joint. The method can comprise the steps of: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, loadbearing structural components into an acellular joint; seeding the acellular replacement joint with one or more mesenchymal progenitor cells and / or differentiated primary cells to form a cellularized joint; and conditioning the cellularized joint to form the fully biologic replacement joint.

[0012] Another aspect of the present disclosure can include a method for preparing an autologous, fully biologic replacement joint. The method can comprise the steps of: obtaining a three-dimensional image of a dysfunctional joint in a patient; preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more mesenchymal progenitor cells and / or differentiated primary cells previously obtained from the patient to form a cellularized joint; andconditioning the cellularized joint to form the autologous, fully biologic replacement joint.

[0013] Another aspect of the present disclosure can include a method for preparing an allogeneic, fully biologic replacement joint. The method can comprise the steps of: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more donor mesenchymal progenitor cells and / or differentiated primary cells obtained from a curated donor cell bank to form a cellularized joint; conditioning the cellularized joint to form the allogeneic, fully biologic replacement joint; and storing the allogeneic, fully biologic replacement joint under conditions sufficient to substantially preserve the biological, functional, and structural viability of the allogeneic, fully biologic replacement joint.

[0014] Another aspect of the present disclosure can include a fully biologic replacement joint prepared according to any of the methods disclosed herein.

[0015] Another aspect of the present disclosure can include a method for replacing a dysfunctional joint in a patient comprising surgically implanting a fully biologic replacement joint as disclosed herein.

[0016] Another aspect of the present disclosure can include an artificial implant comprising a three-dimensional, osteoconductive bone backing coupled to a knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold, the fabric scaffold comprising a plurality of biocompatible polymers having an alignment that supports the generation and growth of native cartilage, wherein the artificialimplant is sized and dimensioned to repair, augment or replace a damaged articular cartilage in a localized portion of an impacted joint.

[0017] Another aspect of the present disclosure can include a method for repairing, augmenting or replacing damaged articular cartilage in a patient. The method can comprise surgically implanting an artificial implant in place of the damaged articular cartilage. The artificial implant can comprise a three-dimensional, osteoconductive bone backing coupled to a knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold, the fabric scaffold comprising a plurality of biocompatible polymers having an alignment that supports the generation and growth of native cartilage, wherein the artificial implant is sized and dimensioned to repair, augment or replace a damaged articular cartilage in a localized portion of an impacted joint.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The foregoing and other features of the present disclosure will become apparent to those skilled in the art to which the present disclosure relates upon reading the following description with reference to the accompanying drawings, in which:

[0019] Figs. 1 A-D are schematic representations showing assembled (Figs. 1A-B) and exploded (Figs. 1 C-D) views of a knitted, multiphase osteochondral articular lining textile constructed in accordance with one aspect of the present disclosure;

[0020] Figs. 1 E-H are schematic representations showing assembled (Figs. 1 E-F) and exploded (Figs. 1 G-H) views of a knitted, multiphase osteochondral articular lining textile coupled to an osteoconductive bone backing in accordance with another aspect of the present disclosure;

[0021] Fig. 2 is a schematic illustration showing an alternative construction of the osteochondral articular lining textile in Figs. 1A-D;

[0022] Fig. 3 is a schematic illustration showing another alternative construction of the osteochondral articular lining textile in Figs. 1 A-D;

[0023] Fig. 4 is a schematic illustration showing one example of an osteochondral articular lining textile constructed in accordance with the present disclosure; and

[0024] Fig. 5 is a schematic illustration showing a simplified synovial joint comprising a first bone having a joint head with articular cartilage disposed thereon, a second bone having a joint socket with an osteochondral articular lining textile of the present application disposed thereon, a joint capsule, and a joint cavity filled with synovial fluid;

[0025] Fig. 6 is a process flow diagram illustrating a method for preparing a fully biologic replacement joint according to one aspect of the present disclosure;

[0026] Fig. 7 is a process flow diagram illustrating a method for preparing an autologous, fully biologic replacement joint according to another aspect of the present disclosure;

[0027] Fig. 8 is a process flow diagram illustrating a method for preparing an allogeneic, fully biologic replacement joint according to yet another aspect of the present disclosure;

[0028] Fig. 9 is a schematic illustration showing one example of the method in Fig. 7;

[0029] Fig. 10 is a schematic illustration showing one example of the method in Fig. 8

[0030] Fig. 11 is an image showing collagen monofilaments having a flat cross section (left panel) with decreasing width (middle and right panels) upon spinning;

[0031] Figs. 12A-B are a series of graphs showing fiber width (Fig. 12A) and load failure (Fig. 12B) vs filament / yarn width;

[0032] Fig. 13 is an image showing that spun monofilaments provided better knit structure than flat monofilaments;

[0033] Fig. 14 is a series of images showing that 0.3 mm thread knitted better than the wider thread;

[0034] Fig. 15 is a series of images showing successful knitting osteochondral articular lining textiles using collagen and PCL and that knit density can be adjust by needle tension (Right panel: Loose; Left panel: Tight);

[0035] Fig. 16 is a series of images showing different knitting iterations;

[0036] Fig. 17 is a series of images showing osteochondral articular lining textiles knitted using PLGA yarns in the spacer and bone interface with PCL and / or collagen in the articular face to increase the mechanical properties;

[0037] Fig. 18 is a graph showing that PLGA improves the compressive strength of the osteochondral articular lining textiles;

[0038] Fig. 19 is a schematic showing three different types of knitting patterns that were explored;

[0039] Figs. 20A-D are a series of graphs showing aggregate modulus (Fig. 20A), Young’s modulus (Fig. 20B), longitudinal shear modulus (Fig. 20C), and transverse shear modulus (Fig. 20D) of the osteochondral articular lining textiles;

[0040] Fig. 21 is a series stereomicroscope images of different osteochondral articular lining textiles;

[0041] Fig. 22 is a graph showing average pore sizes for the different osteochondral articular lining textiles;

[0042] Fig. 23 is a table showing percent porosity for the different osteochondral articular lining textiles;

[0043] Fig. 24 is a graph showing stress (MPa) for different osteochondral articular lining textiles;

[0044] Fig. 25 is a graph showing tensile modulus (MPa) for different osteochondral articular lining textiles;

[0045] Fig. 26 is a table showing the tensile modulus (MPa) and stress (MPa) for the different osteochondral articular lining textiles; and

[0046] Figs. 27A-B are a series of graphs showing change in Young’s modulus before and after fatigue testing (Fig. 27A) and shear modulus degradation for the different osteochondral articular lining textiles.DETAILED DESCRIPTION

[0047] Definitions

[0048] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the present disclosure pertains.

[0049] Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. In particular, in methods stated as comprising one or more steps or operations it is specifically contemplated that each step comprises what is listed (unless that step includes a limiting term such as “consisting of”), meaning that each step is not intended to exclude, for example, other additives, components, integers or steps that are not listed in the step.

[0050] In the context of the present disclosure, the term “about”, when expressed as from “about” one particular value and / or “about” another particular value, also specifically contemplated and disclosed is the range from the one particular value and / or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. Finally, it should be understood that all of the individual values and subranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these aspects are explicitly disclosed.

[0051] Optionally, in some aspects, when values or characteristics are approximated by use of the antecedents “about,” “substantially,” or “generally,” it is contemplated that values within up to 15%, up to 10%, up to 5%, or up to 1 % (above or below) of the particularly stated value or characteristic can be included within the scope of those aspects.

[0052] As used herein, phrases such as “between X and Y” and “between about X and Y” can be interpreted to include X and Y.

[0053] As used herein, phrases such as “between about X and Y” can mean “between about X and about Y”.

[0054] As used herein, phrases such as “from about X to Y” can mean “from about X to about Y”.

[0055] It will be understood that when an element is referred to as being “on”, “attached” to, “connected” to, “coupled” with, “contacting”, etc., another element, it can be directly on, attached to, connected to, coupled with or contacting the other element or intervening elements may also be present. In contrast, when an element is referred to as being, for example, “directly on”, “directly attached” to, “directly connected” to, “directly coupled” with or “directly contacting” another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

[0056] Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature’s relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms can encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features.

[0057] As used herein, the terms “first,” “second,” etc. should not limit the elements being described by these terms. These terms are only used to distinguish one element from another. Thus, a “first” element discussed below could also be termed a “second” element without departing from the teachings of the present disclosure. The sequence of operations (or acts / steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.

[0058] As used herein, the terms “optionally” and “optional” can mean that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

[0059] As used herein, the term “autologous” can refer to biological tissue (e.g., cells) from the same subject, e.g., where the donor and recipient are the same subject.

[0060] As used herein, the term “allogeneic” can refer to biological tissue (e.g., cells) of the same species that differ genetically to the biological tissue in comparison, e.g., where the donor and the recipient are not the same subject.

[0061] As used herein, the term “joint” can refer to a bodily structure connecting two or more adjacent parts of the skeleton, e.g., a region where two bones meet or make contact. A joint may be classified histologically or functionally. Histological classification is based on the predominant connective tissue type composing the joint, either fibrous, cartilaginous, or synovial. Functional classification is based on the amount of movement the joint permits. The three functional joint types include the immovable synarthrosis, slightly moveable amphiarthrosis, and freely moveable diarthrosis. The two joint classification schemes correlate: synarthroses are fibrous; amphiarthroses are cartilaginous; and diarthroses are synovial.

[0062] As used herein, the term “fully biologic replacement joint” can refer to a type of total joint replacement that does not include the use of synthetic (e.g., metal and / or plastic) replacement prosthetic components.

[0063] As used herein, the term “stem cell” can refer to an undifferentiated cell that can be induced to proliferate. A stem cell is capable of self-maintenance,meaning that with each cell division, one daughter cell will also be a stem cell. Stem cells can be obtained from embryonic, post-natal, juvenile, or adult tissue. In one example, stem cells can be genetically-induced from adult cells.

[0064] As used herein, the term “progenitor cell” can refers to an undifferentiated cell derived from a stem cell, and is not itself a stem cell. Some progenitor cells can produce progeny that are capable of differentiating into more than one cell type.

[0065] As used herein, the term “mesenchymal progenitor cell” can refer to a cell having the potential to differentiate into discrete mesenchymal tissues, such as bone, cartilage, adipose tissue, and muscle. For example, a mesenchymal progenitor cells can be capable of differentiation into at least two committed cell types selected from the group including, but not limited to, adipose, areolar, osseous, cartilaginous, elastic and fibrous connective. One example of a mesenchymal progenitor cells is a mesenchymal stem cell (MSC).

[0066] As used herein, the term “mesenchymal stem cell” or “MSC” can refer to cells that are derived from the embryonal mesoderm and can be isolated from many sources, including adult bone marrow, peripheral blood, fat, placenta, and umbilical blood, among others. MSCs can differentiate into many mesodermal tissues, including muscle, bone, cartilage, fat, and tendon. There is considerable literature on these cells. See, for example, U.S. Patent Nos. 5,486,389; 5,827,735; 5,811 ,094; 5,736,396; 5,837,539; 5,837,670; and 5,827,740. See, also, Pittenger, M. etal, Science, 284:143-147 (1999). In some instances, MSCs can be derived from an apparently healthy subject (e.g., a human subject); that is, a subject who has no signs and / or symptoms of a disease. The term can also be used interchangeably with “multipotent stromal cell”.

[0067] As used herein, the term “differentiated primary cell” can refer to any primary cell that is not, in its native form, pluripotent as that term is defined herein.

[0068] As used herein, the term “pluripotent” can refer to a cell with the capacity, under different conditions, to differentiate to more than one differentiated cell type, and preferably to differentiate to cell types characteristic of all three germ cell layers. Pluripotent cells are characterized primarily by the ability to differentiate to more than one cell type, preferably to all three germ layers, using, for example, a nude mouse teratoma formation assay. Pluripotency can also be evidenced by the expression of embryonic stem cell markers, although the preferred test for pluripotency is the demonstration of the capacity to differentiate into cells of each of the three germ layers.

[0069] As used herein, the terms “subject” and “patient” can be used interchangeably and refer to a vertebrate, such as a mammal (e.g., a human). Mammals can include, but are not limited to, humans, dogs, cats, horses, cows, and pigs.

[0070] As used herein, the terms “mimetic” or “biomimetic”, when used in connection with the osteochondral articular lining textile of the present disclosure, can refer to an osteochondral articular lining textile that is biologically inert ( / .e., will not cause an immune response / rejection) and is designed to resemble a structure (e.g., articular cartilage) that occurs naturally in a mammalian (e.g., human) body and that promotes osteochondral tissue growth and function when implanted into the body.

[0071] As used herein, the term “biodegradable” can refer to materials which are enzymatically or chemically degraded in vivo into simpler chemical species. In one example, referring to an osteochondral articular lining textile of the presentdisclosure, the term can mean that the osteochondral articular lining textile, once implanted into a mammalian body, will begin to degrade. The rate of biodegradation may be engineered into the osteochondral articular lining textile based on, e.g., the polymer(s) used, the ratio of copolymers used, the degree (if any) of crosslinking, and other parameters known to those of skill in the art.

[0072] As used herein, the term “non-biodegradable polymer” can refer to a polymer that is chemically inert and does not decompose ( / .e., resistant to environmental or physiological degradation). Exemplary non-biodegradable polymers can include, but are not limited to, polystyrene, polyesters, non- biodegradable polyurethanes, polyureas, polyethylene vinyl acetate), polypropylene, polymethacrylate, polyethylene, polycarbonates, and polyethylene oxide).

[0073] As used herein, the term “bioactive agent” can refer to any chemical, biological, or pharmaceutically acceptable agent or molecule that does not deleteriously affect the structure or function of the osteochondral articular lining textile of the present disclosure and which may provide an added therapeutic benefit to a patient.

[0074] As used herein, the term “aligned polymers” can refer to one or more groups of polymers which are oriented along the same or substantially the same directional axis. Examples of aligned polymers can include, but are not limited to, groups of parallel polymers.

[0075] As used herein, the term “synthetic polymer” can refer to a polymer that is not naturally occurring and that is produced via chemical synthesis.

[0076] As used herein, the term “natural polymer” can refer to a polymer that is found in nature and that may be derived from natural sources or produced synthetically.

[0077] As used herein, the term “biocompatible” can refer to a synthetic or natural material used to replace part of a living system or to function in intimate contact with living tissue. Biocompatible materials can interface with biological systems to evaluate, treat, augment, or replace any tissue or function of the body. A biocompatible material can have the ability to perform with an appropriate host response in a specific application and does not have toxic or injurious effects on biological systems.

[0078] As used herein, the term “anisotropic” can refer to greater load-bearing capacity in a dominant direction due to polymer (e.g., collagen fibril) alignment.

[0079] As used herein, the term “osteochondral tissue” can refer to a biological tissue that comprises, consists essentially of, or further consists of articular cartilage and a subchondral bone region.

[0080] As used herein, the term “biotextile” can refer to any one or combination of materials used to create a textile, including but not limited to a fabric, film, etc., that is generated from a raw material that is comprised of biodegradable and biocompatible polymers and optional other constituents, such as cells, cross-linking agents, biocompatible ceramic materials, bioactive agents, and the like.

[0081] As used herein, the term “woven” can refer to the method or process of interlacing two materials (e.g., threads or yarns) so that they cross each other to produce a woven fabric.

[0082] As used herein, the term “knitted”, when referring to an engineered biotextile (e.g., an osteochondral articular lining textile) of the present disclosure, can mean any biotextile that is manufactured by a knitting process including, but not limited to, double layer knitting e.g., weft knitting using a two-bed weft-knitting machine), warp knitting, or 3-D printing.

[0083] As used herein, the term “seeding” can refer to a process or step whereby cells are brought into contact with a support matrix (e.g., a fabric scaffold of the present disclosure), and adhere (with or without an adhesive) to the support matrix for a period of time. Seeded cells may divide and / or differentiate on the support matrix. In some instances, cells are seeded onto a support matrix prior to being implanted into a subject.

[0084] As used herein, the term “defect” can refer to an abnormality or imperfection, for example, in tissue in a joint of a subject. In some embodiments, a defect is a cartilage defect (e.g., damaged cartilage, less cartilage than desired, or cartilage that is less intact and coherent than desired). In some embodiments, a cartilage defect is a defect in tissue in an articular joint, for example, a knee joint. In some embodiments, a cartilage defect is a chondral defect. In another embodiment, a defect is an osteochondral defect (e.g., involving both cartilage and bone). In one example, a defect is a focal or localized defect. A focal defect can include a single, contiguous area of chondral or osteochondral damage which may be repaired, augmented, or replaced by osteochondral articular lining textile (according to the present disclosure) or an osteochondral articular lining textile coupled to a bone backing (according to the present disclosure). In some instances, a focal defect can affect less than or about 33% of the total surface area of a damaged joint area.Similarly, “localized repair” can refer to the repair, augmentation, or replacement of a focal defect that is less substantial than a partial joint replacement. In another example, a defect is a partial defect. A partial defect can include a partial joint defect as compared to a joint replacement (arthroplasty), which entails repair and / or replacement of a larger joint area. As such, a partial joint defect can include repair,replacement, or augmentation of a single joint condyle or just a patella, but not the entirety of all surfaces in the joint.

[0085] Overview

[0086] Currently, the longevity of conventional joint implants is 15-20 years, which is well below the life expectancy of most patients, thus requiring multiple implant surgeries over a lifetime. For example, conventional total knee arthroplasty (TKA) commonly removes the menisci and intrasynovial ligaments, regardless of whether they are inflicted by osteoarthritis (OA); consequently, TKA only partly recovers articulation. Furthermore, tissue engineering approaches to date have focused on cartilage, ligament, meniscus, and bone components separately. Moreover, there are no currently available products capable of fully remodeling into tissues that can reconstitute the joint.

[0087] Advantageously, the fully biologic replacement joints and associated methods of the present disclosure provide a living biological implant capable of restoring all tissue components of a degenerated joint; allowing a more comprehensive and effective strategy for treating OA. Designed modularly and flexibly, the fully biologic replacement joints of the present disclosure address the worst-case scenario of regenerating an entire diseased or dysfunctional joint while also providing the provision to replace components that are inflicted by OA.

[0088] To this end, the fully biologic replacement joints and associated methods of the present disclosure comprise numerous innovative aspects including, but not limited to:(1) feedback-controlled bioreactors to drive expedited expansion and effective differentiation of cells (e.g., chondrocytes, mesenchymal progenitor cells);(2) online process monitoring to confirm endpoint quality of engineered jointtissue components (e.g., load-bearing structural components);(3) computationally-guided 3D printing of osteoconductive scaffolds or networks with biodegradable anchoring posts for surgical fixation of a fully biologic replacement joint, and for physiological load-sharing during the remodeling phase;(4) recapitulation of the meniscal tissue anisotropy;(5) a knitted, double-layered osteochondral articular lining textile;(6) establishment of a donor-blood derived engineered cartilage, ligament and meniscus bank;(7) in silico design, development, and individualization of fully biologic replacement joints (and components thereof) for targeted safety and efficacy measures; and(8) digital twinning to capture implanted joint’s pre- and post-surgical trajectory to provide recommendations on weight-bearing and rehabilitation.

[0089] Fully Biologic Replacement Joint

[0090] One aspect of the present disclosure can include a fully biologic replacement joint 2 (Figs. 9-10). A fully biologic replacement joint 2 of the present disclosure can be constructed as a replacement for any joint (complete or partial) of a subject in need thereof (e.g., a diseased or dysfunctional joint). In one example, a fully biologic replacement joint 2 constructed in accordance with the present disclosure can include a complete or partial knee joint, a complete or partial shoulder joint, a complete or partial hip joint, a complete or partial joint comprising a hand e.g., a complete or partial finger joint), a complete or partial elbow joint, a complete or partial joint comprising a foot (e.g., a complete or partial toe joint), a complete orpartial neck joint, a complete or partial joint comprising an ankle, a complete or partial temporomandibular joint, a complete or partial temporomandibular joint, a complete or partial intervertebral disc, or a complete or partial joint comprising a wrist joint (e.g., a complete or partial radiocarpal joint). In another example, a fully biologic replacement joint 2 constructed in accordance with the present disclosure can include a total knee joint. Where replacement or repair of a partial joint is indicated, for example, it will be appreciated that one or more osteochondral plugs (e.g., as described below and illustrated in Figs. 1 E-H) can be prepared according to the present disclosure and implanted to repair or replace the partial joint.

[0091] The fully biologic replacement joint 2 can comprise at least one loadbearing structural component selected from the group consisting of ligaments, menisci, articular cartilage (e.g., an osteochondral articular lining textile 10), an osteoconductive scaffold or bone backing 28, and combinations thereof. The loadbearing structural components can be biomimetic (with respect to a particular native joint being replaced); that is, the load-bearing structural components of the present disclosure can have a structure and function that mimic(s) the structural components of a healthy joint.

[0092] Osteoconductive scaffold

[0093] In one example, a load-bearing structural component of a fully biologic replacement joint 2 (e.g., a knee) can comprise an osteoconductive scaffold or bone backing 28. The bone backing 28 can be formed using patient images generated by CT, which can form the basis for 3D printing (3DP) of the trabecular network and the surrounding cortical pore, each at a porosity to allow perfusion and vascular ingrowth to support the viability of seeded cells (discussed below). In one example, the bone backing 28 can comprise poly(c-caprolactone) (PCL) and hydroxyapatite (HA)particles, which can be 3D printed at an optimal formulation (e.g., based on preferred mechanical, osteoconductive and degradation properties thereof), such as PCL molecular weight, HA particle size, pore size and porosity. Other examples of osteoconductive materials that can be used to form the bone backing 28 include, but are not limited to, -TCP, brushite, bioglass, biocoral, calcium, and citrate.

[0094] In some instances, an osteoconductive scaffold (e.g., bone backing 28) can be adapted to fixedly receive one or more fully resorbable, osteogenic anchoring posts 4. In one example, osteogenic anchoring posts 4 can be made of a bioresorbable metal alloy, such as a magnesium alloy (see, e.g., Dean etal., “Biocompatibility of a novel heat-treated and ceramic-coated magnesium alloy (Mg- 1 .2Zn-0.5Ca-0.5Mn) for resorbable skeletal fixation devices”, MRS Communications 10(3) :1 -8 (Aug 2020). Such posts 4 can be press-fit into holes that are drilled in the underlying host bone to provide stable attachment of the bone backing 28. Posts 4 can be used, for example, at distal femoral, internal patellar, and superior tibial plateau surfaces. One end of each post 4 can be integrated with the porous bone backing 28 with sufficient strength to accept ambulatory load while bone forms in vivo. Unlike the current standard-of-care for total knee arthroplasty, which includes large, relatively flat metal trays that replace much of the host bone of the condylar surface, a fully biologic replacement joint 2 (e.g., knee) of the present disclosure can securely mate with the patient’s condylar surface, with a focus on integration with the host bone. The material(s) comprising the bone backing 28 (e.g., PCL and HA) can be fabricated with various tolerances to provide a robust press-fit of the osteogenic anchoring posts 4. The osteogenic anchoring posts 4 can additionally or optionally include flutes on them to increase the surface area and thus the pull-out forcesbetween the two components. Additionally, the posts 4 can include periodic holes therein to accommodate bone ingrowth for additional stabilization post-implantation.

[0095] Articular cartilage

[0096] In another example, a load-bearing structural component of a fully biologic replacement joint 2 (e.g., a knee) can comprise an engineered biotextile that mimics articular cartilage. In one example, such as an engineered biotextile can comprise an osteochondral articular lining textile (OCALT). As discussed in further detail below, the osteochondral articular lining textile is a multiphasic (e.g., biphasic, triphasic, etc.) biotextile whose construction permits repair and regeneration of osteochondral tissue, including both articular cartilage, subchondral bone and underlying bone as well. In particular, the osteochondral articular lining textile of the present application comprises a plurality of biocompatible polymers having an alignment and orientation that mimics the alignment and orientation of collagen in native cartilage and can thereby be used to regenerate and / or replace previously damaged or diseased tissue (e.g., osteochondral tissue) in a subject to mitigate or prevent future joint pain in the subject.

[0097] The advantages of the osteochondral articular lining textile of the present application flow, at least in part, from the fact that it is a knitted - and not woven - biotextile. Knitting permits the use of distinct materials (e.g., yarns) comprising different constituents (e.g., polymers having desired directionality) to construct the separate constituent phases or layers of the osteochondral articular lining textile ( / .e., top face or articular layer, bottom face or osteoconductive layer, and the support components that interconnect the two layers, thereby constituting the thickness of the osteochondral articular lining textile). The presence of separate phases or layers advantageously permits construction of a separate bone-inducing face (or layer) anda separate cartilage-inducing phase (or layer) by utilizing bone-inducing fibers in the bottom face (or layer) and nowhere else. Further, the presence of separate phases or layers advantageously provides phases (or layers) that precisely mimic cartilage directionality. Woven textiles, however, cannot achieve such targeted and precise function because of their cross-hatched, interweaved fiber construction, which not only results in undesirable bone generation throughout the entire woven textile, but also result in filaments having an orientation and alignment that does not mimic cartilage directionality ( / .e., vertical filaments to the articular face along the thickness of the cartilage).

[0098] Figs. 1 A-D illustrate a knitted, multiphase osteochondral articular lining textile 10 constructed in accordance with one aspect of the present disclosure. The osteochondral articular lining textile 10 can comprise a fabric scaffold 12 (e.g., a nonwoven fabric scaffold). The fabric scaffold 12 can comprise a plurality of the same or different biocompatible polymers. In one example, the entirety of the fabric scaffold 12 can comprise the same type of biocompatible polymer. All or only a portion of the biocompatible polymers comprising the scaffold 12 can be biodegradable and / or non-biodegradable. In one example, the biocompatible polymers comprising the fabric scaffold 12 can include synthetic polymers, natural polymers, and combinations thereof.

[0099] Non-limiting examples of biodegradable and biocompatible polymers can include aliphatic polyesters, poly(amino acids), modified proteins, polydepsipeptides, copoly(ether-esters), polyurethanes, polyalkylenes oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, poly(e- caprolactone)s, polyanhydrides, polyarylates, polyphosphazenes, polyhydroxyalkanoates, polysaccharides, modified polysaccharides, polycarbonates,polytyrosinecarbonates, polyorthocarbonates, poly(trimethylene carbonate), poly(phosphoester)s, polyglycolide, polylactides, polyhydroxybutyrates, polyhydroxyvalerates, polydioxanones, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(maleic anhydride), polyvinylalcohol, polyesteramides, polycyanoacrylates, polyfumarates, polyethylene glycol), polyoxaesters containing amine groups, poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(dioxanone)s, poly(alkylene alkylate)s, biopolymers, collagen, silk, chitosan, alginate, derivatives thereof, and a blend of two or more of the preceding polymers.

[0100] In one example, the fabric scaffold 12 can be entirely or partially comprised of a natural polymer, such as collagen. In such instances, the collagen may be any type of collagen, including collagen types I to XXVIII, alone or in any combination. It will be appreciated that the collagen can also include exogenously added non-collagenous proteins (e.g., fibronectin, fibrinogen, keratin, or silk proteins), glycoproteins, proteoglycans, polysaccharides, glycosaminoglycans (e.g., chondroitins and heparins), or the like.

[0101] In certain aspects, the biocompatible polymers can be formulated as an anisotropic structure selected from the group consisting of a microfiber, a nanofiber, a fiber, a thread, a yarn, a multifilament, or a combination thereof.

[0102] In one example, a fabric scaffold 12 of the present disclosure can be comprised of anisotropic collagen fiber bundles arranged as a thread (e.g., a single strand of collagen) or rope (e.g., a twisted or braided strand of one or more collagen fibers). In some instances, one or all of the collagen threads comprising the fabric scaffold 12 can have a non-circular or non-rounded cross-section. In otherinstances, to improve knittability of the collagen threads, one or all of the collagen threads can be spun and / or plied so as to obtain a cross-section that is flat and wide.

[0103] Advantageously, the polymers comprising the fabric scaffold 12 have an alignment and orientation that mimics the alignment and orientation of collagen fibrils in native cartilage. As discussed in more detail below, the polymers of the fabric scaffold 12 are oriented and aligned in such a way to mimic the natural architecture of a soft tissue (e.g., articular cartilage) to be repaired. Moreover, the polymers and the subsequently formed fabric scaffold 12 are controlled with respect to their physical properties, such as for example, fiber diameter, knitting density ( / .e., number of filaments per unit area), pore diameter, and porosity so that the mechanical properties of the fabric scaffold are similar to the native tissue to be repaired, augmented or replaced. By designing the fabric scaffold 12 of the present application so that the biocompatible polymers have an alignment and orientation that mimics the alignment and orientation of collagen fibrils in native cartilage, improved fixation and function is achieved by minimizing stress concentrations and mediating load transfer between bones (comprising a joint).

[0104] In another aspect, the fabric scaffold 12 can have a thickness Ts(Fig. 1 B) of about 1 mm to about 5 mm, or about 1 mm to about 4 mm, or about 1 mm to about 3 mm, or about 1 mm to about 2 mm, or about 2 mm to about 5 mm, or about 2 mm to about 4 mm, or about 2 mm to about 3 mm, or about 3 mm to about 5 mm, or about 4 mm to about 5 mm. In one example, the fabric scaffold 12 can have a thickness Ts of about 3 mm to about 5 mm (e.g., 3 mm to 5 mm).

[0105] In another aspect, the fabric scaffold 12 can have an elastic modulus of about 0.2 MPa to about 10 MPa. In one example, the fabric scaffold 12 can have an elastic modulus of about 0.2 MPa to about 9.5 MPa, about 0.2 MPa to about 9 MPa,about 0.2 MPa to about 8.5 MPa, about 0.2 MPa to about 8 MPa, about 0.2 MPa to about 7.5 MPa, about 0.2 MPa to about 7 MPa, about 0.2 MPa to about 6.5 MPa, about 0.2 MPa to about 6 MPa, about 0.2 MPa to about 5.5 MPa, about 0.2 MPa to about 5 MPa, about 0.2 MPa to about 4.5 MPa, about 0.2 MPa to about 4 MPa, about 0.2 MPa to about 3.5 MPa, about 0.2 MPa to about 3 MPa, about 0.2 MPa to about 2.5 MPa, about 0.2 MPa to about 2 MPa, about 0.2 MPa to about 1 .5 MPa, or about 0.2 MPa to about 1 MPa. In another example, the fabric scaffold 12 can have an elastic modulus of about 2 MPa to about 5 MPa (e.g., 2 MPa to 5 MPa).

[0106] Although the fabric scaffold 12 is illustrated as having a rectangular configuration, it will be appreciated that the fabric scaffold can have any other regular or irregular configuration (e.g., square, circular, ovoid, etc.) as deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient. Similarly, it will be appreciated that the fabric scaffold 12 can be of any size and dimensions deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient.

[0107] Referring again to Figs. 1 A-D, the fabric scaffold 12 can comprise an articular layer 14 having a major surface 16 adapted to physically interface with a corresponding articular layer (Fig. 5) of a joint surface. The fabric scaffold 12 (Figs.1 A-D) can further comprise an osteoconductive layer 18 that is continuous with the articular layer 14 and has a major surface 20 adapted to anchor the osteochondral articular lining textile 10 to a bone surface (illustrated in Fig. 5). Additionally, the fabric scaffold 12 can include one or more interconnecting support components 22 that extend between the major surface 16 of the articular layer 14 and the major surface 20 of the osteoconductive layer 22. The one or more interconnectingsupport components 22 can comprise a plurality of biocompatible polymers having an alignment and orientation that is different than the alignment and orientation of the biocompatible polymers comprising at least the articular layer 14.

[0108] The articular layer 14 can be continuous with the osteoconductive layer 18 such that the fabric scaffold 12 has a vertically layered or multi-ply (e.g., 2-ply) configuration. For example, the fabric scaffold 12 can be configured such that a second major surface 24 of the articular layer 14 is in direct contact with the major surface 20 of the osteoconductive layer 18; in other words, the articular and osteoconductive layers can be arranged in parallel. Such an arrangement is distinguishable from a serial arrangement; whereby, the articular and osteoconductive layers 14 and 18 are arranged in an end-to-end manner.

[0109] As shown in Figs. 1C-D, the articular layer 14 can have a thickness Ta defined by the major surface 16 and the second major surface 24. The thickness Taof the articular layer 14 can be any non-zero value that is less than the total thickness Tsof the fabric scaffold 12. Although the articular layer 14 is illustrated as having a rectangular configuration, it will be appreciated that the articular layer can have any other regular or irregular configuration (e.g., square, circular, ovoid, etc.) as deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient. Similarly, it will be appreciated that the articular layer 14 can be of any size and dimensions deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient. In some instances, the articular layer 14 can be sized and dimensioned in an identical, substantially identical, or different manner as the osteoconductive layer 18.

[0110] In one aspect, all or substantially all of the biocompatible polymers comprising the articular layer 14 can have a parallel (or substantially parallel) orientation - relative to a longitudinal axis LA of the fabric scaffold 12 - that mimics the native orientation of collagen fibrils in articular cartilage, thereby providing the fabric scaffold with the ability to provide mechanical resistance to shear forces applied thereto during joint movement.

[0111] In another aspect, all or only a portion of the biocompatible polymers comprising the articular layer 14 can be biodegradable and / or non-biodegradable.

[0112] In one example, the articular layer 14 can be comprised of collagen (e.g., 2-ply collagen) and be prepared via electrochemical compaction as described, for example, by Cheng etal. (Biomaterials 2008, 29(22):3278-3288).

[0113] Referring to Fig. 1 D, the osteoconductive layer 18 has a thickness To defined by the major surface 20 and a second major surface 26. The thickness Toof the osteoconductive layer 18 can be any non-zero value that is less than the total thickness Tsof the fabric scaffold 12. Although the osteoconductive layer 18 is illustrated as having a rectangular configuration, it will be appreciated that the osteoconductive layer can have any other regular or irregular configuration (e.g., square, circular, ovoid, etc.) as deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient. Similarly, it will be appreciated that the osteoconductive layer 18 can be of any size and dimensions deemed appropriate (e.g., by a medical professional) for repair, augmentation, or replacement of damaged articular cartilage in a patient. In some instances, the osteoconductive layer 18 can be sized and dimensioned in an identical, substantially identical, or different manner as the articular layer 14.

[0114] In one aspect, all or substantially all of the biocompatible polymers comprising the osteoconductive layer 18 can have a different alignment and orientation as compared to the alignment and orientation of the biocompatible polymers comprising the articular layer 14. For example, all or substantially all of the biocompatible polymers comprising the osteoconductive layer 18 can have an alignment and orientation that is non-parallel with the alignment and orientation of the biocompatible polymers comprising the articular layer 14. In another example, all or substantially all of the biocompatible polymers comprising the osteoconductive layer 18 can have an alignment and orientation that is orthogonal (90°) to (or substantially orthogonal, e.g., oblique or neither parallel nor at a right angle to a specified or implied line, such greater than 45° but less than 90°) top the alignment and orientation of the biocompatible polymers comprising the articular layer 14.Moreover, the orientation and alignment of polymers comprising the osteoconductive layer 18 is such that the osteoconductive layer mimics the native orientation of collagen fibrils in the deep zone of articular cartilage and thereby provides the fabric scaffold 12 with the ability to provide mechanical resistance to compressive forces applied thereto during joint movement.

[0115] In another aspect, all or only a portion of the biocompatible polymers comprising the osteoconductive layer 18 can be biodegradable and / or non- biodegradable.

[0116] In one example, the osteoconductive layer 18 can be comprised of poly(e- caprolactone) (PCL) monofilament.

[0117] In another aspect, the osteoconductive layer 18 can further comprise a biocompatible ceramic at any convenient concentration based on the method of incorporation used and the desired physical properties of the fabric scaffold 12, suchas promoting osteoconductivity. By way of example, collagen fibers containing about 1%, about 5%, about 15%, or about 25% hydroxyapatite (HA) can be prepared and formulated as the osteoconductive layer 18. Advantageously, at least partially coating collagen fibers of the osteoconductive layer 18 with HA provides the ability to control / stimulate bone growth on one side of the osteochondral articular lining textile 10 and anchor the osteochondral articular lining textile to a respective bone surface (e.g., a tibia or femur).

[0118] As discussed above, the osteochondral articular lining textile 10 has a knitted construction by virtue of one or more interconnecting support components 22 that extend(s) between the major surface 16 of the articular layer 14 and the major surface 20 of the osteoconductive layer 18, thereby connecting or joining the articular layer with the osteoconductive layer and anchoring the osteochondral articular lining textile 10 into the subchondral layer (when implanted).Advantageously, the one or more interconnecting support components 22 provide(s) the osteochondral articular lining textile 10 with compressive stiffness and templates directionality of cartilage growth in the load-bearing axis.

[0119] The one or more interconnecting support components 22 can extend throughout the articular layer 14 as shown, for example, in Figs. 1 A-D and Fig. 4, and be knitted into a portion of the osteoconductive layer 18 so as to anchor the osteochondral articular lining textile 10 into the subchondral layer (when implanted). The degree (e.g., depth) into which the one or more interconnecting support components 22 can be knitted into the osteoconductive layer 18 can vary as shown, for example, in Figs. 1 A-D and Fig. 2.

[0120] The one or more interconnecting support components 22 can be comprised of one or a combination of biocompatible polymers, such as thosediscussed above, having an alignment and orientation that is different than the alignment and orientation of the polymers comprising at least the articular layer 14. For example, all or substantially all of the biocompatible polymers comprising the one or more interconnecting support components 22 can have an alignment and orientation that is non-parallel with the alignment and orientation of the biocompatible polymers comprising at least the articular layer 14. In another example, all or substantially all of the biocompatible polymers comprising the one or more interconnecting support components 22 can have an alignment and orientation that is orthogonal to (or substantially orthogonal to) the alignment and orientation of the biocompatible polymers comprising at least the articular layer 14.

[0121] In some instances, all or substantially all of the biocompatible polymers comprising the one or more interconnecting support components 22 can have an alignment and orientation that is substantially the same as, the same as, substantially different from, or different from the alignment and orientation of the biocompatible polymers comprising the osteoconductive layer 18.

[0122] In another aspect, all or only a portion of the biocompatible polymers comprising the one or more interconnecting support components 22 can be biodegradable and / or non-biodegradable.

[0123] In one example, all or only a portion of the one or more interconnecting support components 22 can comprise multi-ply or multifilament collagen (e.g., 2-ply collagen, 3-ply collagen, etc.). Alternatively, all or only a portion of the one or more interconnecting support components 22 can comprise single-ply or monofilament collagen.

[0124] In another example, all or only a portion of the one or more interconnecting support components 22 can comprise multifilament collagen (e.g., 2-ply collagen) ormonofilament collagen and PCL. Alternatively, collagen and PCL monofilaments can be co-plied as hybrid multifilament and used to construct the entirety of the fabric scaffold 12 or only a component thereof, such as only the articular layer 14 or only the osteoconductive layer 18.

[0125] In another example, the articular layer 14, the osteoconductive layer 18, and the one or more interconnecting support components 22 can be made of the same biocompatible polymer.

[0126] The one or more interconnecting support components 22 can have a variety of shapes and dimensions. As shown in Fig 4, for example, each of the interconnecting support components 22 can have a cylindrical or pillar-shaped configuration. The one or more interconnecting support components 22 can be knitted into the fabric scaffold 12 in a variety of patterns depending, for example, upon the biomechanical properties desired for the osteochondral articular lining textile 10. As shown in Figs. 1A-D and Fig. 2, for example, the one or more interconnecting support components 22 can be knitted into the fabric scaffold 12 in a serpentine pattern. Alternatively, as shown in Fig. 3, the one or more interconnecting support components 22 can be knitted into the fabric scaffold 12 as a series of spaced-apart blocks or columns.

[0127] Advantageously, the stiffness of the osteochondral articular lining textile 10 can be controlled independently by adjusting certain characteristics of the fabric scaffold 12, such as, the number of threads per unit area, the orientation of the threads with respect to the vertical, the diameter / denier of the threads and / or the material the threads are made of. In one embodiment, for example, the number of threads per unit area can be adjusted by using a tighter knit density and / or by using multiple ply yarns. In another embodiment, the porosity of the articular andosteoconductive layers 14 and 18 can be controlled independently by using different knitting patterns on these opposing faces. In one example, all or only a portion of the osteochondral articular lining textile 10 (e.g., only the articular layer 14, only the osteoconductive layer 18, or both) can have a porosity from about 20 percent by volume to about 90 percent by volume, e.g., about 20 percent by volume to about 80 percent by volume, about 20 percent by volume to about 70 percent by volume, about 20 percent by volume to about 60 percent by volume, about 20 percent by volume to about 50 percent by volume, about 20 percent by volume to about 40 percent by volume, about 20 percent by volume to about 30 percent by volume, about 30 percent by volume to about 90 percent by volume, about 40 percent by volume to about 90 percent by volume, about 50 percent by volume to about 90 percent by volume, about 60 percent by volume to about 90 percent by volume, about 70 percent by volume to about 90 percent by volume, or about 80 percent by volume to about 90 percent by volume.

[0128] In another aspect, all or only a portion of the fabric scaffold 12 can be made weft knitting or warp knitting. For example, only the articular layer 14, only the osteoconductive layer 18, or both, can be made weft knitting or warp knitting. Where weft knitting is used, any one or combination of knitting patterns can be used: jacquard; interlock; pique; tuck stitch; miss stitch (float); cable; pointelie; plated structure; mesh; waffle; and honeycomb. Where warp knitting is used, any one or combination of knitting patterns can be used: raschel jacquard; tricot stitch; atlas stitch; pillar stitch; cord stitch; double bar jacquard; mesh structure; open or closed loop structures; multiaxial warp knitting patterns; and tubular warp knit structures. Advantageously, various knit patterns can be selected to provide the fabric scaffold 12 with suitable fiber directionalities, porosities, surface textures, and the like.

[0129] In another aspect, the fabric scaffold 12 can be cross-linked or uncrosslinked. In some instances, all or only a portion of the fabric scaffold 12 can be cross-linked with a cross-linking agent before, after, or during assembly of the fabric scaffold. Only the articular layer 14, only the osteoconductive layer 18, or both the articular layer and the osteoconductive layer can be cross-linked. Non-limiting examples of cross-linking agents can include carbodiimides, aldehydes, lysl-oxidase, N-hydroxysuccinimide esters, imidoesters, hydrazides, and maleimides, as well as various natural crosslinking agents, including genipin.

[0130] In one example, the articular layer 14 can be comprised of collagen threads that are covalently cross-linked with genipin to strengthen the threads (see, e.g., Uquillas, J.A. et al., J Meeh Behav Biomed Mater. 2012, 15:176-189, and Manickam, B. et al., Curr Drug Deliv. 2014, 11 (1 ):139-145).

[0131] In another aspect, all or only a portion of the fabric scaffold 12 can be seeded or populated with mammalian cells, such as, e.g., human cells, in order to promote tissue repair and regeneration. A population of cells can be physically associated with (e.g., in direct contact with) all or only a portion of the fabric scaffold 12. In some instances, only the articular layer 14 of the fabric scaffold 12 is seeded or populated with cells (e.g., stem cells) to facilitate generation of a bone-cartilage interface. In such instances, the articular layer 14 can be free of any agent(s) (e.g., HA) that promote(s) osteogenic differentiation of the cells.

[0132] Non-limiting representative examples of suitable cells that may be incorporated into or onto the fabric scaffold 12 can include mesenchymal progenitor cells, differentiated primary cells, mesenchymal stem cells, fibroblasts, chondrocytes, osteoblasts, osteoblast-like cells, stem cells, progenitor cells, and combinations thereof. In some instances, the cells are from a compatible donor subject (i.e.,allogeneic cells). In other instances, the cells are from the patient (i.e., autologous cells).

[0133] In another aspect, one or more bioactive agents can be incorporated into or distributed throughout all or only a portion of the fabric scaffold 12 (e.g., only the articular layer 14 or only the osteoconductive layer 18). Non-limiting examples of bioactive agents can include anti-infectives, extracellular matrix components, antibiotics, bisphosphonates, hormones, analgesics, anti-inflammatory agents, growth factors (e.g., TGF-P3), angiogenic factors, chemotherapeutic agents, antirejection agents, RGD peptides, and combinations thereof. Bioactive agents can be incorporated into the fabric scaffold 12 using procedures well known in the art, including, e.g., immersion, impregnation, vacuum suction, spraying, and the like.

[0134] Another aspect of the present disclosure, illustrated in Figs. 1 E-H, can include an artificial implant 11 comprising a three-dimensional, osteoconductive bone backing 28 coupled or attached to (e.g., directly attached) to an osteochondral articular lining textile 10, wherein the artificial implant is sized and dimensioned to repair, augment or replace a damaged articular cartilage in a localized portion (e.g., a focal defect) of an impacted joint (e.g., a joint having cartilage damage as a result of trauma, disease, natural wear, etc.). As shown in Figs. 1 E-H, the osteoconductive bone backing 28 can be coupled or attached (e.g., directly attached) to the osteoconductive layer 18 of the fabric scaffold 12. In particular, all or only a portion of the second major surface 26 of the osteoconductive layer 18 can be coupled or attached (e.g., directly attached) to a first major surface 30 of the osteoconductive bone backing 28. Coupling or attachment of the osteoconductive bone backing 28 to the osteochondral articular lining textile 10 (e.g., the osteoconductive layer 18) can be accomplished using any one or combination of sutures, staples, thermal methods,chemical methods (e.g., solvents or resins), a Velcro-like interface (e.g., hooks and loops, such as anchor hooks printed on the bone backing), and other means of mechanical fixation.

[0135] The osteoconductive bone backing 28 can be formed from one or more materials as discussed elsewhere herein. Additionally, the osteoconductive bone backing 28 can have a surface area, size, shape, and / or dimension identical to, or substantially identical to, the osteochondral articular lining textile 10 to which it is coupled or attached such that the combined textile 10 and bone backing 28 is appropriately configured for treatment of a particular cartilage defect, lesion or injury. For example, the artificial implant 11 can be provided in a form (e.g., a sheet form) that is readily shaped (e.g., by folding, cutting, trimming etc.) for administration to a particular cartilage defect. Alternatively, virtual surgical planning can be used to determine optimal dimensions of the artificial implant 11 based on patient-specific imaging data, e.g., based on the dimensions of a particular cartilage defect to be treated. In such instances, techniques for preparing the artificial implant 1 1 can include, for example, additive manufacturing techniques (e.g., 3D printing, such as extrusion-based bioprinting, inkjet bioprinting, and laser-assisted bioprinting).

[0136] Although not shown, it will be appreciated that an alternative construction of the artificial implant 1 1 can include all or only a portion of the articular layer 14 (e.g., the major surface 16) of the fabric scaffold 12 coupled or attached (e.g., directly attached) to the osteoconductive bone backing 28 (e.g., the first major surface 30).

[0137] Meniscus

[0138] In another aspect, a load-bearing component of the fully biologic replacement joint 2 (e.g., a knee) can comprise an engineered meniscus. Theengineered meniscus can comprise a resorbable collagen scaffold, for example, and be formulated to reproduce the correct stiffness and resilience of a recipient patient’s original hyaline cartilage. The engineered meniscus can also be configured to enable attachment of the meniscus to the underlying bone through ligamentous attachments. In one example, multiple layers of fabric scaffold 12 can be prepared and adhered on top of each other (e.g., chemically or thermally) to obtain a meniscus. The knitting pattern used to prepare the layers of fabric scaffold 12 can be programmed to have ligament like extensions for attaching the meniscus to the target joint.

[0139] Ligaments

[0140] In another aspect, a load-bearing component of the fully biologic replacement joint 2 (e.g., a knee) can comprise an engineered ligament (e.g., MCL, ACL, LCL, PCL). In one example, an engineered ligament can comprise a microporous ligamentous rope comprising woven collagen filaments. In some instances, distal and proximal end portions of an engineered ligament can be infused with HA to promote osteointegration. Additionally or optionally, the engineered ligament can be seeded with cells (as discussed below).

[0141] Load-bearing components of the fully biologic replacement joint 2 can be integrated or attached to one another using one or a combination attachment mechanisms. In one example, engineered articular cartilage 10 (e.g., OCALT) and an engineered osteoconductive scaffold (e.g., bone backing 28) can be integrated with, or attached to, one another using a Velcro-like attachment approach. Using this approach, OCALT 10 can be attached to the bone baking 28 by Velcro-like anchor hooks printed on the bone backing. In another example, an engineeredmeniscus can be attached to OCALT 10 by suturing. Other known means of mechanical fixation may also or alternatively be used.

[0142] Cells

[0143] In another aspect, the fully biologic replacement joint 2 of the present disclosure can comprise one or more mesenchymal progenitor cells (e.g., a mesenchymal stem cell or MSC) and / or differentiated primary cells (e.g., a chondrocyte) physically associated with at least one load-bearing structural component thereof. Mesenchymal progenitor cells and differentiated primary cells can be autologous or allogeneic. In one example, autologous mesenchymal progenitor cells and / or differentiated primary cells can be obtained from one or more donor-specific bone marrow biopsies. In another example, allogeneic mesenchymal progenitor cells (e.g., induced pluripotent stem cells, iPSCs) and / or differentiated primary cells can be obtained from a master cell bank, e.g., donor cell lines with known HLA profiles that match greater than 90% of the U.S. population and are homozygous at six sites.

[0144] Load-bearing structural components of the fully biologic replacement joint 2 can be seeded at an optimal cell density and distribution for consistency and uniformity.

[0145] Methods

[0146] Another aspect of the present disclosure can include a method for repairing, augmenting, or replacing a cartilage defect (e.g., damaged articular cartilage) in a subject. The method can comprise affixing an osteochondral articular lining textile 10 of the present disclosure (as illustrated in Figs. 1 A-D), or an artificial implant 11 (as illustrated in Figs. 1 E-H) to a surgically relevant site in order to repair, augment, or replace the cartilage defect (e.g., damaged articular cartilage). In oneexample, the method can include surgically implanting an artificial implant in place of a damaged articular cartilage, such as a focal defect in an impacted joint. In some embodiments, an osteochondral articular lining textile 10 (or artificial implant 11 ) is implanted into a subject at or near a site of a lesion, defect, injury and / or trauma, for example, at or near an articular surface, a chondral surface, or an osteochondral surface. Articular surfaces, for instance, that may be treated using the osteochondral articular lining textile 10 (or artificial implant 11 ) of the present disclosure can include articular surfaces of, for example, a knee, ankle, wrist, hip, elbow or shoulder.

[0147] In some instances, the osteochondral articular lining textile 10 (or the artificial implant 11 ) can be engineered to remain in place for as long as a treating physician deems necessary. As such, the rate of biodegradation of the fabric scaffold 12 can be separately engineered according to the needs of the particular surgery to be performed. For example, the fabric scaffold 12 can be engineered to have biodegraded between 6-18 months after implantation, such as for example 12 months.

[0148] In some embodiments, the osteochondral articular lining textile 10 (or the artificial implant 11 ) has a surface area, size, shape, and / or dimension appropriate for treatment of a particular cartilage defect, lesion or injury. For example, an osteochondral articular lining textile 10 (or artificial implant 11 ) can be provided in a form (e.g., a sheet form) that is readily shaped (e.g., by folding, cutting, trimming etc.) for administration to a particular cartilage defect. Alternatively, virtual surgical planning can be used to determine optimal dimensions of the osteochondral articular lining textile 10 (or artificial implant 11 ) based on patient-specific imaging data, e.g., based on the dimensions of a particular cartilage defect to be treated. In suchinstances, techniques for preparing the osteochondral articular lining textile 10 (or artificial implant 11 ) can include, for example, additive manufacturing techniques (e.g., 3D printing, such as extrusion-based bioprinting, inkjet bioprinting, and laser- assisted bioprinting).

[0149] As will be understood by one skilled in the art, the fabric scaffold 12 of the present disclosure can be designed having the physical properties of the cartilage (e.g., articular cartilage) to be repaired. Thus, the parameters of each physical characteristic (e.g., yield strength, elastic modulus, ultimate stress, fiber or thread diameter, pore diameter, permeability, etc.) can be designed according to the repair to be carried out. Moreover, each of these physical characteristics can be modified, as desired, to approximate the natural architecture of the articular cartilage to be repaired, augmented, or replaced by, for example, making the appropriate selection of polymer and / or polymer ratio, modification of the electrochemical compaction and / or knitting processes, selection of biocompatible ceramic materials for incorporation into the fabric scaffold 12, and selection of particular cell types and bioactive agent(s).

[0150] Another aspect of the present disclosure includes methods for preparing a fully biologic replacement joint 2 (e.g., an autologous or allogeneic biologic replacement joint) as well as methods for surgically implanting the fully biologic replacement joint.

[0151] For purposes of simplicity, the methods are shown and described as being executed serially; however, it is to be understood and appreciated that the present disclosure is not limited by the illustrated order as some steps could occur in different orders and / or concurrently with other steps shown and described herein. Moreover,not all illustrated aspects may be required to implement the method, nor is the method necessarily limited to the illustrated aspects.

[0152] In one aspect, a method 10 (Fig. 6) is provided for preparing a fully biologic replacement joint 2. As discussed in more detail below, the method 10 can comprise the steps of: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof (Step 12); assembling a plurality of the acellular, load-bearing structural components into an acellular joint (Step 14); seeding the acellular replacement joint 2 with one or more mesenchymal progenitor cells and / or differentiated primary cells to form a cellularized joint (Step 16); conditioning the cellularized joint to form the fully biologic replacement joint 2 (Step 18); surgically implanting the fully biologic replacement joint 2 (Step 20); and, optionally, storing the fully biologic replacement joint 2 (Step 22), e.g., prior to surgically implanting the fully biologic replacement joint.

[0153] At Step 12, one or more acellular, load-bearing structural components can be prepared. The composition and structure of particular load-bearing structural component(s) prepared at Step 12 will depend upon the particular joint(s) to be replaced. Techniques for preparing the load-bearing structural component(s) can include, for example, additive manufacturing techniques (e.g., 3D printing, such as extrusion-based bioprinting, inkjet bioprinting, and laser-assisted bioprinting). In certain aspects, virtual surgical planning can be used to determine optimal dimensions of the load-bearing structural component(s) based, e.g., on patientspecific imaging data. Also at Step 12, desired materials and material formulations, such as those discussed above (e.g., HA and PCL) for particular load-bearing structural component(s) can be selected.

[0154] At Step 14, a plurality of the acellular, load-bearing structural components can be assembled into an acellular joint. In one example, to assemble an acellular replacement knee joint, load-bearing structural components such as ligaments, menisci, articular cartilage, and an osteoconductive scaffold can be assembled as described herein.

[0155] Next, the assembled acellular replacement joint 2 can be cellularized with one or more mesenchymal progenitor cells and / or differentiated primary cells (Step 16) and then conditioned (Step 18) to form a cellularized joint. In one example, the assembled acellular replacement joint 2 can be cellularized by seeding one or all structural components thereof with mesenchymal progenitor cells and / or differentiated primary cells. Seeding can be done, for example, in a bioreactor, such as a BioBOT500 station or a custom-designed, 3D printed bioreactor. The mesenchymal progenitor cells and / or differentiated primary cells used for seeding can be obtained or derived, for example, from donor or recipient subjects (e.g., human or non-human subjects). The cells used at Step 16 can be expanded and / or differentiated into a target cell type (e.g., a chondrocyte or MSC) prior to seeding. One or more seeding protocols can be employed to optimize seeding density, perfusion rate, and time to achieve uniform seeding of cells.

[0156] MSCs, for example, can be expanded ex vivo using xeno-free or GMP- grade components and culture conditions. For instance, microcarriers can be used to expand MSCs in a vertical wheel bioreactor. Seeding density can be optimized using oxygen optodes on bioreactor walls and embedded in the microcarriers. Oxygen, glucose, and lactate can be monitored in-line, as well as the secretome to determine cell quality. Supplementation with FGF2, for example, can be done to preserve MSC phenotype and improve chondrogenic potential.

[0157] Chondrocytes, for example, can be expanded ex vivo in adherent cultures. Culture conditions can be optimized to reduce cell doubling time, e.g., to less than about 2 days. Doubling time can be minimized under the constraint of preserving cell phenotype by changing glucose and growth factor levels (e.g., FGF2, FGF9, FGF18, IGF, and TGF 1 ) in culture medium and incubator oxygen levels.

[0158] In one example, acellular load-bearing components of a fully biologic replacement knee can be cellularized as follows: chondral linings can be seeded with chondrocytes conditioned in custom- designed 3D printed bioreactors. Expanded chondrocytes (for an autologous fully biologic replacement joint 2) or iPSCs having been expanded differentiated into induced MSCs (iMSCs) (for an allogeneic fully biologic replacement joint 2) can be seeded onto collagen scaffolds using, e.g., a BioBGT500 station to achieve consistency and uniformity;PCL / HA scaffolds can be seeded with MSCs (for autologous) and iMSCs (for allogeneic); for ligaments, braided ropes (as discussed above) can be seeded with MSCs (for autologous) and iMSCs (for allogeneic) and differentiated in a suitable culture apparatus (e.g., CellScale); and

[0159] for meniscal components, MSCs (for autologous) and iMSCs (for allogeneic) can be carried out using a custom, 3D-printed seeding chamber based on patient-specific imaging data; whereafter, menisci can be cultured under dynamic compression using a spherical surface.

[0160] As noted, conditioning the cellularized joint (Step 18) can be done using a commercially available or custom-designed bioreactor that optimiz(es) compression, fluid shear, tension, and hydrostatic pressure cycling for optimal cartilage and boneengineering. In one example, a bioreactor can be utilized so as to subject cells / tissues to intermittent cyclic hydrostatic pressures and thereby increase compressive modulus of elasticity of the tissue(s) being conditioned. In some instances, bioreactors used at Step 18 can include oxygen, glucose, lactate, and acoustic (tissue integrity and mechanical property) sensors. As glucose uptake and lactate secretion are directly related to ECM synthesis rate, such sensors can be used to monitor tissue quality non-invasively. Also during Step 18, tissue can be cultured for a desired period of time (e.g., about two weeks to match the in vivo timeframe) and then be assessed for desired load-bearing and histology characteristics.

[0161] It will be appreciated that the order of Steps 14, 16 and 18, as depicted in Fig. 6, can be changed as desired. For example, acellular load-bearing structural components can be separately cellularized and then conditioned before assembly of a cellularized joint.

[0162] Following Step 18, the cellularized joint can be surgically implanted in a subject in need thereof (Step 20) or stored until needed (Step 22).

[0163] At Step 20, a fully biologic replacement joint 2 prepared according to the method 10 can be surgically implanted in a subject in need thereof (e.g., using known arthroplasty techniques), thereby restoring all tissue components of the joint that have degenerated. Advantageously, replacement of a dysfunctional or diseased joint using a fully biologic replacement joint 2 of the present disclosure improves quality of life for recipient patients by restoring natural mobility through anatomically correct regeneration of all the joint’s tissues, not just the cartilage.

[0164] In one example, a fully biologic replacement knee joint can be surgically implanted in place of a diseased or damaged knee joint of a subject using anapproach that includes not only known total knee arthroplasty (TKA) techniques, but also the use of magnesium-alloy implant attachment posts (described above). The posts, for example, can be used at distal femoral, internal patellar, and superior plateau surfaces. On one end, the posts can be integrated with the porous PCL-HA scaffold with sufficient strength to accept ambulatory load while bone forms in vivo. Unlike the current standard-of-care TKA, which includes large, relatively flat metal trays that replace much of the host bone of the condylar surface, the fully biologic replacement knee joint of the present disclosure has minimal depth and conforms to the subject’s condylar surface with a focus on integration with the host bone.

[0165] At Step 22, fully biologic replacement joints 2 prepared according to the method 10 can be stored using a storage protocol optimally tuned for preservation of the fully biologic replacement joints and their constitutive cells and tissues, inclusive of cells (e.g., chondrocytes, MSCs) and bioengineered ligaments and menisci. In one example, a fully biologic replacement joint 2 prepared according to the method 10 can be stored prior to surgically implanting the fully biologic replacement joint in a subject.

[0166] As shown in Fig. 7, another aspect of the present disclosure can include a method 30 for preparing an autologous, fully biologic replacement joint 2. It will be appreciated that certain steps of the method 30 are the same, or substantially the same, as those comprising the method 10 described above, in which case the same (or substantially the same) steps use the same reference numbers and steps that are different use different reference numbers.

[0167] Generally speaking, the method 30 can comprise the following steps: obtaining a three-dimensional image of a dysfunctional joint in a patient (Step 32); preparing at least one acellular, load-bearing structural component selected from thegroup consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof (Step 12); assembling a plurality of the acellular, load-bearing structural components into an acellular joint (Step 14); seeding the acellular joint with one or more mesenchymal progenitor cells and / or differentiated primary cells previously obtained from the patient to form a cellularized joint (Step 16); and conditioning the cellularized joint to form the autologous, fully biologic replacement joint 2. Advantageously, the method 30 can deliver a patient- customized, load-bearing biologic replacement joint 2 in less than 28 days. Other steps comprising the method 30 are described below and shown in Fig. 7.

[0168] Referring to Step 32, the method 30 can initially comprise obtaining a three-dimensional (3D) image of a dysfunctional (e.g., diseased) joint in a patient. In one example, virtual surgical planning can be used based on patient-specific imaging data (e.g., CT and / or MRI) to obtain the 3D image.

[0169] After a 3D image of the dysfunctional joint has been obtained, at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof, can be prepared at Step 12 (as discussed above). A plurality of the acellular, load-bearing structural components can then be assembled into an acellular joint (Step 14); whereafter, the acellular joint can be cellularized by seeding (the acellular joint) with one or more mesenchymal progenitor cells and / or differentiated primary cells previously obtained from the patient to form a cellularized joint (Step 16). At or about the same time, the cellularized joint can be conditioned at Step 18 (as described above) to form the autologous, fully biologic replacement joint 2.

[0170] Prior to Step 16, the method 30 can include the steps of harvesting cells from the patient in need of joint replacement (Step 34) and expanding and / or differentiating the harvested cells (Step 36).

[0171] At Step 34, cells (e.g., MSCs or mature parenchymal cells) from the patient can be harvested, e.g., via bone marrow from donor-specific biopsies.

[0172] At Step 36, harvested cells can be expanded and / or differentiated, as described above. MSCs, for example, can be expanded ex vivo using xeno-free or GMP-grade components and cell culture conditions. For instance, microcarriers can be used to expand MSCs in a vertical wheel bioreactor. Seeding density can be optimized using oxygen optodes on bioreactor walls and embedded in the microcarriers. Oxygen, glucose, and lactate can be monitored in-line, as well as the secretome to determine cell quality. Supplementation with FGF2, for example, can be done to preserve MSC phenotype and improve chondrogenic potential.

[0173] Additionally, chondrocytes can be expanded ex vivo in adherent cultures. Culture conditions can be optimized to reduce cell doubling time, e.g., to less than about 2 days. Doubling time can be minimized under the constraint of preserving cell phenotype by changing glucose and growth factor levels (e.g., FGF2, FGF9, FGF18, IGF, and TGF|31 ) in culture medium and incubator oxygen levels.

[0174] At Step 20, the autologous, fully biologic replacement joint 2 can be surgically implanted in the subject, as described above, thereby restoring all tissue components (not just the cartilage) of the joint that have degenerated in an anatomically correct manner and improving quality of life for recipient patients by restoring natural mobility.

[0175] It will be appreciated that the order of steps comprising the method 30 (e.g., Steps 14, 16 and 18) can be changed as desired. For example, acellular load-bearing structural components can be separately cellularized and then conditioned before assembly of a cellularized joint.

[0176] As shown in Fig. 8, another aspect of the present disclosure can include a method 40 for preparing an allogeneic, fully biologic replacement joint 2. It will be appreciated that certain steps of the method 40 are the same, or substantially the same, as those comprising the method 10 described above, in which case the same (or substantially the same) steps use the same reference numbers, and steps that are different use different reference numbers.

[0177] Generally speaking, the method 40 can comprise the following steps: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof (Step 12); assembling a plurality of the acellular, load-bearing structural components into an acellular joint (Step 14); seeding the acellular joint with one or more donor mesenchymal progenitor cells and / or differentiated primary cells obtained from a curated donor cell bank to form a cellularized joint (Step 16); conditioning the cellularized joint to form the allogeneic, fully biologic replacement joint 2 (Step 18); and storing the allogeneic, fully biologic replacement joint under conditions sufficient to substantially preserve the biological, functional, and structural viability of the allogeneic, fully biologic replacement joint (Step 22). Advantageously, the method 40 can deliver an allogeneic, load-bearing biologic replacement joint 2 within 1 day, thereby providing a rapid and effective solution for total joint arthroplasty. Other steps comprising the method 40 are described below and shown in Fig. 8.

[0178] Initially, Steps 12, 14, 16, and 18 of the method 40 can be performed as described above.

[0179] Prior to Step 16, the method 40 can include the steps of obtaining cells from a curated donor cell bank (Step 42) and expanding and / or differentiating the obtained cells (Step 44).

[0180] At Step 42, cells (e.g., iPSCs) can be obtained from a curated donor cell bank comprising donor cell lines with known HLA profiles that match greater than 90% of the U.S. population and are homozygous at six sites.

[0181] At Step 44, the obtained donor cells (e.g., iPSCs) can be expanded and differentiated into induced MSCs (iMSCs). In one example, iMSCs can be expanded in microcarrier suspension culture (e.g., in a bioreactor) to obtain approximately 250M cells per donor after about 8 doublings. Doubling time can minimized by monitoring bioreactor oxygen levels and also oxygen levels within the microcarriers along with computational fluid dynamic models to preserve iMSC phenotype. Expanded donor cells can be validated for trilineage differentiation potential.Validated cells can then be differentiated into preferred cell types or cryopreserved for further use.

[0182] Before, contemporaneous with, or following Step 18 - but before Step 22 - Steps 46 and 48 can be performed. At Step 46, blood from the patient in need of total joint replacement can be cross-matched with donor cell phenotype (e.g., HLA profile) (Step 46). At Step 48, the pertinent anatomy comprising a dysfunctional joint to be replaced can be cross-matched with the dimensions of the allogeneic fully biological replacement joint 2. This can be done, for example, using virtual surgical planning based on patient-specific imaging data (e.g., CT and / or MRI) to obtain a 3D image of the pertinent anatomy.

[0183] Following Step 18, the allogeneic fully biologic replacement joint 2 can be stored at a donor implant bank under conditions sufficient to substantially preservethe biological, functional, and structural viability of the allogeneic fully biologic replacement joint. In one example, a storage protocol optimally tuned for preservation of allogeneic fully biologic replacement joints 2 and their constitutive cells and tissues, inclusive of cells (e.g., iMSCs), and bioengineered ligaments and menisci can be employed. Advantageously, such storage protocol can extend the preservation limits of allogeneic tissue products to multiple months (e.g., 4 months or more) without significant impairment in their biological, functional, and structural viability.

[0184] At Step 20, the allogeneic fully biologic replacement joint 2 - having matching size and immunocompatibility as the recipient subject - can be surgically implanted in the recipient subject, thereby restoring all tissue components (not just the cartilage) of the joint that have degenerated in an anatomically correct manner and improving quality of life for recipient patients by restoring natural mobility.

[0185] In an alternative embodiment of the method 40, Step 46 can precede Step 44. For example, blood from a patient in need of total joint replacement can be cross-matched with donor cell phenotype (e.g., HLA profile); whereafter, obtained donor cells (e.g., iPSCs) can be expanded and differentiated into iMSCs. At or about the same time that Step 44 is performed, Steps 12 and 14 can be performed (e.g., to prepare PCL / HA bone backing by 3D printing). Next, Steps 16 and 18 can be performed (as described above) to cellularize or populate the bone backing with the expanded donor cells, which can then be matured in a bioreactor. The remaining Steps of the method 40 can then be performed as described above.

[0186] Exemplary Aspects

[0187] In view of the described compositions, devices, and methods and variations thereof, herein below are certain more particularly described aspects ofthe present disclosure. These particularly recited aspects should not, however, be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein, or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language literally used therein.

[0188] Aspect 1 : A knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold, the fabric scaffold comprising a plurality of biocompatible polymers having an alignment and orientation that supports the generation and growth of native cartilage; wherein the osteochondral articular lining textile is optionally coupled to an osteoconductive bone backing.

[0189] Aspect 2: The osteochondral articular lining textile of Aspect 1 , wherein the fabric scaffold further comprises: an articular layer having a major surface and being adapted to physically interface with a corresponding articular layer of a joint surface; an osteoconductive layer having a major surface and being adapted to anchor the osteochondral articular lining textile to a bone surface, the osteoconductive layer being continuous with the articular layer; and one or more interconnecting support components extending between the major surface of the articular layer and the major surface of the osteoconductive layer, the one or more interconnecting support components comprising a plurality of biocompatible polymers having an alignment and orientation that is different than the alignment and orientation of the biocompatible polymers comprising at least the articular layer.

[0190] Aspect 3: The osteochondral articular lining textile of any one of Aspects 1 -2, wherein the one or more interconnecting support components are located within only the articular layer.

[0191] Aspect 4: The osteochondral articular lining textile of any one of Aspects 1 -3, wherein the plurality biocompatible polymers is biodegradable, non- biodegradable, or a combination thereof, and is selected from the group consisting of synthetic polymers and / or natural polymers.

[0192] Aspect 5: The osteochondral articular lining textile of Aspect 4, wherein the natural polymer is collagen.

[0193] Aspect 6: The osteochondral articular lining textile of any one of Aspects 1 -5, wherein the plurality of biocompatible polymers is formulated as a structure selected from the group consisting of a microfiber, a nanofiber, a fiber, a thread, a yarn, a multifilament, and combinations thereof.

[0194] Aspect 7: The osteochondral articular lining textile of any one of Aspects 1 -6, wherein the osteoconductive layer further comprises a biocompatible ceramic.

[0195] Aspect 8: The osteochondral articular lining textile of Aspect 7, wherein the biocompatible ceramic is hydroxyapatite.

[0196] Aspect 9: The osteochondral articular lining textile of any one of Aspects 1 -8, wherein the plurality of biocompatible polymers comprising the one or more interconnecting support components have an alignment and orientation that is substantially orthogonal to the alignment and orientation of the biocompatible polymers comprising at least the articular layer.

[0197] Aspect 10: The osteochondral articular lining textile of any one of Aspects 1 -9, wherein all or only a portion of the fabric scaffold is cross-linked with a crosslinking agent.

[0198] Aspect 11 : The osteochondral articular lining textile of Aspect 10, wherein the cross-linking agent is genipin.

[0199] Aspect 12: The osteochondral articular lining textile of any one of Aspects 1-11 , wherein at least a portion of the fabric scaffold includes a population of cells physically associated therewith, the cells being selected from the group consisting of fibroblasts, chondrocytes, osteoblasts, osteoblast-like cells, stem or progenitor cells, and combinations thereof.

[0200] Aspect 13: The osteochondral articular lining textile of any one of Aspects 1 -12, wherein at least a portion of the fabric scaffold comprises a bioactive agent selected from the group consisting of an anti-infective, an extracellular matrix component, an antibiotic, bisphosphonate, a hormone, an analgesic, an antiinflammatory agent, a growth factor, an angiogenic factor, a chemotherapeutic agent, an anti-rejection agent, an RGD peptide, and combinations thereof.

[0201] Aspect 14: The osteochondral articular lining textile of any one of Aspects 1 -13, having an elastic modulus of about 0.2 MPa to about 10 MPa.

[0202] Aspect 15: The osteochondral articular lining textile of any one of Aspects 1 -14, having a thickness of about 1 mm to about 5 mm.

[0203] Aspect 16: The osteochondral articular lining textile of any one of Aspects 1 -15, being non-woven.

[0204] Aspect 17: A method for repairing, augmenting, or replacing damaged articular cartilage in a patient comprising affixing the osteochondral articular lining textile of any one of Aspects 1 -16 to a surgically relevant site in order to repair, augment, or replace the damaged articular cartilage; wherein the osteochondral articular lining textile is optionally coupled to an osteoconductive bone backing.

[0205] Aspect 18: An artificial joint comprising a three-dimensional, osteoconductive bone backing and the osteochondral articular lining textile of any one of Aspects 1 -16, which is coupled to the osteoconductive bone backing.

[0206] Aspect 19: A method for replacing a damaged joint in a patient comprising surgically implanting the artificial joint of Aspect 18 in place of the damaged joint.

[0207] Aspect 20: A fully biologic replacement joint comprising: at least one load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; and one or more mesenchymal progenitor cells and / or differentiated primary cells physically associated with the at least one load-bearing structural component.

[0208] Aspect 21 : The fully biologic replacement joint of Aspect 20, wherein the osteoconductive scaffold is adapted to fixedly receive one or more resorbable, osteogenic anchoring posts.

[0209] Aspect 22: The fully biologic replacement joint of any one of Aspects 20- 21 , comprising a complete or partial knee joint, a complete or partial shoulder joint, a complete or partial hip joint, a complete or partial joint comprising a hand (e.g., a complete or partial finger joint), a complete or partial elbow joint, a complete or partial joint comprising a foot (e.g., a complete or partial toe joint), a complete or partial neck joint, a complete or partial joint comprising an ankle, a complete or partial temporomandibular joint, or a complete or partial joint comprising a wrist joint (e.g., a complete or partial radiocarpal joint).

[0210] Aspect 23: The fully biologic replacement joint of any one of Aspects 20- 23, wherein the one or more mesenchymal progenitor cells and / or differentiated primary cells is autologous or allogeneic.

[0211] Aspect 24: The fully biologic replacement joint of any one of Aspects 20- 23, wherein the one or more mesenchymal progenitor cells and / or differentiated primary cells is a mesenchymal stem cell or a chondrocyte.

[0212] Aspect 25: The fully biologic replacement joint of any one of Aspects 20- 24, wherein the articular cartilage comprises the osteochondral articular lining textile of any one of Aspects 1 -16.

[0213] Aspect 26: A method for preparing a fully biologic replacement joint, the method comprising: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular replacement joint with one or more mesenchymal progenitor cells and / or differentiated primary cells to form a cellularized joint; and conditioning the cellularized joint to form the fully biologic replacement joint.

[0214] Aspect 27: A method for preparing an autologous, fully biologic replacement joint, the method comprising: obtaining a three-dimensional image of a dysfunctional joint in a patient; preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more mesenchymal progenitor cells and / or differentiated primary cells previously obtained from the patient to form a cellularized joint; and conditioning the cellularized joint to form the autologous, fully biologic replacement joint.

[0215] Aspect 28: A method for preparing an allogeneic, fully biologic replacement joint, the method comprising: preparing at least one acellular, loadbearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof;assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more donor mesenchymal progenitor cells and / or differentiated primary cells obtained from a curated donor cell bank to form a cellularized joint; conditioning the cellularized joint to form the allogeneic, fully biologic replacement joint; and storing the allogeneic, fully biologic replacement joint under conditions sufficient to substantially preserve the biological, functional, and structural viability of the allogeneic, fully biologic replacement joint.

[0216] Aspect 29: The method of Aspect 28, wherein storing the allogeneic, fully biologic replacement joint optionally includes cross-matching blood of a patient in need of the allogeneic, fully biologic replacement joint with the one or more mesenchymal progenitor cells comprising the allogeneic, fully biologic replacement joint.

[0217] Aspect 30: A fully biologic replacement joint prepared according to any one of Aspects 26-29.

[0218] Aspect 30: A method for replacing a dysfunctional joint in a patient comprising surgically implanting the fully biologic replacement joint of any one of Aspects 20-29.

[0219] Aspect 31 : A knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold, the fabric scaffold comprising a plurality of biocompatible polymers having an alignment and orientation that supports the generation and growth of native cartilage; wherein the osteochondral articular lining textile is coupled to an osteoconductive bone backing.

[0220] Aspect 32: A method for repairing, augmenting, or replacing damaged articular cartilage in a patient comprising affixing the osteochondral articular liningtextile of Aspect 31 to a surgically relevant site in order to repair, augment, or replace the damaged articular cartilage.

[0221] Aspect 33: The method of Aspect 32, wherein the damaged articular cartilage comprises a defect, such as a focal defect or a partial joint defect.

[0222] Aspect 34: An artificial implant comprising a three-dimensional, osteoconductive bone backing coupled to the osteochondral articular lining textile of any one of Aspects 1-16, wherein the artificial implant is sized and dimensioned to repair, augment or replace a damaged articular cartilage in a localized portion of an impacted joint.

[0223] Aspect 35: A method for repairing, augmenting or replacing damaged articular cartilage in a patient, the method comprising surgically implanting the artificial implant of Aspect 34 in place of the damaged articular cartilage.

[0224] The following Example is for the purpose of illustration only and is not intended to limit the scope of the claims, which are appended hereto.Example

[0225] Experiments were performed to investigate structural and mechanical properties of osteochondral articular lining textiles constructed in accordance with one embodiment of the present disclosure.

[0226] Collagen monofilaments have flat cross section, and their width should be reduced to increase knitting efficiency. As shown in Fig. 11 , fibers were spun to reduce dimension (single-ply spun and two-ply spun). Spinning and plying were performed by a motorized spinner. Flat monofilament, plied monofilament, and 2-ply yarn’s width were measured from images. Flat monofilament, plied monofilament, and 2-ply yarn’s tensile strengths were measured.

[0227] As shown in Figs. 12A-B, flat monofilaments width reduces by 2.7-fold following spinning. The cross-section became rounder with spinning. And the width of 2-ply yarns were twice as small as the flat monofilaments. Additionally, spun monofilaments (1 -ply) had 40% lower tensile strength than flat monofilaments. And two-ply yarns had 30% greater strength than flat monofilaments, and two-fold greater strength than spun 1 -ply monofilaments.

[0228] One example of a knitting method is described below.

[0229] Step 1 - design

[0230] Create the osteochondral articular lining textiles architecture with desired shape and size in Create Plus software by STOLL and KM. ON.

[0231] Step 2 - send to machine

[0232] Export the program and load it onto the Stoll CMS two-bed weft knitting machine.

[0233] Step 3 - load and assign yarns

[0234] Prepare the yarn by plying (especially for collagen). Transfer the plyed yarn into the bobbin. Load the yarn’s spool (bobbin) on the machine and hook on the yarn carriers. In our case following carrier number is assigned for different face of the osteochondral articular lining textiles: Yarn Carrier #4: Articular Face (Top Layer); Yarn Carrier #5: Spacer / Vertical Connector (Middle); and Yarn Carrier #6: Bone Face (Bottom Layer). Materials are interchangeable; PCL, PLGA, or collagen can be assigned per face (all same, or mixed) to tune properties in the Yarn Carrier #4-6.

[0235] Step 4 - knit

[0236] Check settings: stitch length, take-down, and carriage speed. Start production: the carriage moves the yarn carriers through the knitting zone. Themachine knits the two faces and the spacer connectors across the front and rear needle beds per the program. Temporary yarns for stable take-down: Carrier #8: waste (residual) yarn; and Carrier #2: brown binding yarn that ties the fabric to the waste (both are removed after knitting).

[0237] Step 5 - finish

[0238] Cut away the waste sections and pull out the binding yarn. Inspect, trim edges, and (optionally) condition the fabric. The osteochondral articular lining textile is now ready for use.

[0239] Effects of threads plying and spinning in the fabric appearance and porosity

[0240] As shown in Figs. 13-14, double jersey structure was knitted with an industrial grade knitting machine, both for 0.3 mm and 0.8 mm width collagen fibers. Spun monofilaments provided better knit structure than flat monofilament. Despite lower tensile strength, 0.3 mm thread knitted better than the wider thread. There were breakages / defects in 0.8 mm (red arrowheads, Fig. 13). Advantages of the reduced width include: improves knitting; results in a finer grain; greater surface for cell attachment; and cost saving by less collagen usage. Advantageously, width and length can be specified to any value for future GMP production, e.g., ovine joint surface 75 cm2(~9x9 cm) or human joint surface 160 cm2(~13x13 cm).

[0241] Osteochondral articular lining textile: Multi-Material Knitting

[0242] Fig. 15 illustrates successful knitting of an osteochondral articular lining textile using collagen and POL. The fabricated osteochondral articular lining textile was comprised as follows: articular Face = Spun 2 ply collagen fiber; bone face = PCL monofilament; and vertical connectors = spun collagen plied with PCLmonofilament. Knit density can be adjusted by needle tension (Red: Loose, Blue: Tight, Fig. 15).

[0243] Fig. 16 shows different knitting iterations (left to right) in the osteochondral articular lining textile. Angle of spacer threads becoming more oblique from left to right. Same number of spacer threads between layers. But longer distance, resulting in greater thread amount (increased padding) and increased fabric thickness.

[0244] Referring to Figs. 17-18, osteochondral articular lining textiles were knitted using PLGA yarns in the spacer and bone interface with PCL and / or collagen in the articular face / layer to increase the mechanical properties. Different diameters of the yarns were used to knit the osteochondral articular lining textiles, e.g., PCL (90, 180, and 225 pm) and PLGA (110 and 150 pm) (Fig. 17). PLGA improves the compressive strength of the osteochondral articular lining textiles (Fig. 18). Modulus can be altered by using different material or different size of the yarns.

[0245] Referring to Fig. 19, three different types of knitting patterns were explored: Vertical - No Skip, Vertical Skip, and Oblique. These patterns were fabricated and tested with all the yarns in the osteochondral articular lining textiles were PCL monofilaments (180 microns). Additionally, Vertical no skip and oblique patterns were knitted using full 2-ply collagen spacer and collagen articular layers. Testing was done in unconfined compression and aggregate modulus, Young’s modulus, and Shear moduli along and across the knitting direction were recorded.

[0246] Mechanical results

[0247] Referring to Figs. 20A-D, compared to oblique, vertical orientation, has greater aggregate modulus and Young’s modulus and no change in shear modulus was observed. Using PCL as a spacer filament as opposed to collagen filaments,substantially greater aggregate or young’s moduli and no change in shear moduli were observed. Aggregate modulus values of all PCL osteochondral articular lining textiles matched / exceeded that of ovine cartilage. Young’s moduli values of all PCL osteochondral articular lining textiles matched tibial cartilage but lower than femoral or patellar cartilage. Shear moduli values of all osteochondral articular lining textiles variations match tibial cartilage of ovine, but lower than femoral and patellar values.

[0248] Porosity

[0249] Referring to Figs. 21 -22, average pore size of different PCL / Collagen osteochondral articular lining textiles in articular surface and bone interface were measured using stereomicroscope. Gravimetric method was used to measured the porosity of fabric when integrated on a membrane as follows: 3D printed mold of same dimensions as osteochondral articular lining textile; weigh dry fabric; add water to ensure fabric is filled to very top of fabric; weigh total amount; and use formula below to calculate % porosity:Total wt — Fabric wt% Po ro sity = - - - - - x 100Total wt

[0250] The osteochondral articular lining textile’s high, interconnected porosity (-63-78%) (Fig. 23) with ~200- 400 pm pores provides open pathways for cell infiltration and nutrient transport, supporting cartilage ingrowth.

[0251] Monotonic tension

[0252] Two formulations, PLGA-based & Collagen-PCL based, were tested on monotonic tension, the results of which are shown in Figs. 24-26. Both PLGA and PCL-collagen based osteochondral articular lining textiles meet the tensile properties of native cartilage (base modulus > 1 MPa, >50% strength of native cartilage).

[0253] Fatigue

[0254] A custom fatigue machine was designed and fabricated (as shown in Fig., 27). It applies cyclic loading in compression and shear due to its slanted design. Fabrics were loaded up to 20% strain using displacement control for 1 million cycles. Some samples experienced increase in Young’s modulus after fatigue due to settling of the fabrics over time. As shown in figs. 28A-B, average modulus degradation of PCL-Collagen and PLGA OCALT did not exceed 10% for both compression and shear.

[0255] From the above description of the present disclosure, those skilled in the art will perceive improvements, changes and modifications. Such improvements, changes, and modifications are within the skill of those in the art and are intended to be covered by the appended claims. All patents, patent applications, and publications cited herein are incorporated by reference in their entirety.

Claims

CLAIMSThe following is claimed:1 . A knitted, multiphase osteochondral articular lining textile comprising a fabric scaffold, the fabric scaffold comprising a plurality of biocompatible polymers having an alignment that supports the generation and growth of native cartilage; wherein the osteochondral articular lining textile is optionally coupled to an osteoconductive bone backing.

2. The osteochondral articular lining textile of claim 1 , wherein the fabric scaffold further comprises: an articular layer having a major surface and being adapted to physically interface with a corresponding articular layer of a joint surface; an osteoconductive layer having a major surface and being adapted to anchor the osteochondral articular lining textile to a bone surface, the osteoconductive layer being continuous with the articular layer; and one or more interconnecting support components extending between the major surface of the articular layer and the major surface of the osteoconductive layer, the one or more interconnecting support components comprising a plurality of biocompatible polymers having an alignment and orientation that is different than the alignment and orientation of the biocompatible polymers comprising at least the articular layer.

3. The osteochondral articular lining textile of claim 2, wherein the one or more interconnecting support components are located within only the articular layer.

4. The osteochondral articular lining textile of claim 1 , wherein the plurality of biocompatible polymers is biodegradable, non-biodegradable, or a combination thereof, and is selected from the group consisting of synthetic polymers and / or natural polymers.

5. The osteochondral articular lining textile of claim 4, wherein the natural polymer is collagen.

6. The osteochondral articular lining textile of claim 1 , wherein the plurality of biocompatible polymers is formulated as a structure selected from the group consisting of a microfiber, a nanofiber, a fiber, a thread, a yarn, a multifilament, and combinations thereof.

7. The osteochondral articular lining textile of claim 2, wherein the osteoconductive layer further comprises a biocompatible ceramic.

8. The osteochondral articular lining textile of claim 7, wherein the biocompatible ceramic is hydroxyapatite.

9. The osteochondral articular lining textile of claim 2, wherein the plurality of biocompatible polymers comprising the one or more interconnecting support components have an alignment and orientation that is substantially orthogonal to the alignment and orientation of the biocompatible polymers comprising at least the articular layer.

10. The osteochondral articular lining textile of claim 1 , wherein all or only a portion of the fabric scaffold is cross-linked with a cross-linking agent.11 . The osteochondral articular lining textile of claim 10, wherein the crosslinking agent is genipin.

12. The osteochondral articular lining textile of claim 1 , wherein at least a portion of the fabric scaffold includes a population of cells physically associated therewith, the cells being selected from the group consisting of fibroblasts, chondrocytes, osteoblasts, osteoblast-like cells, stem or progenitor cells, and combinations thereof.

13. The osteochondral articular lining textile of claim 1 , wherein at least a portion of the fabric scaffold comprises a bioactive agent selected from the group consisting of an anti-infective, an extracellular matrix component, an antibiotic, bisphosphonate, a hormone, an analgesic, an anti-inflammatory agent, a growth factor, an angiogenic factor, a chemotherapeutic agent, an anti-rejection agent, an RGD peptide, and combinations thereof.

14. The osteochondral articular lining textile of claim 1 , having an elastic modulus of about 0.2 MPa to about 10 MPa.

15. The osteochondral articular lining textile of any one of claim 1 , having a thickness of about 1 mm to about 5 mm.

16. The osteochondral articular lining textile of claim 1 , being non-woven.

17. A method for repairing, augmenting, or replacing damaged articular cartilage in a patient comprising affixing the osteochondral articular lining textile of claim 1 to a surgically relevant site in order to repair, augment, or replace the damaged articular cartilage; wherein the osteochondral articular lining textile is optionally coupled to an osteoconductive bone backing.

18. An artificial joint comprising a three-dimensional, osteoconductive bone backing and the osteochondral articular lining textile of claim 1 , which is coupled to the osteoconductive bone backing.

19. A method for replacing a damaged joint in a patient comprising surgically implanting the artificial joint of claim 18 in place of the damaged joint.

20. A fully biologic replacement joint comprising: at least one load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; and one or more mesenchymal progenitor cells and / or differentiated primary cells physically associated with the at least one load-bearing structural component.21 . The fully biologic replacement joint of claim 20, wherein the osteoconductive scaffold is adapted to fixedly receive one or more resorbable, osteogenic anchoring posts.

22. The fully biologic replacement joint of claim 20, comprising a complete or partial knee joint, a complete or partial shoulder joint, a complete or partial hip joint, a complete or partial joint comprising a hand (e.g., a complete or partial finger joint), a complete or partial elbow joint, a complete or partial joint comprising a foot (e.g., a complete or partial toe joint), a complete or partial neck joint, a complete or partial joint comprising an ankle, a complete or partial temporomandibular joint, or a complete or partial joint comprising a wrist joint (e.g., a complete or partial radiocarpal joint).

23. The fully biologic replacement joint of claim 20, wherein the one or more mesenchymal progenitor cells and / or differentiated primary cells is autologous or allogeneic.

24. The fully biologic replacement joint of claim 20, wherein the one or more mesenchymal progenitor cells and / or differentiated primary cells is a mesenchymal stem cell or a chondrocyte.

25. The fully biologic replacement joint of claim 20, wherein the articular cartilage comprises the osteochondral articular lining textile of claim 1 .

26. A method for preparing a fully biologic replacement joint, the method comprising: preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof;assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular replacement joint with one or more mesenchymal progenitor cells and / or differentiated primary cells to form a cellularized joint; and conditioning the cellularized joint to form the fully biologic replacement joint.

27. A method for preparing an autologous, fully biologic replacement joint, the method comprising: obtaining a three-dimensional image of a dysfunctional joint in a patient; preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more mesenchymal progenitor cells and / or differentiated primary cells previously obtained from the patient to form a cellularized joint; and conditioning the cellularized joint to form the autologous, fully biologic replacement joint.

28. A method for preparing an allogeneic, fully biologic replacement joint, the method comprising:preparing at least one acellular, load-bearing structural component selected from the group consisting of ligaments, menisci, articular cartilage, an osteoconductive scaffold, and combinations thereof; assembling a plurality of the acellular, load-bearing structural components into an acellular joint; seeding the acellular joint with one or more donor mesenchymal progenitor cells and / or differentiated primary cells obtained from a curated donor cell bank to form a cellularized joint; conditioning the cellularized joint to form the allogeneic, fully biologic replacement joint; and storing the allogeneic, fully biologic replacement joint under conditions sufficient to substantially preserve the biological, functional, and structural viability of the allogeneic, fully biologic replacement joint.

29. The method of claim 28, wherein storing the allogeneic, fully biologic replacement joint optionally includes cross-matching blood of a patient in need of the allogeneic, fully biologic replacement joint with the one or more mesenchymal progenitor cells comprising the allogeneic, fully biologic replacement joint.

30. A fully biologic replacement joint prepared according to any one of claims 26-29.31 . A method for replacing a dysfunctional joint in a patient comprising surgically implanting the fully biologic replacement joint of any one of claims 20-29.

32. An artificial implant comprising a three-dimensional, osteoconductive bone backing coupled to the osteochondral articular lining textile of claim 1 , wherein the artificial implant is sized and dimensioned to repair, augment or replace a damaged articular cartilage in a localized portion of an impacted joint.

33. A method for repairing, augmenting or replacing damaged articular cartilage in a patient, the method comprising surgically implanting the artificial implant of claim 32 in place of the damaged articular cartilage.

Images