Implants for cartilage and related devices and methods

Abstract

The present disclosure relates to a transplantable implant comprising a biocompatible scaffold that degrades over time after implantation into a patient's cartilage; the biocompatible scaffold comprises a plurality of pores, and a plurality of chondrocytes are embedded in the scaffold. In some embodiments, the implant has a longitudinal length and is configured to be implanted in an implantation hole formed in the cartilage; wherein the implantation hole has an implantation depth, and a ratio of a full length of the longitudinal length to a thickness of the cartilage is 3 or less.

Description

Technical Field

[0001] This invention relates to an implant, and related apparatus and methods thereof; particularly to an implant for cartilage, and related apparatus and methods thereof. Background Technology

[0002] Cartilage is a flexible connective tissue found throughout the body, particularly in joints, where it provides cushioning and facilitates smooth movement. Cartilage plays a vital role in joint health by providing a smooth, low-friction surface to promote movement between bones and acting as a shock-absorbing structure during physical activity. Cartilage can be damaged by acute injuries, such as sports-related accidents, or by gradual wear and tear with age, often leading to conditions such as osteoarthritis. Surgical techniques such as cartilage grafts and autologous chondrocyte implantation have become options for repairing damaged cartilage, helping to alleviate pain and restore function while postponing the need for more invasive surgeries such as joint replacement. Because cartilage lacks a blood supply and has limited self-healing capacity, damage or wear has become a subject of medical research. In some cases, cartilage implants are used, designed to at least partially replace or repair worn cartilage and reduce joint pain, potentially offering a treatment option for conditions such as osteoarthritis. Summary of the Invention

[0003] This invention provides a simplified overview of several concepts, which may be further elaborated in the embodiments described below. This invention is not intended to define the key points or essential features of the claimed objectives.

[0004] In the exemplary embodiments described in this disclosure, all describable features that are not mutually exclusive can be combined with each other. Components of one embodiment may be used in other embodiments without further description. Other aspects and features of the invention will become apparent to those skilled in the art upon comparison with the accompanying drawings and descriptions of specific embodiments herein.

[0005] In some aspects, this disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after implantation into the cartilage of a patient; the biocompatible scaffold including a plurality of pores; a plurality of chondrocytes embedded in the scaffold; wherein the implant is for implantation into an implantation pore formed in the cartilage and has a longitudinal length; wherein the implantation pore has an implantation depth; wherein, when the implant is implanted into the implantation pore, the implant has a first longitudinal length along its entire longitudinal length corresponding to a cartilage portion in the implantation pore along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation pore along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least 0.3.

[0006] In some aspects, this disclosure relates to a transplantable implant wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least 0.5. In some aspects, this disclosure relates to a transplantable implant wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least 0.6. In some aspects, this disclosure relates to a transplantable implant wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most 0.8.

[0007] In some aspects, this disclosure relates to a transplantable implant, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.3 to 1. In some aspects, this disclosure relates to a transplantable implant, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.35 to 0.9. In some aspects, this disclosure relates to a transplantable implant, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.4 to 0.8. In some aspects, this disclosure relates to a transplantable implant, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.42 to 0.8. In some aspects, this disclosure relates to a transplantable implant, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.45 to 0.8.

[0008] In some aspects, this disclosure relates to a transplantable implant wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.45 to 0.7. In other aspects, this disclosure relates to a transplantable implant wherein the ratio of the first longitudinal length to the total length of the longitudinal length is 0.5 to 0.7.

[0009] In some aspects, this disclosure relates to a transplantable implant, wherein the implant is for insertion into an implantation hole formed in cartilage and has a longitudinal length of 12 mm or less. In some aspects, this disclosure relates to a transplantable implant, wherein the implant is for insertion into an implantation hole formed in cartilage and has a longitudinal length of 11 mm or less. In some aspects, this disclosure relates to a transplantable implant, wherein the implant is for insertion into an implantation hole formed in cartilage and has a longitudinal length of 10 mm or less. In some aspects, this disclosure relates to a transplantable implant, wherein the implant is for insertion into an implantation hole formed in cartilage and has a longitudinal length of 9 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 8.5 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 8.0 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 6.0 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 5.5 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 5.0 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 4.8 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal dimension is 4.7 mm or less. In some aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal length is 4.6 mm or less. In other aspects, this disclosure relates to a transplantable implant wherein the total length of the longitudinal length is 4.5 mm or less.

[0010] In some respects, this disclosure relates to a transplantable implant, wherein the biocompatible scaffold has a longitudinal length that is longer than a cartilage thickness.

[0011] In some aspects, this disclosure relates to a transplantable implant wherein the biocompatible scaffold has a porosity of at least 60%. In some aspects, this disclosure relates to a transplantable implant wherein the biocompatible scaffold has a porosity of at least 65%. In some aspects, this disclosure relates to a transplantable implant wherein the biocompatible scaffold has a porosity of at least 75%.

[0012] In some aspects, this disclosure relates to a transplantable implant wherein the average size of the plurality of pores is from 100 µm to 700 µm. In other aspects, this disclosure relates to a transplantable implant wherein the average size of the plurality of pores is from 225 µm to 450 µm.

[0013] In some aspects, this disclosure relates to a transplantable implant wherein the plurality of chondrocytes comprises a plurality of autologous chondrocytes. In some aspects, this disclosure relates to a transplantable implant wherein the biocompatible scaffold comprises poly-L-lactic-co-glycolic acid (PLGA). In some aspects, this disclosure relates to a transplantable implant wherein the biocompatible scaffold comprises calcium triphosphate (TCP). Attached Figure Description

[0014] Figure 1A In some embodiments, an implantation site for the osteochondral defect is formed by drilling a hole in the center of the weight-bearing portion on the surface of the distal femoral condyle.

[0015] Figure 1B In some embodiments shown, a modified cylindrical plug was inserted into the defect at the implantation site, which was used as the test group, and was flush with the articular surface.

[0016] Figure 2A The following are examples of untrimmed cylindrical grafts used in a method for preparing trimmed cylindrical grafts, as shown in certain embodiments.

[0017] Figure 2B An example trimming apparatus for a method of preparing trimmed cylindrical grafts is shown in some embodiments.

[0018] Figure 2C Examples of structures and processes for the preparation and implantation of transplantable implants according to at least some aspects of this disclosure are shown in certain embodiments.

[0019] Figure 3 The images shown are computed tomography (CT) images of animals with cartilage defects at 1 month, 6 months, and 12 months post-surgery in some embodiments.

[0020] Figure 4 The bone volume to total volume (BV / TV) ratio of osteochondral defects in 12-month CT images is shown in some embodiments.

[0021] Figure 5 The images shown are magnetic resonance imaging (MR) images of animals with cartilage defects 12 months after surgery, in some embodiments.

[0022] Figure 6AThe images show the gross appearance of cartilage in animals with trimmed cylindrical grafts after sacrifice in some embodiments.

[0023] Figure 6B The images show the gross appearance of cartilage in the hollow-hole group animals after sacrifice in some embodiments.

[0024] Figure 7A and Figure 7B The images show hematoxylin-eosin (H&E) staining of cartilage defect animals in the modified cylindrical graft group and the hollow group 12 months postoperatively in some embodiments.

[0025] Figures 8A to 8F Histological staining of animals with cartilage defects 12 months after surgery is shown in some embodiments.

[0026] Figures 9A to 9D Immunohistochemical staining of animals with cartilage defects 12 months after surgery is shown in some embodiments.

[0027] Figure 10A The images show the gross appearance of cartilage in animals with cartilage defects 12 months post-surgery, before and after compression.

[0028] Figure 10B The load-displacement curves of animals with cartilage defects 12 months after surgery are shown in some embodiments.

[0029] Figure 10C The stress-strain curves of animals with cartilage defects 12 months after surgery are shown in some embodiments. Detailed Implementation

[0030] The articles “a,” “an,” and “any” used in this article refer to one or more grammatically (e.g., at least one). For example, “an element” refers to one or more elements.

[0031] In the context of this specification and the scope of this patent application, the term "bottom" used to describe the location of a structure does not specifically refer to the bottom surface or end of the structure, but rather to the bottom surface or end of the structure and various locations adjacent to the lowest point, excluding the area above the horizontal center of the structure; and "top" does not refer only to the single, specific surface or end of the top of the structure, but rather to the top surface or end of the structure and various locations adjacent to the highest point, excluding the area below the horizontal center of the structure.

[0032] In this disclosure, the term "inner" used to describe the location of a structure refers to a location close to the center of the structure or a location that is not exposed; the term "outer" refers to a location far from the center of the structure or a location that is exposed.

[0033] In this specification, the term "on" (e.g., "on a component", "on the surface of a component") used to describe the location of a structure refers to any surface location of the structure, rather than the directional "above" or "over".

[0034] In this specification, the terms "fixed" and "arranged" used to describe structural assembly relationships generally refer to multiple structures that are not easily separated or detached after assembly. This relationship can be a fixed connection, a detachable connection, a one-piece connection, a mechanical connection, an electrical connection, a direct physical connection, or an indirect connection via an intermediary medium, such as any combination of threads, tenons, fasteners, nails, adhesives, or high-period joints.

[0035] In this specification, the term "pivot" used to describe structural assembly refers to a combination of hinges, cylinders, spheres, holes or slots, or bearings between multiple structures that can be assembled together, allowing the multiple structures to rotate or slide freely within a limited range without being easily separated or detached.

[0036] In this specification, the term "formation" used to describe structural assembly generally refers to the combination of one or more structures into a whole during the manufacturing process, or the creation of the same main structure due to different positions, shapes and corresponding functions.

[0037] When the knee joint undergoes degenerative disease, defects in the articular cartilage occur, affecting the range of motion and stiffness of the knee. Full-thickness defects cause discomfort, swelling, pain, and soreness in the knee, impacting daily activities. It is reported that the incidence of degenerative knee disease is approximately 29.1% in men and 41.5% in women, affecting an estimated 500 million people worldwide. Risk factors for knee degeneration include age, sex, obesity, genetics, and joint injury or overuse. The main functions of articular cartilage are mechanical support and physical protection. It can withstand pressure from the contralateral bones and release this pressure through its elasticity and expandability; it also protects the underlying bone from direct contact with the contralateral bones and provides lubrication, allowing bones to slide and the joint to move smoothly. However, because cartilage is avascular tissue and lacks repair cells, its healing capacity is extremely limited. Therefore, mosaickling and autologous chondrocyte implantation (ACI) were developed and have become the mainstream cell therapy methods for knee cartilage repair.

[0038] Cartilage, lacking a blood supply, has limited self-repair capabilities, making damage or wear a subject of medical research. In some embodiments, cartilage implants can be used. The purpose of such implants is to at least partially replace or repair worn cartilage and alleviate joint pain, potentially providing a treatment option for conditions such as osteoarthritis. In some embodiments, integration of the implant with surrounding tissues is crucial to its success, involving complex biological processes similar to those observed in bone implant integration.

[0039] For example, articular cartilage, which forms at the ends of joints or on the surface of bones, is a multifunctional tissue. Its elastic properties cushion impacts, lubricate bone surfaces with a low coefficient of friction, and allow for smooth and free movement between bones. The cells that make up cartilage, called chondrocytes, account for approximately 2% of the weight of articular cartilage and are enveloped in a large amount of extracellular matrix. A key difference between articular cartilage and other tissues is that it lacks blood vessels, lymphatic vessels, and nerves. The metabolic rate of cartilage is much slower than that of other tissues, making spontaneous healing of cartilage defects extremely difficult. Because there are no nerve endings in articular cartilage, patients with articular cartilage defects may not experience pain. The chondrocytes, enveloped in the cellular matrix, are well-differentiated cells with low proliferative capacity. Furthermore, due to the lack of blood vessels and lymphatic vessels in cartilage, mesenchymal stem cells cannot be induced or migrate to the damaged area.

[0040] In some embodiments, articular cartilage defects can be classified according to their severity as partial-thickness defects and full-thickness defects. Partial-thickness defects refer to damage or erosion of the articular cartilage tissue on the articular surface, but not reaching the subchondral bone; while full-thickness defects penetrate to the subchondral bone. In some embodiments, partial-thickness defects can be treated or their symptoms relieved through surgical or arthroscopic procedures, such as abrasion arthroplasty, debridement and lavage, and high tibial osteotomy. However, such surgeries may not be effective in treating severe injuries such as full-thickness defects. Therefore, patients often face the option of joint resection and replacement with an artificial joint to relieve pain and restore joint function. In the United States, an estimated more than 150,000 knee replacement surgeries are performed annually due to full-thickness defects, and this number is increasing year by year. Artificial joints and their replacement surgery are expensive, and metal artificial joints only last about 10 to 20 years. For younger patients, a second replacement surgery is almost inevitable; however, older patients may not be able to undergo a second replacement surgery and lose mobility for the rest of their lives. In some embodiments, the aim is to develop a new therapy for treating full-thickness cartilage defects.

[0041] In some embodiments, methods for treating full-thickness cartilage defects include microfracturing and drilling. This technique is a bone marrow-stimulating arthroscopic procedure used to penetrate the subchondral bone to induce the formation of a fibrin clot and promote the migration of primitive stem cells from the bone marrow to the cartilage defect site. More specifically, the base of the defect area is scraped or removed to induce bleeding, followed by the creation of small holes or microfractures in the subchondral bone plate using an arthroscopic awl or pick. During the procedure, the tip of the awl is manually tapped with a mallet to create these holes, taking care to avoid penetrating too deeply and damaging the subchondral plate. These holes penetrate the vascularized area and stimulate the formation of a fibrin clot containing pluripotent stem cells. This clot fills the defect and matures into fibrocartilage. Microfracture of the subchondral bone plate can be a successful procedure for generating fibrocartilage tissue and repairing damaged articular cartilage, but it still has several drawbacks. For example, if microfractures or holes are artificially created, insufficient hole depth may prevent the formation of fibrin clots; conversely, excessively deep holes may damage the subchondral bone plate, leading to adverse consequences and complications. Furthermore, while fibrocartilage formation can fill the defect, cartilage function cannot be fully restored. Another technique is the "MosaicPlasty," developed by Hungarian surgeons in 1995. This technique uses a series of dowel cutting instruments to harvest a cylindrical plug containing articular cartilage and subchondral bone from the donor site and implant it into a core hole created in the defect area. By repeating this process, a series of cylindrical grafts are transferred and arranged closely in a mosaic-like structure to create a new hyaline cartilage graft surface. This hyaline cartilage-like surface is formed, with the grafts connecting to each other through the healing response of fibrocartilage. The advantages of this technique include: the grafts are the patient's own tissue, avoiding rejection reactions associated with allogeneic or xenograft transplants; furthermore, the grafts are biphasic joint tissues, comprising both cartilage and bone, which can be implanted onto the joint surface to provide good support, while surrounding bone tissue can grow into the bone portion of the graft. However, this surgical technique is highly complex, and the grafts are taken from non-weight-bearing areas of the patient, limiting their usability. This type of transplantation may also compromise the integrity of the overall joint structure.

[0042] In some embodiments, mosaic inlay can be a regenerative method for repairing tissue defects using autologous tissue. Healthy cartilage tissue blocks are harvested from a non-weight-bearing site and directly implanted into the recipient site. In some embodiments, this procedure can be performed multiple times, the number depending on the size of the damaged area, thus the donor area can be proportional to the recipient area. In some embodiments, if the patient has a large defect, more normal tissue needs to be removed from the donor site, potentially leading to a decrease in the mechanical strength of the donor site. In some embodiments, cartilage tissue can be directly transplanted from the donor site without any treatment, and the extracellular matrix (ECM) of the cartilage is of high density. In some embodiments, the chondrocytes of the implanted cartilage may not easily migrate from the implantation site, resulting in a weaker connection between the implant and the defect and poor subchondral bone repair. Therefore, in some embodiments, the transplanted tissue may easily detach after surgery.

[0043] This disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after implantation into the cartilage of a patient; the biocompatible scaffold including a plurality of pores; and a plurality of chondrocytes embedded in the scaffold; wherein, approximately 12 months after implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 10 MPa or higher. In some embodiments, approximately 12 months after implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 12 MPa or higher. In some embodiments, approximately 12 months after implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 13 MPa or higher.

[0044] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.8 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.9 MPa or higher.

[0045] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.5 MPa or higher.

[0046] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.1 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.3 MPa or higher. In some embodiments, about 12 months after implantation of the implant into the cartilage, the implant can restore the cartilage to a state exhibiting a strain of about 0.20 to about 0.30 when subjected to a stress of about 16.4 MPa or more.

[0047] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.6 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.7 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.8 MPa or higher. In some embodiments, about 12 months after implantation of the implant into the cartilage, the implant can restore the cartilage to a state exhibiting a strain of about 0.20 to about 0.30 when subjected to a stress of about 16.9 MPa or more.

[0048] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 17.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 17.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 18.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.7 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 21.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 22.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 23.0 MPa or higher. In some embodiments, about 12 months after implantation of the implant into the cartilage, the implant can restore the cartilage to a state exhibiting a strain of about 0.20 to about 0.30 when subjected to a stress of about 25.0 MPa or more.

[0049] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 23.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa to approximately 25.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa to approximately 25.0 MPa.

[0050] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.8 MPa to approximately 24.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.0 MPa to approximately 23.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.5 MPa to approximately 22.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.0 MPa to approximately 21.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.5 MPa to approximately 20.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.7 MPa to approximately 20.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.3 MPa to approximately 25.0 MPa.

[0051] This disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after implantation into the cartilage of a patient; the biocompatible scaffold comprising a plurality of pores; a plurality of chondrocytes embedded in the scaffold; wherein, approximately 12 months after implantation into the cartilage, the implant enables the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6100 N is applied.

[0052] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6150 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6200 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6300 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6400 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6450 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6550 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7000 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7300 N is applied.

[0053] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7700 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8000 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8300 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8400 N is applied.

[0054] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8700 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 9000 N is applied.

[0055] This disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after implantation into the cartilage of a patient; the biocompatible scaffold comprising a plurality of pores; a plurality of chondrocytes embedded in the scaffold; wherein, approximately 12 months after implantation into the cartilage, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 (when subjected to a stress of approximately 10 MPa or more), and exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6100 N is applied.

[0056] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 12 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 13 MPa or higher.

[0057] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.8 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.9 MPa or higher.

[0058] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.5 MPa or higher.

[0059] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.1 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.3 MPa or higher. In some embodiments, about 12 months after implantation of the implant into the cartilage, the implant can restore the cartilage to a state exhibiting a strain of about 0.20 to about 0.30 when subjected to a stress of about 16.4 MPa or more.

[0060] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.6 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.7 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.8 MPa or higher. In some embodiments, about 12 months after implantation of the implant into the cartilage, the implant can restore the cartilage to a state exhibiting a strain of about 0.20 to about 0.30 when subjected to a stress of about 16.9 MPa or more.

[0061] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 17.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 17.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 18.0 MPa or higher.

[0062] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 19.7 MPa or higher.

[0063] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.2 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 20.5 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 21.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 22.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 25.0 MPa or higher.

[0064] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 23.0 MPa or higher. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa to approximately 25.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.0 MPa to approximately 25.0 MPa.

[0065] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 14.8 MPa to approximately 24.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.0 MPa to approximately 23.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 15.5 MPa to approximately 22.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.0 MPa to approximately 21.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.5 MPa to approximately 20.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.7 MPa to approximately 20.0 MPa. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a strain of approximately 0.20 to approximately 0.30 when subjected to a stress of approximately 16.3 MPa to approximately 25.0 MPa.

[0066] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6150 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6200 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6300 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6400 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6450 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 6550 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7000 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7300 N is applied.

[0067] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 7700 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8000 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8300 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8400 N is applied.

[0068] In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8500 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 8700 N is applied. In some embodiments, approximately 12 months after cartilage implantation, the implant allows the cartilage to recover to a state exhibiting a displacement of approximately 6 mm to approximately 9 mm when a load of approximately 9000 N is applied.

[0069] In some embodiments, the implant is inserted into an implantation hole formed in cartilage and has a longitudinal length; wherein the implantation hole has an implantation depth, wherein when the implant is inserted into the implantation hole, the implant has a first longitudinal length along the entire longitudinal length corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation hole along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least about 0.3.

[0070] In some embodiments, the implant is inserted into an implantation hole formed in cartilage and has a longitudinal length of about 10 mm or less; wherein, when the implant is inserted into the implantation hole, the implant has a first longitudinal length along the longitudinal length corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation hole along the implantation depth.

[0071] In some embodiments, the total length of the longitudinal length is about 10 mm or less. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.33. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.35. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.4. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.5. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.55. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.6. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.62. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.64. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.65. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.66. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.67. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.68. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.69. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.7. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.9. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 1.

[0072] In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 1. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.9. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.7. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.68.

[0073] In some embodiments, the ratio of the first longitudinal length to the total longitudinal length is about 0.3 to about 1. In some embodiments, the ratio is about 0.33 to about 0.95. In some embodiments, the ratio is about 0.35 to about 0.9. In some embodiments, the ratio is about 0.35 to about 0.8. In some embodiments, the ratio is about 0.37 to about 0.8. In some embodiments, the ratio is about 0.4 to about 0.8. In some embodiments, the ratio is about 0.42 to about 0.8. In some embodiments, the ratio is about 0.45 to about 0.8. In some embodiments, the ratio is about 0.45 to about 0.7. In some embodiments, the ratio is about 0.48 to about 0.8. In some embodiments, the ratio is about 0.5 to about 0.7.

[0074] In some embodiments, the implant is inserted into an implantation hole formed in the cartilage and has a total longitudinal length of about 12 mm or less. In some embodiments, the implant is inserted into an implantation hole formed in the cartilage and has a total longitudinal length of about 11 mm or less. In some embodiments, the implant is inserted into an implantation hole formed in the cartilage and has a total longitudinal length of about 10 mm or less. In some embodiments, the total longitudinal length is about 9 mm or less. In some embodiments, the total longitudinal length is about 8.5 mm or less. In some embodiments, the total longitudinal length is about 8.0 mm or less. In some embodiments, the total longitudinal length is about 7.5 mm or less. In some embodiments, the total longitudinal length is about 7.0 mm or less. In some embodiments, the total length of the longitudinal dimension is about 6.5 mm or less. In some embodiments, the total length of the longitudinal dimension is about 6.0 mm or less. In some embodiments, the total length of the longitudinal dimension is about 5.5 mm or less. In some embodiments, the total length of the longitudinal dimension is about 5.2 mm or less. In some embodiments, the total length of the longitudinal dimension is about 5.0 mm or less. In some embodiments, the total length of the longitudinal dimension is about 4.8 mm or less. In some embodiments, the total length of the longitudinal dimension is about 4.7 mm or less. In some embodiments, the total length of the longitudinal dimension is about 4.6 mm or less. In some embodiments, the total length of the longitudinal dimension is about 4.5 mm or less.

[0075] This disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after implantation into the cartilage of a patient; the biocompatible scaffold including a plurality of pores; a plurality of chondrocytes embedded in the scaffold; wherein the implant is for implantation into an implantation pore formed in the cartilage and has a longitudinal length; wherein the implantation pore has an implantation depth, wherein when the implant is implanted into the implantation pore, the implant has a first longitudinal length along its entire longitudinal length corresponding to a cartilage portion in the implantation pore along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation pore along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least about 0.3.

[0076] In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.33. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.35. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.4. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.5. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.55. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.6. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.62. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.64. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.65. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.66. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.67. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.68. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.69. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.7. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.9. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 1.

[0077] In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 1. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.9. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.7.

[0078] In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.3 to about 1. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.33 to about 0.95. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.9. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.37 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.4 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.42 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.7. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.48 to about 0.8. In some embodiments, the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.5 to about 0.7.

[0079] This disclosure relates to a transplantable implant comprising: a biocompatible scaffold that degrades over time after being implanted into the cartilage of a patient; the biocompatible scaffold including a plurality of pores; a plurality of chondrocytes embedded in the scaffold; wherein the implant is for implantation into an implantation pore formed in the cartilage and has a longitudinal length; wherein the total length of the longitudinal length is about 15 mm or less.

[0080] In some embodiments, the total length of the longitudinal length is about 14.5 mm or less. In some embodiments, the total length of the longitudinal length is about 14 mm or less. In some embodiments, the total length of the longitudinal length is about 13 mm or less. In some embodiments, the total length of the longitudinal length is about 12 mm or less. In some embodiments, the total length of the longitudinal length is about 11 mm or less. In some embodiments, the total length of the longitudinal length is about 10.5 mm or less. In some embodiments, the total length of the longitudinal length is about 10 mm or less. In some embodiments, the total length of the longitudinal length is about 9.5 mm or less. In some embodiments, the total length of the longitudinal length is about 9 mm or less. In some embodiments, the total length of the longitudinal length is about 8.5 mm or less. In some embodiments, the total length of the longitudinal length is about 8 mm or less. In some embodiments, the total length of the longitudinal length is about 7.5 mm or less. In some embodiments, the total length of the longitudinal length is about 7.0 mm or less. In some embodiments, the total length of the longitudinal length is about 6.5 mm or less. In some embodiments, the total length of the longitudinal length is about 6.0 mm or less. In some embodiments, the total length of the longitudinal length is about 5.5 mm or less. In some embodiments, the total length of the longitudinal length is about 5.2 mm or less. In some embodiments, the total length of the longitudinal length is about 5.0 mm or less. In some embodiments, the total length of the longitudinal length is about 4.8 mm or less. In some embodiments, the total length of the longitudinal length is about 4.7 mm or less. In some embodiments, the total length of the longitudinal length is about 4.6 mm or less. In some embodiments, the total length of the longitudinal length is about 4.5 mm or less. In some embodiments, the total length of the longitudinal length is about 4.3 mm or less. In some embodiments, the total length of the longitudinal length is about 4.1 mm or less. In some embodiments, the total length of the longitudinal length is about 4.0 mm or less. In some embodiments, the total length of the longitudinal dimension is about 3.9 mm or less. In some embodiments, the total length of the longitudinal dimension is about 3.8 mm or less. In some embodiments, the total length of the longitudinal dimension is about 3.7 mm or less. In some embodiments, the total length of the longitudinal dimension is about 3.6 mm or less.

[0081] In some embodiments, the biocompatible scaffold has a longitudinal length longer than a cartilage thickness. In some embodiments, the biocompatible scaffold has a longitudinal length approximately equal to or similar to the implantation depth. In some embodiments, when the biocompatible scaffold is inserted into an implantation hole having the implantation depth, the biocompatible scaffold is approximately flush with the surface of the cartilage. In some embodiments, the biocompatible scaffold is a biphasic scaffold. In some embodiments, the biocompatible scaffold includes a portion with a relatively lower porosity than another portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion with a relatively higher porosity than another portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion with a relatively lower porosity than another portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion with a relatively higher density than another portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion with a relatively higher density than another portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion having a relatively higher density than the other portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold includes a portion having a relatively lower density than the other portion of the biocompatible scaffold. In some embodiments, the biocompatible scaffold has multiple portions, each having a relatively different porosity value. In some embodiments, the biocompatible scaffold has multiple portions, each having a relatively different density value. In some embodiments, the biocompatible scaffold has multiple portions, each having a relatively different amount of polylactic-co-glycolic acid copolymer (PLGA). In some embodiments, the biocompatible scaffold has multiple portions, each having a relatively different amount of tricalcium phosphate (TCP). In some embodiments, the biocompatible scaffold has multiple portions, each having a relatively different amount of polylactic-co-glycolic acid copolymer (PLGA) and / or tricalcium phosphate (TCP).

[0082] In some embodiments, the patient is an animal. In some embodiments, the patient is a human.

[0083] In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 50%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 60%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 65%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 67%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 70%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 72%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 75%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 77%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 80%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 82%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 85%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 88%. In some embodiments, a portion of the biocompatible scaffold has a porosity of at least about 90%.

[0084] In some embodiments, the average size of the plurality of holes is approximately 100 µm to approximately 700 µm. In some embodiments, the average size of the plurality of holes is approximately 150 µm to approximately 650 µm. In some embodiments, the average size of the plurality of holes is approximately 200 µm to approximately 600 µm. In some embodiments, the average size of the plurality of holes is approximately 200 µm to approximately 550 µm. In some embodiments, the average size of the plurality of holes is approximately 200 µm to approximately 500 µm. In some embodiments, the average size of the plurality of holes is approximately 225 µm to approximately 450 µm. In some embodiments, the average size of the plurality of holes is approximately 250 µm to approximately 400 µm.

[0085] In some embodiments, the plurality of chondrocytes comprises a plurality of autologous chondrocytes.

[0086] In some embodiments, the biocompatible scaffold comprises polylactic-glycolic acid copolymer (PLGA). In some embodiments, the biocompatible scaffold comprises tricalcium phosphate (TCP).

[0087] In some embodiments, a novel method has been developed to repair articular cartilage defects using autologous cartilage proliferated in vitro. Chondrocytes are harvested from healthy articular cartilage, and the extracellular matrix is ​​digested with enzymes. The chondrocytes are proliferated in vitro for 11 to 21 days, increasing their number to more than ten times the original number. The cell concentration is then adjusted to 2.6 × 10⁻⁶. 6 Up to 5×106 The procedure involves using 100 cells / mL, with the periosteum layer sutured over the defect before injection. The problem with this technique is that during the in vitro proliferation step, chondrocytes undergo dedifferentiation, transforming from round chondrocytes into spindle-shaped fibrochondrocytes, and their biochemical properties also change. Furthermore, obtaining and suturing the autologous periosteum may not be possible under endoscopy. Additionally, this method requires at least two surgeries (one for cell harvesting and another for reimplantation), resulting in relatively high costs and limitations on the area and number of lesions that can be treated.

[0088] This disclosure relates to combining materials and cells to repair full-thickness defects of cartilage or bone. The selection of biomedical materials is based on the physical and mechanical properties of the cartilage or bone. For cartilage, naturally occurring or synthetic bioabsorbable polymers such as collagen, gelatin, alginate, polyglycolic acid, polylactic acid (PLLA), and polyglycolic acid-polylactic acid copolymer (PLGA) can be selected. For bone, biomedical ceramic materials such as hydroxyapatite, tricalcium phosphate, calcium carbonate, or calcium sulfate are selected. In some embodiments, it is also proposed to combine bioabsorbable polymers and biomedical ceramic materials to simulate the structure of bone. Regarding the cartilage structure, a porous structure is prepared to introduce surrounding tissue or serve as a scaffold for implanted cells. Furthermore, a scheme is proposed to combine chondrocytes with a gel to form a cell-containing hydrogel, which can adhere to a bone layer material to form a biphasic structure consisting of a bone layer and a cartilage layer. Since bone tissue has a stronger regenerative capacity than cartilage, the bone layer material is also designed to be porous to facilitate the introduction of surrounding bone tissue. Regarding the integration of materials and cells, a small amount of autologous cartilage tissue is harvested, digested with enzymes to remove the extracellular matrix and release chondrocytes. These chondrocytes are then implanted into a porous scaffold for proliferation. Once the proliferated chondrocytes reach an appropriate number or dosage, they are implanted into the defect site. Generally, this technique is used for simple and uniformly distributed tissues, rather than multilayered tissues. When two different cell types are implanted into a porous matrix, the cells can flow and mix because their size is smaller than the pore size of the matrix. Recent techniques for multilayer culture involve independently proliferating cartilage and bone tissue in vitro, implanting the proliferated cartilage and bone tissues into two different porous matrices, and then combining the two matrices containing cartilage and bone tissue. The boundaries between the two matrices are then fused through a re-fusion culture to form a biphasic matrix. However, this technique is time-consuming and has not yet been applied clinically.

[0089] In some embodiments, a more efficient method for tissue repair using a multilayer matrix may be provided, which may be a relatively more cost-effective approach.

[0090] Therefore, in some embodiments, a multilayer matrix and a method for tissue repair using the multilayer matrix can be provided to overcome the shortcomings of traditional articular cartilage repair techniques. In some embodiments, the multilayer matrix can be designed with a differentiated structure to allow different cells to grow in different parts of the matrix through differences in matrix structure and tissue volume. In some embodiments, the matrix containing multilayer tissue can be implanted into the defect site of a subject to repair the defect site through the tissue.

[0091] In some embodiments, a multilayer matrix is ​​provided.

[0092] In some embodiments, autologous chondrocyte transplantation (ACI) can use a biodegradable scaffold to reduce damage to natural tissue and may not require the removal of non-weight-bearing tissue. Chondrocytes or chondrogenic cells can be implanted onto the scaffold to regenerate the cartilage layer. In some embodiments, preoperative procedures and in vitro autologous chondrocyte culture may be required to obtain sufficient cells before implantation, but this requires the patient to undergo two surgeries—one for cartilage tissue harvesting and another for implantation—potentially increasing the risk of infection. In some embodiments, periosteum or perichondrium grafts may be required to fix the chondrocytes on the scaffold, a highly technical and time-consuming procedure. In some embodiments, the scaffold may be prone to displacement or dislodgement after joint activity, and the implanted chondrocyte layer, not yet recovered in the early stages, may not withstand external forces.

[0093] In some embodiments, the matrix may include a first component and a second component connected thereto, and the second component may include a hollow cavity. In some embodiments, the first component and / or the second component may be made of a composite material comprising a bioabsorbable porous material. In some embodiments, the porous material of the first component may be used to promote the growth of cells around the implantation site in the subject, and the hollow cavity of the second component may be filled with a cell block before implantation into the organism.

[0094] In some embodiments, a tissue repair method is provided that utilizes the multilayer matrix as an implant or scaffold. In some embodiments, the method may include providing the multilayer matrix, implanting a cell block into a hollow cavity of the multilayer matrix, and implanting the multilayer matrix containing the cell block into a defect site within a living organism.

[0095] In some embodiments, a multilayer implant that can be prepared according to the method described in this disclosure is provided. In some embodiments, a multilayer matrix, a tissue repair method using the multilayer matrix, and a multilayer implant prepared by the method may also be provided.

[0096] In some embodiments, the multilayer matrix of this embodiment may be a biphasic matrix that can be implanted into defects of cartilage and bone tissue. In some embodiments, the upper side of the matrix may have a hollow cavity for containing a tissue block of cells. In some embodiments, the size difference of the tissue and the porous structure of the matrix can promote controlled distribution so that chondrocytes concentrate in the upper cavity of the biphasic matrix. In some embodiments, the biphasic matrix can be implanted into a defect site in a living organism to reconstruct tissue therein.

[0097] In some embodiments, a method and carrier for in vitro culture of multilayer tissues are provided. In some embodiments, the method may include providing a porous multilayer carrier with a hollow cavity, placing a tissue block within the hollow cavity of the porous multilayer carrier, seeding cells into the carrier, and culturing the tissue block and cells within the carrier. In some embodiments, by utilizing the structure of the carrier and the volume difference between the tissue block and the cells, the tissue block and the cells can be cultured in vitro into a bilayer of cartilage tissue for multilayer tissue repair. In some embodiments, the method and carrier may be modified so that a multilayer porous matrix containing cells or tissue blocks can be directly implanted into the defect site of a organism without an in vitro culture step. In some embodiments, the multilayer porous matrix containing tissue blocks or cells can be subsequently used in a mosaic procedure. In some embodiments, a pore of similar size to the bilayer matrix can be formed at the defect site of the organism. In some embodiments, an autologous cartilage tissue block can be harvested from a non-stressed area of ​​the articular surface of cartilage. In some embodiments, to enhance the filling area, the cartilage tissue can be shredded into small pieces and digested with enzymes to release chondrocytes. In some embodiments, the partially digested tissue block can then be placed into a hollow cavity of the biphasic matrix. In some embodiments, the tissue block can be concentrated in the upper hollow cavity because the pore size of the porous structure surrounding the hollow cavity is smaller than that of the tissue block. In some embodiments, the biphasic implant containing the tissue block can then be implanted into a slot in the articular cartilage defect to regenerate tissue and repair the articular cartilage defect. In some embodiments, autologous chondrocytes can be proliferated in vitro, and the cell block or cells can be combined with a gel or other biomedical material and placed into a hollow cavity of the biphasic matrix, while the cell-containing biphasic matrix can be implanted into a slot formed at the defect site to repair a larger defect area.

[0098] In some embodiments, this tissue repair method requires only a small amount of cartilage tissue, rather than bone tissue, to be harvested as an implant, thus avoiding damage to the integrity and mechanical properties of the joint. In some embodiments, the harvested tissue block can be chopped and digested with enzymes to expand the repair area and enhance cell proliferation and fusion effects. In some embodiments, the method can be a single-step procedure performed endoscopically to reduce pain and shorten hospital stays.

[0099] In some embodiments, a multilayer matrix may be provided. In some embodiments, the matrix may include a first component and a second component connected thereto, and the second component may include a hollow cavity. In some embodiments, the first and second components may be made of a composite material comprising a bioabsorbable porous material. In some embodiments, the porous material of the first component may be used to promote the growth of cells surrounding the implantation site in an organism, and the hollow cavity of the second component may be filled with a cell mass before implantation into the organism to repair the implantation site.

[0100] In some embodiments, the composite material comprising a bioabsorbable porous material may include, but is not limited to, polylactic acid (PLA), polyglycolic acid (PGA), poly(glycolic acid-lactic acid) copolymer (PLGA), polyanhydride, polycaprolactone (PCL), polyester, polybutylene ether, collagen, gelatin, hyaluronic acid, chitin, or polyethylene glycol (PEG), with poly(glycolic acid-lactic acid) copolymer (PLGA) being preferred. In some embodiments, the pore size of the porous matrix may range from 50 to 1000 μm. In some embodiments, the composite material may further comprise other materials, including but not limited to hydroxyapatite (HAP), tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), anhydrous dicalcium phosphate (DCPA), dicalcium dihydrate phosphate (DCPD), octacalcium phosphate (OCP), or calcium pyrophosphate (CPP), with tricalcium phosphate (TCP) being preferred, or any combination thereof.

[0101] For example, in some embodiments, biodegradable polymers, such as poly(glycolic acid-lactic acid) copolymers (PLGA), can be used to prepare multilayer porous matrices. In some embodiments, the polymer can be prepared via ring-opening polymerization and can have a molecular weight range of hundreds of thousands as determined by gel permeation chromatography.

[0102] In some embodiments, PLGA may be mixed with biomedical ceramic powder (e.g., tricalcium phosphate (TCP)). In some embodiments, sodium chloride particles may be added to form pores in the matrix. In some embodiments, organic solvents such as acetone may be used to dissolve the polymer particles.

[0103] In some embodiments, the preparation of the multilayer matrix may include multiple steps, such as at least the following steps:

[0104] ● Dissolve PLGA in an organic solvent

[0105] ● Add sodium chloride granules to form a mixture

[0106] ● Pour the mixture into a mold and allow the solvent to evaporate.

[0107] ●Preparation of PLGA / TCP composite particles

[0108] ● Mix the PLGA / TCP particles with NaCl particles

[0109] ●Use filter bottles to apply negative pressure to assemble the layers of the matrix.

[0110] ●Wash away NaCl particles and residual solvent

[0111] ●The final product obtained by drying and sterilization

[0112] In some embodiments, the resulting multilayer porous matrix may have a hollow cavity at the top. The matrix can be sterilized using alcohol and phosphate-buffered saline (PBS). Material ratios, particle sizes, and processing conditions can be adjusted to achieve desired final matrix properties. For example, the ratio of PLGA to NaCl or PLGA to TCP can be varied, and particle size can be controlled by sieving. This process can prepare multilayer porous matrices suitable for a variety of biomedical applications, particularly in tissue engineering and regenerative medicine.

[0113] In some embodiments, the multilayer matrix, when used for joint defect repair, can be implanted into the joint of a living organism. In some embodiments, the cell block can be cartilage. In some embodiments, the cartilage can be harvested from the implanted organism or other organisms. In some embodiments, the cartilage tissue can be cultured in vitro. In some embodiments, the size of the cell block can be from about 100 to about 2,000 μm.

[0114] For example, in some embodiments, the prepared multilayer porous matrix has a bilayer structure, with an upper layer consisting of a hollow cavity surrounded by thick walls and a lower layer consisting of a uniform porous structure. In some embodiments, the porous structure surrounding the hollow cavity has a pore size of approximately 112 ± 41 μm and a porosity of approximately 84.2 ± 2.4 vol%. The porous structure below the hollow cavity has a pore size of approximately 115 ± 57 μm and a porosity of approximately 86.6 ± 3.1 vol%. The interface between the porous structure surrounding the hollow cavity and the porous structure below it is interconnected, without forming a closed interface. This interconnected structure allows for seamless integration between the layers of the matrix.

[0115] In some embodiments, a tissue repair method utilizing the multilayer matrix is ​​provided. In some embodiments, the method may include: providing the multilayer matrix, placing a cell block into a hollow cavity of the multilayer matrix, and implanting the multilayer matrix containing the cell block into a defect in a living organism.

[0116] In some embodiments, the cell block may be a shredded tissue block, a tissue and cell aggregate prepared by enzymatic digestion of a tissue block to release some cells, or a cell block that has proliferated in vitro and bound to a gel. In some embodiments, the enzymatic digestion time may be from about 5 minutes to about 24 hours. In some embodiments, the enzyme may include, but is not limited to, collagenase, hyaluronidase, trypsin, or protease. In some embodiments, when the defect is located on a joint, the cell block may be cartilage, and the enzyme may be collagenase.

[0117] In some embodiments, the cell mass can be a cell aggregate formed by in vitro cell culture. In some embodiments, when the implantation site is a joint defect, chondrocytes can be cultured in vitro to form the cell aggregate.

[0118] In some embodiments, the cell block may, if necessary, be a granular carrier with attached cells.

[0119] In some embodiments, the size of the cell block can be larger than the pore size of the porous material. For example, in some embodiments, the size of the cell block can be from about 100 µm to about 2,000 µm.

[0120] In some embodiments, autologous cartilage can be harvested from non-stressed areas of the joint up to the exposed subchondral bone. In some embodiments, the harvested cartilage can be shredded and filtered to achieve a size range of 560-800 μm. In some embodiments, the filtered cartilage tissue can be treated with collagenase to partially release chondrocytes.

[0121] In some embodiments, enzyme-treated cartilage tissue can be injected into a hollow cavity of a multilayer porous matrix. In some embodiments, because the tissue block size is larger than the pore size of the matrix, the tissue block can be concentrated in the upper cavity to form a biphasic matrix, wherein the upper cavity contains cartilage tissue and chondrocytes, while the lower cavity is a porous matrix.

[0122] In some embodiments, the biphasic matrix remains intact during implantation, and new cartilage tissue can be generated at the hollow cavity site. In some embodiments, a new cartilage tissue layer can form at the hollow cavity site and extend downwards to the underlying porous structure to form an interface between cartilage and bone. In some embodiments, the implanted cartilage tissue can fuse together, with no obvious interface between tissue blocks.

[0123] In some embodiments, the cartilage tissue located in the hollow cavity may secrete hyalochondral-specific substances, such as type II collagen, and will not dedifferentiate into fibrocartilage.

[0124] In some embodiments, after a period of time, the implant causes the defect to be covered with a layer of newly formed cartilage tissue, and the newly formed bone tissue extends into the implant.

[0125] In some embodiments, the biphasic implant can effectively form a new cartilage layer at the hollow cavity containing cartilage tissue. In some embodiments, the implant can effectively repair such defects, demonstrating its potential clinical applicability in cartilage repair and regeneration.

[0126] In some embodiments, the CHONDROPLUG™ implant may be a modification derived from mosaic plasty and autologous chondrocyte transplantation (ACI) methods, which allows for the removal of the extracellular matrix via enzymatic digestion on-site, processing autologous cartilage into suspended chondrocytes without the need for a second surgery. In some embodiments, enzymatic digestion can enhance chondrocyte migration and the expression of cartilage-related proteins, potentially improving cell distribution at the defect site, connectivity with surrounding tissues, and the thickness and function of the repaired cartilage. In some embodiments, the scaffold's specialized structural design allows the suspended chondrocytes to be inserted into and retained within the implant's porous and biodegradable polymer layer, thereby avoiding the need for periosteum or perichondrium transplantation, providing space for cell growth, and enhancing the mechanical strength of the cartilage layer in the early stages. In some embodiments, this biphasic biodegradable scaffold can simultaneously provide growth space for both cartilage and mineralized bone tissue, shortening the recovery period.

[0127] In some embodiments, an implant material or device (e.g., CHONDROPLUG™) may comprise various materials, such as bioresorbable polylactic-co-glycolic acid (PLGA) for chondrocyte loading and cartilage repair, and a mixture of PLGA and tricalcium phosphate (TCP) for osteoblast growth in mineralized bone. In some embodiments, an implant material or device (e.g., CHONDROPLUG™) may consist of a mixture of bioresorbable polylactic-co-glycolic acid (PLGA) for chondrocyte loading and cartilage repair, and a mixture of PLGA and tricalcium phosphate (TCP) for osteoblast growth in mineralized bone. In some embodiments, when PLGA degrades, its hydrolysis reaction can generate lactic acid and glycolic acid, creating an acidic environment at the defect site. In some embodiments, this acidic environment can induce the release of inflammatory cytokines and increase osteoblast autophagy. In some embodiments, damaged mineralized bone may be quite fragile during the first 4 to 6 weeks of the healing process and may take months to years to recover to its original mechanical strength.

[0128] In some embodiments, the surgical procedure for the CHONDROPLUG™ implant can be utilized based on different methods. For example, in some embodiments, the scaffold can be modified to reduce the amount of PLGA in the graft, thereby potentially reducing damage to mineralized bone and shortening its recovery time.

[0129] In some embodiments, to prepare the cylindrical graft, firstly, autologous full-thickness cartilage may be obtained or harvested from an animal or human. In some embodiments, chondrocytes may be isolated from the harvested cartilage using, for example, enzymes and related solutions. In some embodiments, the isolated autologous chondrocytes are injected into the cartilage phase of the CHONDROPLUG™ implant. In some embodiments, the cell-seedled implant is placed in a customized trimming device, which may include various shapes for trimming, such as a cylindrical notch and trimming blades. In some embodiments, the implant may be positioned so that the cartilage phase is within the notch while the bone phase is exposed. The exposed bone phase is cut and removed using the trimming blade. The resulting trimmed implant, consisting only of the cartilage phase, is then used as the final trimmed cylindrical graft.

[0130] In some embodiments, based on previous studies, the cartilage thickness of the knee joint is approximately 3 mm; therefore, the CHONDROPLUG™ implant can be trimmed to approximately 3.5 mm, which may comprise cartilage, subchondral bone, and a small amount of mineralized bone. In some embodiments, based on previous studies, the cartilage thickness of the knee joint is approximately 3 mm; therefore, the CHONDROPLUG™ implant can be trimmed to approximately 4.0 mm, which may comprise cartilage, subchondral bone, and a small amount of mineralized bone. In some embodiments, based on previous studies, the cartilage thickness of the knee joint is approximately 3 mm; therefore, the CHONDROPLUG™ implant can be trimmed to approximately 4.2 mm, which may comprise cartilage, subchondral bone, and a small amount of mineralized bone. In some embodiments, based on previous studies, the cartilage thickness of the knee joint is approximately 3 mm; therefore, the CHONDROPLUG™ implant can be trimmed to approximately 4.5 mm, which may comprise cartilage, subchondral bone, and a small amount of mineralized bone. In some embodiments, the CHONDROPLUG™ implant can be trimmed to approximately 5 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant can be trimmed to approximately 6 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant can be trimmed to approximately 7 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant can be trimmed to approximately 8 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant can be trimmed to approximately 9 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant may be trimmed to approximately 10 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant may be trimmed to approximately 11 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the CHONDROPLUG™ implant may be trimmed to approximately 12 mm based on the cartilage thickness of the knee joint, and may include cartilage, subchondral bone, and possibly partially mineralized bone. In some embodiments, the inclusion of subchondral bone and a small amount of mineralized bone is to prevent implant dislodgement or loosening. In some embodiments, the trimmed CHONDROPLUG™ implant is considered to combine the advantages of mosaic inlay, autologous chondrocyte transplantation (ACI), and the original CHONDROPLUG™ implant, and may eliminate potential implantation risks.In this study, we used a pig distal thigh cartilage defect model to examine the repair effect of the CHONDROPLUG™ implant after repair, and evaluated its effect through bioimaging, histology and mechanical compression tests.

[0131] Non-limiting embodiments

[0132] This disclosure is also illustrated by the following non-limiting embodiments. However, references to these or other embodiments anywhere in the specification are for illustrative purposes only and do not limit the scope or meaning of this disclosure in any way. Similarly, this disclosure is not limited to any particular preferred embodiment or aspect described herein. In fact, various modifications and variations will become apparent to those skilled in the art upon reading this specification, and such variations may be made without departing from the spirit or scope of this disclosure.

[0133] 1. A transplantable implant comprising:

[0134] A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores.

[0135] Multiple chondrocytes embedded in the scaffold;

[0136] Approximately 12 months after implantation, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14 MPa or higher.

[0137] 2. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.5 MPa or higher.

[0138] 3. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.8 MPa or higher.

[0139] 4. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.9 MPa or higher.

[0140] 5. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.0 MPa or higher.

[0141] 6. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.2 MPa or higher.

[0142] 7. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.5 MPa or higher.

[0143] 8. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.0 MPa or higher.

[0144] 9. The transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.5 MPa or higher.

[0145] 10. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 17.0 MPa or higher.

[0146] 11. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 17.5 MPa or higher.

[0147] 12. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 18.0 MPa or higher.

[0148] 13. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.0 MPa or higher.

[0149] 14. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.5 MPa or higher.

[0150] 15. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.7 MPa or higher.

[0151] 16. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.0 MPa or higher.

[0152] 17. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.2 MPa or higher.

[0153] 18. A transplantable implant as described in Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.5 MPa or higher.

[0154] 19. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 21.0 MPa or higher.

[0155] 20. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 23.0 MPa or higher.

[0156] 21. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 25.0 MPa or higher.

[0157] 22. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.0 MPa to approximately 25.0 MPa.

[0158] 23. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.8 MPa to approximately 24.0 MPa.

[0159] 24. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.0 MPa to approximately 23.0 MPa.

[0160] 25. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to exhibit a strain of approximately 0.20 to approximately 0.30 in its recovery state to a stress of approximately 15.5 MPa to approximately 22.0 MPa.

[0161] 26. The transplantable implant of Example 1, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.0 MPa to approximately 21.0 MPa.

[0162] 27. A transplantable implant comprising:

[0163] A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores.

[0164] Multiple chondrocytes embedded in the scaffold;

[0165] Approximately 12 months after implantation of the cartilage, when a load of approximately 6100 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0166] 28. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 6150 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0167] 29. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 6200 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0168] 30. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 6300 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0169] 31. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 6400 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0170] 32. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 6500 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0171] 33. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 7000 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0172] 34. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 7300 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0173] 35. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 7500 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0174] 36. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 7700 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0175] 37. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 8000 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0176] 38. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 8300 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0177] 39. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 8400 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0178] 40. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 8500 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0179] 41. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 8700 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0180] 42. The transplantable implant of Example 27, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load of approximately 9000 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0181] 43. A transplantable implant comprising:

[0182] A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores.

[0183] Multiple chondrocytes embedded in the scaffold;

[0184] Approximately 12 months after the implant was placed in the cartilage, the cartilage showed the following recovery status:

[0185] At stresses of about 14 MPa or higher, the strain is approximately 0.20 to about 0.30, and

[0186] The displacement is approximately 6 mm to approximately 9 mm when a load force of approximately 6100 N is applied.

[0187] 44. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.5 MPa or higher.

[0188] 45. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.8 MPa or higher.

[0189] 46. ​​A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.9 MPa or higher.

[0190] 47. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.0 MPa or higher.

[0191] 48. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.2 MPa or higher.

[0192] 49. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.5 MPa or higher.

[0193] 50. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.0 MPa or higher.

[0194] 51. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.5 MPa or higher.

[0195] 52. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 17.0 MPa or higher.

[0196] 53. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 17.5 MPa or higher.

[0197] 54. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 18.0 MPa or higher.

[0198] 55. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.0 MPa or higher.

[0199] 56. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.5 MPa or higher.

[0200] 57. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 19.7 MPa or higher.

[0201] 58. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.0 MPa or higher.

[0202] 59. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.2 MPa or higher.

[0203] 60. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 20.5 MPa or higher.

[0204] 61. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 21.0 MPa or higher.

[0205] 62. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 23.0 MPa or higher.

[0206] 63. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover with a strain of approximately 0.20 to approximately 0.30 at a stress of approximately 25.0 MPa or higher.

[0207] 64. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.0 MPa to approximately 25.0 MPa.

[0208] 65. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 14.8 MPa to approximately 24.0 MPa.

[0209] 66. The transplantable implant of Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.0 MPa to approximately 23.0 MPa.

[0210] 67. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 15.5 MPa to approximately 22.0 MPa.

[0211] 68. A transplantable implant as described in Example 43, wherein, approximately 12 months after implantation of the implant into the cartilage, the implant causes the cartilage to recover to a state of strain of approximately 0.20 to approximately 0.30 at a stress of approximately 16.0 MPa to approximately 21.0 MPa.

[0212] 69. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 6100 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0213] 70. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 6200 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0214] 71. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 6300 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0215] 72. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 6400 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0216] 73. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 6500 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0217] 74. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 7000 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0218] 75. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 7300 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0219] 76. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 7500 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0220] 77. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 7700 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0221] 78. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 8000 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0222] 79. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 8300 N is applied, the implant causes the cartilage to exhibit a displacement of approximately 6 mm to approximately 9 mm in its recovery state.

[0223] 80. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 8400 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0224] 81. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 8500 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0225] 82. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 8700 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0226] 83. The transplantable implant of Examples 43 to 68, wherein, approximately 12 months after implantation of the implant into the cartilage, when a load force of approximately 9000 N is applied, the implant causes the cartilage to recover with a displacement of approximately 6 mm to approximately 9 mm.

[0227] 84. A transplantable implant as described in Examples 1 to 83, wherein the implant is for implantation in an implantation hole formed in cartilage and has a longitudinal length of its entire length; wherein the implantation hole has an implantation depth; wherein, when the implant is implanted in the implantation hole, the implant has a first longitudinal length along its entire longitudinal length corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation hole along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least about 0.3.

[0228] 85. A transplantable implant as described in Example 84, wherein the total length of the longitudinal length is about 10 mm or less.

[0229] 86. A transplantable implant as described in Examples 1 to 83, wherein the implant is for implantation in an implantation hole formed in cartilage and has a longitudinal length of total length; wherein the longitudinal length of total length is about 10 mm or less; wherein, when the implant is implanted in the implantation hole, the implant has a first longitudinal length along the longitudinal length of total length corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length corresponding to a mineralized bone portion in the implantation hole along the implantation depth.

[0230] 87. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.33.

[0231] 88. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.35.

[0232] 89. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.4.

[0233] 90. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.5.

[0234] 91. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.55.

[0235] 92. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.6.

[0236] 93. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.62.

[0237] 94. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.64.

[0238] 95. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.65.

[0239] 96. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.66.

[0240] 97. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.67.

[0241] 98. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.68.

[0242] 99. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.69.

[0243] 100. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.7.

[0244] 101. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.8.

[0245] 102. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.9.

[0246] 103. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 1.

[0247] 104. The transplantable implants of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 1.

[0248] 105. The transplantable implant as described in Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.9.

[0249] 106. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.8.

[0250] 107. The transplantable implant as described in Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.7.

[0251] 108. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.68.

[0252] 109. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.3 to about 1.

[0253] 110. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.33 to about 0.95.

[0254] 111. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.9.

[0255] 112. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.8.

[0256] 113. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.37 to about 0.8.

[0257] 114. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.4 to about 0.8.

[0258] 115. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.42 to about 0.8.

[0259] 116. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.8.

[0260] 117. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.7.

[0261] 118. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.48 to about 0.8.

[0262] 119. The transplantable implant of Examples 84 to 86, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.5 to about 0.7.

[0263] 120-1. A transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 12 mm or less.

[0264] 120-2. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 11 mm or less.

[0265] 120-3. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 10 mm or less.

[0266] 120-4. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 9 mm or less.

[0267] 121. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 8.5 mm or less.

[0268] 122. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 8.0 mm or less.

[0269] 123. The transplantable implants of Examples 85 to 119, wherein the total length of the longitudinal length is about 7.5 mm or less.

[0270] 124. The transplantable implants of Examples 85 to 119, wherein the total length of the longitudinal length is about 7.0 mm or less.

[0271] 125. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 6.5 mm or less.

[0272] 126. The transplantable implants of Examples 85 to 119, wherein the total length of the longitudinal length is about 6.0 mm or less.

[0273] 127. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 5.5 mm or less.

[0274] 128. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 5.2 mm or less.

[0275] 129. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 5.0 mm or less.

[0276] 130. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 4.8 mm or less.

[0277] 131. The transplantable implant as described in Examples 85 to 119, wherein the total length of the longitudinal length is about 4.7 mm or less.

[0278] 132. The transplantable implants of Examples 85 to 119, wherein the total length of the longitudinal length is about 4.6 mm or less.

[0279] 133. The transplantable implants of Examples 85 to 119, wherein the total length of the longitudinal length is about 4.5 mm or less.

[0280] 134. A transplantable implant comprising:

[0281] A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores.

[0282] Multiple chondrocytes embedded in the scaffold;

[0283] The implant is inserted into an implantation hole formed in cartilage and has a total longitudinal length; the implantation hole has an implantation depth; when the implant is inserted into the implantation hole, the implant has a first longitudinal length along its total longitudinal length, corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length, corresponding to a mineralized bone portion in the implantation hole along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least about 0.3.

[0284] 135. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.33.

[0285] 136. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.35.

[0286] 137. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.4.

[0287] 138. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.5.

[0288] 139. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.55.

[0289] 140. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.6.

[0290] 141. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.62.

[0291] 142. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.64.

[0292] 143. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.65.

[0293] 144. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.66.

[0294] 145. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.67.

[0295] 146. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.68.

[0296] 147. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.69.

[0297] 148. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.7.

[0298] 149. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.8.

[0299] 150. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 0.9.

[0300] 151. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at least about 1.

[0301] 152. A transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 1.

[0302] 153. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.9.

[0303] 154. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.8.

[0304] 155. A transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is at most about 0.7.

[0305] 156. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.3 to about 1.

[0306] 157. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is from about 0.33 to about 0.95.

[0307] 158. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.9.

[0308] 159. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.35 to about 0.8.

[0309] 160. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.37 to about 0.8.

[0310] 161. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.4 to about 0.8.

[0311] 162. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.42 to about 0.8.

[0312] 163. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.8.

[0313] 164. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.45 to about 0.7.

[0314] 165. The transplantable implant as described in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.48 to about 0.8.

[0315] 166. The transplantable implant as in Example 1, wherein the ratio of the first longitudinal length to the total length of the longitudinal length is about 0.5 to about 0.7.

[0316] 167. A transplantable implant comprising:

[0317] A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores.

[0318] Multiple chondrocytes embedded in the scaffold;

[0319] The implant is inserted into an implantation hole formed in the cartilage and has a longitudinal length of about 10 mm or less.

[0320] 168. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 9 mm or less.

[0321] 169. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 8.5 mm or less.

[0322] 170. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 8 mm or less.

[0323] 171. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 7.5 mm or less.

[0324] 172. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 7.0 mm or less.

[0325] 173. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 6.5 mm or less.

[0326] 174. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 6.0 mm or less.

[0327] 175. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 5.5 mm or less.

[0328] 176. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 5.2 mm or less.

[0329] 177. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 5.0 mm or less.

[0330] 178. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 4.8 mm or less.

[0331] 179. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 4.7 mm or less.

[0332] 180. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 4.6 mm or less.

[0333] 181. The transplantable implant as described in Examples 1 to 167, wherein the total length of the longitudinal length is about 4.5 mm or less.

[0334] 182. The transplantable implant of Examples 1 to 181, wherein the biocompatible scaffold has a longitudinal length that is longer than a cartilage thickness.

[0335] 183. The transplantable implant as described in Examples 1 to 182, wherein the biocompatible scaffold has a longitudinal length longer than the implantation depth.

[0336] 184. The transplantable implant as described in Examples 1 to 183, wherein the patient is an animal.

[0337] 185. The transplantable implant as described in Examples 1 to 183, wherein the patient is a human being.

[0338] 186. The transplantable implants of Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 65%.

[0339] 187. The transplantable implant as described in Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 70%.

[0340] 188. The transplantable implant as described in Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 75%.

[0341] 189. The transplantable implants of Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 80%.

[0342] 190. The transplantable implants of Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 85%.

[0343] 191. The transplantable implant as described in Examples 1 to 185, wherein the biocompatible scaffold has a porosity of at least about 88%.

[0344] 192. The implantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 100 µm to about 700 µm.

[0345] 193. The transplantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 150 µm to about 650 µm.

[0346] 194. The transplantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 200 µm to about 600 µm.

[0347] 195. The implantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 200 µm to about 550 µm.

[0348] 196. The implantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is about 200 µm to about 500 µm.

[0349] 197. The transplantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 225 µm to about 450 µm.

[0350] 198. The transplantable implant as described in Examples 1 to 191, wherein the average size of the plurality of pores is from about 250 µm to about 400 µm.

[0351] 199. The transplantable implants of Examples 1 to 198, wherein the plurality of chondrocytes comprises a plurality of autologous chondrocytes.

[0352] 200. The implantable implants of Examples 1 to 199, wherein the biocompatible scaffold comprises polylactic-glycolic acid copolymer (PLGA).

[0353] 201. The transplantable implant of Examples 1 to 200, wherein the biocompatible scaffold comprises tricalcium phosphate (TCP).

[0354] Unrestricted instance

[0355] The following examples are provided to illustrate selected embodiments. They should not be considered as limiting the scope of the invention, but are merely illustrative and exemplary. Therefore, although the examples provided below are illustrated with specific medical devices or active agents, they are applicable to all types of medical devices and active agents within the scope described in this specification.

[0356] Example 1: Animal Experimentation and Surgical Procedures

[0357] This animal experiment was conducted according to the operating procedures approved by the Laboratory Animal Committee (Pig Doctor Animal Technology Co., Ltd.). Four adult Lanyu miniature pigs were used in this study. All surgeries were performed in the operating room of the veterinary hospital using standard surgical procedures and aseptic techniques. Prior to surgery, atropine, xylazine, and Zoltil 50 were administered intramuscularly as pre-anesthetic adjuvants, followed by inhaled isoflurane for induction and maintenance of general anesthesia. Surgery was performed on the right hind leg knee joint of each animal via a longitudinal incision medial to the lateral joint opening of the dislocated patella. A circular area with a diameter of 8.5 mm was marked at the center of the weight-bearing area of ​​the distal femoral condyle, and the full-thickness cartilage of this marked area was scraped away. Chondrocytes were then isolated to prepare trimmed cylindrical grafts. The preparation procedure for the trimmed cylindrical grafts loaded with autologous chondrocytes will be described later. Figure 1A In some embodiments, an implantation site is created by drilling a bone and cartilage defect with a diameter of 8.5 mm and a depth of 4.5 mm at the center of the weight-bearing portion on the surface of the distal femoral condyle. Figure 1B In some embodiments, a modified cylindrical graft was implanted into the defect and flush with the articular surface, serving as the experimental group. Figure 2A The untrimmed cylindrical graft used in the preparation method of the trimmed cylindrical graft (CHONDROPLUG™ biphasic cartilage and bone implant) shown in some embodiments. Figure 2B An example of a trimming apparatus for trimming the preparation method of a cylindrical graft, shown in some embodiments. Figure 2CShown in some embodiments, an example structure and procedure for preparing and implanting a transplantable implant, according to at least some aspects of this disclosure. (Refer to...) Figure 1A Each marked area was drilled with a defect 8.5 mm in diameter and 4.5 mm in depth. After the defect was formed, it was then... Figure 2A-2C Cylindrical grafts and devices of the type shown were used. The experimental group (animals #133 and #135, modified cylindrical grafts loaded with autologous chondrocytes) was implanted into the defect, while the control group (animals #119 and #129, empty grafts) underwent no implantation. All animals were euthanized after 12 months of care, and samples were collected for histochemical, immunohistochemical staining, and mechanical testing.

[0358] Example 2: Preparation of trimmed cylindrical grafts

[0359] The modified cylindrical grafts were obtained from implants in the "RevoCart®" single-step autologous cartilage repair system (3RC002M) from Gobo Biomedical Co., Ltd. (Taiwan). This system includes a "CHONDROPLUG™" biphasic cartilage and bone cylindrical graft, an "AccuCut®" tissue processor, enzymes, and enzyme-specific solutions. CHONDROPLUG™ is a biphasic cylindrical graft with 85% porosity, a pore size of 250-400 μm, a diameter of 8.5 mm, and a height of 8.5 mm. Figure 2A The enzyme is a mixture of type I (2.2-3.4 mg) and type II (1.5-2.3 mg) collagenase. According to the product data, the enzyme-specific solution is composed of H2O, with an osmotic pressure of 287 ± 15 mOsm / kg and a pH of 7.1-7.4.

[0360] Before obtaining the trimmed cylindrical graft, a CHONDROPLUG™ cylindrical graft loaded with autologous chondrocytes must first be prepared. In short, referring to Figure 2C, autologous full-thickness cartilage is obtained from experimental animals following the aforementioned procedure, and chondrocytes are isolated using the accompanying accessories according to the RevoCart® manual. After collecting the autologous chondrocytes, these cells are injected into the cartilage phase of the CHONDROPLUG™ using a sterile syringe, forming the final biphasic cartilage and bone cylindrical graft. Subsequently, the CHONDROPLUG™ cylindrical graft loaded with autologous chondrocytes is placed in a self-made trimming device as shown in Figure 2B. This trimming device includes at least a cylindrical groove (8.5 mm in diameter and 4.5 mm in depth) and a trimming blade. During trimming, the cartilage phase of the CHONDROPLUG™ is placed within the cylindrical groove, while the bone phase is exposed outside the groove (approximately 4 mm in height). The exposed lateral bone portion was removed using a trimming blade, and the resulting CHONDROPLUG™ cylindrical graft was considered the trimmed cylindrical graft in this study.

[0361] Example 3: Biomedical Imaging

[0362] Cartilage defects were assessed using a 128-section computed tomography (CT) scanner (Ingenuity CT, Koninklijke Philips NV) at 1, 6, and 12 months post-surgery, and were tracked using a 3.0T magnetic resonance imaging (MR) scanner (Achieva 3.0T, Koninklijke Philips NV) at 12 months post-surgery. Prior to biomedical imaging, animals were sedated with midazolam and ketamine and anesthetized with inhaled oxygen and isoflurane. Animals were placed on the CT or MR stage in a prone position with their hind limbs extended. During CT imaging, the hind limbs were scanned with a source voltage of 120 kV, an X-ray tube current of 358 mA, and a slice thickness of 1 mm. Conversely, during MR scanning, a human-compatible coil was wrapped around the right hind limb knee joint, and scans were performed using T1-weighted (T1W) and T2-weighted (T2W) sequences. Bone fraction (bone volume / total volume, BV / TV) of osteochondral defects was calculated from coronal CT images using the commercial imageJ software (with the BoneJ plugin). All measurements were derived from at least three independent calculations. Statistical significance was assessed using one-way ANOVA and post-hoc comparisons using Duncan's test. A p-value less than 0.01 was considered statistically significant.

[0363] Example 4: Histological Staining and Scoring

[0364] During euthanasia autopsies, joint specimens were collected and fixed in 10% neutral buffered formalin (NBF) for 24 to 48 hours. They were then decalcified in OSTEOSOFT® (Merck, Inc.) solution at 4°C for several weeks until further tissue trimming, graded ethanol (EtOH) dehydration, xylene treatment, paraffin embedding, and paraffin sectioning were performed. Subsequently, the sections were stained with hematoxylin-eosin (H&E), Alcian blue, Safranin O / Fast green, and Movat pentachrome, and the histological reaction and cartilage regeneration were assessed by a qualified toxicological pathologist.

[0365] The primary region of interest (ROI) focuses on the integrity of articular cartilage at the site of iatrogenic defects following implantation. Based on references published in *Arthritis Rheumatology* and *Osteoarthritis and Cartilage*, the modified scoring system used is shown in Table 1. Table 1 presents a summary of histological scores or gradings in some embodiments.

[0366] Table 1: Histological Grading

[0367]

[0368] The second region of interest (ROI) was assessed based on references published in *The Open Rheumatology Journal*, focusing on the recovery of articular cartilage stained with Safranin O and Alcian Blue, as shown in Table 2. Table 2 also shows the histological analysis of proteoglycans.

[0369] Table 2: Histological analysis of proteoglycans

[0370]

[0371] Example 5: Immunohistochemical staining and scoring

[0372] Joint tissue sections were processed in the same manner as the histological staining group. The sections were then stained with immunohistochemical (IHC) staining (anti-collagen I and anti-collagen II) for examination by a qualified toxicological pathologist to assess the immunohistochemical reaction and cartilage regeneration. A third region of interest (ROI) was selected to differentiate scar tissue (collagen I) from cartilage matrix (collagen II) by detecting the secretion of collagen I and collagen II in the regenerated tissue. Antigen reversion of rehydrated sections was performed by proteinase K digestion for 20 minutes in a humidified incubator at 37°C, followed by antibody incubation (using ab34710 as anti-collagen I and ab34712 as anti-collagen II, 10 μg / mL each, Abcam, USA), and labeled with a secondary anti-rabbit IgG antibody bound to HRP, before DAB colorimetric detection. Based on the literature published in *Osteoarthritis Cartilage*, the immunohistochemical staining results were scored using a four-stage classification method (Table 3). Table 3 shows the assessment results of collagen I and collagen II. Table 5 shows the histopathological scores of the experimental animals.

[0373] Table 3: Assessment of Collagen I and Collagen II

[0374]

[0375] Based on gross observation, histochemical and immunohistochemical staining results, a six-stage classification method (Table 4) was used to score the overall cartilage integrity, referencing the *Journal of Animal and Plant Science*. For example, Table 4 summarizes examples of classifications for articular cartilage integrity.

[0376] Table 4: Classification of Articular Cartilage Integrity

[0377]

[0378] Example 6: Mechanical Compression Test

[0379] To perform biomechanical characterization, unrestrained uniaxial tests were conducted using a computer-controlled universal testing machine (HT-2402, Hongda Instruments Co., Ltd.) to determine the compressive strength of regenerated cartilage and adjacent primary cartilage. Prior to biomechanical testing, joint specimens were fixed in 10% neutral buffered formalin (NBF) for at least 48 hours, and then trimmed into cuboids measuring 22 mm long, 20 mm wide, and 30 mm high. The trimmed specimens were then fixed in a self-made mold using an acrylonitrile-butadiene-styrene (ABS) solution to ensure stable standing. Initially, the upper loading unit of the universal testing machine was adjusted to be flush with the defect surface. The displacement speed was set to 10 mm / min, and measurement was stopped when the displacement reached 8.5 mm.

[0380] result

[0381] Biomedical Imaging and Visual Observation

[0382] Figure 3 The images shown are computed tomographic (CT) images of cartilage defects in animals at 1, 6, and 12 months post-surgery in some embodiments. Figure 4 The bone volume to total volume (BV / TV) ratio of osteochondral defects in 12-month CT images is shown in some embodiments. Figure 5 The images shown are magnetic resonance (MR) images of cartilage defects in animals 12 months after surgery in some embodiments. Figure 6A The images show the gross appearance of cartilage from euthanized animals in certain embodiments of the trimmed cylindrical graft group (animal #133). Figure 6B The images show the gross appearance of cartilage from the hollow group (animal #119) after animal euthanasia in some embodiments.

[0383] To rule out individual differences and observe changes in each defect, CT scans of the right hind limb of each animal were performed at 1, 6, and 12 months post-implantation. Figure 3 As shown. At 1 month, the modified cylindrical graft was clearly visible, showing no displacement or detachment. Over time, the modified cylindrical graft gradually shrank and became invisible, becoming completely invisible within the defect at 12 months. In the axial and sagittal sections of CT scans at 6 and 12 months post-surgery, new tissue was observed covering the defect surface at the original cartilage layer location in the modified cylindrical graft group. In contrast, because the hollow group lacked any implant support, a significant deep fissure appeared in the mineralized bone beneath the defect, failing to heal even after 12 months of postoperative care. Furthermore, no new tissue formation was observed in the defect area of ​​the hollow group. The bone volume density of the repaired defect was calculated using coronal CT images at 12 months (see [link to CT image]). Figure 4The BV / TV value of the modified cylindrical graft group (88.80±1.41) was greater than that of the empty hole group (81.45±2.45), and the difference between the two groups was statistically significant (P<0.01).

[0384] Twelve months after implantation, the animal's hind limbs were also subjected to magnetic resonance imaging (MRI) scans to further assess tissue characteristics (see [link to MRI]). Figure 5 In the T1-weighted (T1W) and T2-weighted (T2W) MRI images of the modified cylindrical graft group, brighter signals were observed around the defect area and cartilage layer, consistent with the results of computed tomography (CT) images. In the pore group, the T1W images showed a hazy appearance, while the T2W images showed a dark area within the defect; no bright signals were observed around the defect in the pore group on either T1W or T2W images. Gross cartilage appearance (see Figure 6) shows that the articular cartilage surface of the modified cylindrical graft group formed a smooth and complete covering layer. In contrast, the defect area in the pore group lacked tissue filling, and even with 12 months of postoperative care, the defect could not be completely filled and covered.

[0385] Histological staining and scoring

[0386] Figures 7A-7B The images show, in some embodiments, the results of hematoxylin and eosin (H&E) staining of articular cartilage defects in animals 12 months post-surgery, wherein... Figure 7A For the modified cylindrical graft group (animal #135), Figure 7B It belongs to the hollow-pore group (animal #129). Figure 7A and Figure 7B The scale bar is 200 µm, and the scale bar for high magnification is 50 µm.

[0387] Figures 8A-8F The following are histological staining results of articular cartilage defects in animals 12 months post-surgery in some embodiments: Figures 8A-8B Stain with Alcian Blue; Figure 8C-8D Stain with safranin O; Figure 8E-8F It is used for Mowat five-color dyeing. Among them, Figure 8A , 8C And 8E is the modified cylindrical graft group (animal #135), Figure 8B , 8D And 8F is the hollow group (animal #129). Figures 8A-8F The scale bar is 200 µm, and the scale bar for high magnification is 50 µm.

[0388] Histological evaluation of articular cartilage showed that the modified cylindrical graft group exhibited an excellent healing response, characterized by diffuse cartilage matrix accumulation and chondrocyte regeneration, accompanied by changes in cell density (see [link to original text]). Figure 7A Under high magnification, the defects showed good healing with no osteophytes or microfractures, indicating a healing state similar to normal cartilage. Conversely, the unrepaired pore group samples showed significant local cartilage loss and unhealed defects (see [reference]). Figure 7B Under high magnification, regenerated chondrocytes were observed dispersed among mineralized bone and fibrous tissue, accompanied by inflammatory reactions and invading bone fissures. However, no abnormal fragmentation such as mineralized bone hyperplasia or osteophytes was observed in the animal sections. Table 5 shows the histopathological scores of the study animals. According to the definitions in Table 1, the H&E staining results showed that the experimental group received 1 point and the control group received 11 points (see Table 5).

[0389] Table 5: Histopathological scores of the study animals

[0390]

[0391] 1: H&E staining scoring is based on Table 1;

[0392] 2: The scoring criteria for safranin O and alicin blue staining are based on Table 2;

[0393] 3: Scoring criteria for Collagen I / Collagen II are shown in Table 3;

[0394] 4: Scoring criteria for classifying articular cartilage degeneration (Table 4).

[0395] Simultaneously, the sections were stained with Alcian blue, Safranin O, and Mowatt's five-color staining method, all typical staining methods for detecting cartilage matrix strength, to further evaluate the effect of cartilage regeneration. Alcian blue can stain acidic polysaccharides (such as glycosaminoglycans) present in cartilage and other body structures, while Safranin O can be used to detect cartilage, mucin, and mast cell granules. Mowatt's five-color staining method is used to analyze the detailed process of bone healing, which can distinguish the tissue in the sections as: deep yellow dense structure, pale yellow fibrous tissue, green cartilage tissue, and red newly formed osteoid. In the modified cylindrical graft group, the cartilage matrix re-secreted by regenerated chondrocytes was functional and showed moderate to strong signal intensity in Alcian blue, Safranin O, and Mowatt's five-color staining (see Figures 8A, 8C, and 8E). The porous group showed poor cartilage regeneration and was rich in newly formed osteoid (see Figures 8B, 8D, and 8F). Because the regenerated chondrocytes had a strong signal intensity (Table 5), the group with the modified cylindrical grafts scored 7 points; while the control group scored only 1 point according to the definition in Table 2.

[0396] Immunohistochemical staining and scoring

[0397] Figures 9A-9D show immunohistochemical staining of cartilage defects in animals 12 months post-surgery in some embodiments, with Figures 9A-9B showing staining for collagen I and Figures 9C-9D showing staining for collagen II. Figures 8A and 8C show the group with trimmed cylindrical grafts (animal #135). Figures 8B and 8D show the group with open pores (animal #129). Figures 9A-9D The scale bar is 200 µm, and the scale bar under high magnification is 50 µm.

[0398] Collagen I is abundant in tendons, ligaments, dermis, and dentin, and is a major component of scar tissue formed during tissue repair. Collagen II is a major component of hyaline cartilage and a major component of articular cartilage. Therefore, in immunohistochemical staining, anti-collagen I is used to label fibrocartilage, while anti-collagen II is used to label hyaline cartilage. In the modified cylindrical graft group, the repaired cartilage showed a strong signal intensity in collagen II and a weak signal intensity in collagen I (see Figures 9A and 9C), thus scoring 2 points in collagen II (Table 5). The regenerated tissue in the control group showed only weak signal intensities in both collagen I and collagen II (see Figures 9B and 9D).

[0399] Overall, based on observations of gross appearance, histochemical staining, and immunohistochemical staining, the regenerated tissue in the open-pore group closely resembled scar tissue, and its articular cartilage belonged to category VI, characterized by maximal cell layer and matrix loss. In contrast, the matrix formed in the animals with modified cylindrical grafts consisted of functional, normal cartilage without any scar tissue. Therefore, their articular cartilage assessment belonged to category I, exhibiting characteristics of intact regenerated cartilage matrix (see Table 5).

[0400] Mechanical properties

[0401] Figure 10A The images show the gross appearance of cartilage defects in animals 12 months post-surgery before and after compression in some embodiments. Figure 10B The load-displacement curves of cartilage defects in animals 12 months post-surgery are shown in some embodiments. Figure 10C Stress-strain curves of cartilage defects in animals 12 months post-surgery are shown in some embodiments. Figures 10A-10CThe example shown is the right hind limb knee joint of animals #133 (trimmed cylindrical graft group) and #119 (hollow graft group). The cartilage layer was destroyed first upon compression compared to the mineralized bone (see example...). Figure 10A Furthermore, the samples from the hollow group showed more severe damage than those from the modified cylindrical graft group. In the modified cylindrical graft group, damaged cartilage tissue remained in the contact area between the loading unit and the defect; however, in the control group, exposed mineralized bone was clearly visible after the experiment.

[0402] In compression tests, the strength of both the experimental and control groups at 12 months post-surgery was similar to that of the native porcine femoral condyle (see example). Figure 10B and Figure 10C When the displacement was less than 6 mm, the load-displacement and stress-strain curves of each group were similar. However, when the displacement was greater than 6 mm (strain > 0.2), the maximum load and ultimate stress of the modified cylindrical graft group were better than those of the control group, and even better than those of the native porcine femoral condyle group. The elastic modulus of both the experimental and control groups was 0.156 GPa, slightly lower than that of the native porcine femoral condyle (0.170 GPa) (see Table 6).

[0403] discuss

[0404] Previous studies have shown that the PLGA and TCP biodegradable polymers in CHONDROPLUG™ implants can repair mineralized bone fissures caused by lack of scaffold support in porous structures due to weight-bearing defects. Bone marrow, rich in mineralized bone, is a source of stem cells that can provide bone marrow stem cells for osteogenic processes; TCP has good osteoconductivity, while the porous PLGA scaffold provides structural mechanical strength and space for osteoblast growth. Figure 3 As shown, no additional source of exogenous cells is required when using this implant. Therefore, the PLGA and TCP layers in the CHONDROPLUG™ implant provide an excellent scaffold for promoting mineralized bone regeneration, osteoconductivity, and osseointegration.

[0405] In addition to preventing the acidic environment from affecting cells at the defect site, knee cartilage degeneration is known to be more common in older adults. Osteoporotic and weaker surrounding muscles make it harder for mineralized bone to support the superficial cartilage, leading to accelerated wear of the cartilage on the contact and weight-bearing sides. Furthermore, because osteoblasts proliferate at a lower rate than younger osteoblasts, damaged mineralized bone takes longer to repair in older adults, and their bone regeneration and integration capabilities are also weaker. Therefore, minimizing damage to mineralized bone during implantation is crucial. This study evaluates modified CHONDROPLUG™ implants based on... Figure 3CT imaging results showed that the mineralized bone layer in the modified cylindrical graft group healed within 6 months post-implantation. While previous studies using the CHONDROPLUG™ implant also showed better healing at 6 months compared to the unmodified implant, X-rays revealed incomplete repair of the mineralized bone. This result indicates that the mineralized bone healing period for the modified CHONDROPLUG™ implant was shorter than that for the unmodified implant group, suggesting that applying this modification method to implants in patients could shorten the healing period. Since previous imaging studies indicated that the knee cartilage thickness is approximately 3 mm, the depth of the modified cylindrical graft in this study was designed to be 4.5 mm to cover the thickness of cartilage, subchondral bone, and a small amount of mineralized bone. As expected, the results showed that the modified CHONDROPLUG™, like the original CHONDROPLUG™ implant, effectively repaired the cartilage and subchondral bone, and the modified cylindrical graft did not slip or dislodge; the animals experienced no discomfort or mobility impairment after implantation. In contrast, the vacuolated group, lacking filling material, had an uneven defect surface (see Figure 6), and the calculated bone mineral density was also lower (see Figure 7). Figure 4 However, cartilage needs to remain hydrated, thick, and smooth to reduce joint friction, but the porous approach clearly cannot achieve this goal of reducing friction between the articular surface and the cartilage layer. Furthermore, the material used in the CHONDROPLUG™ implant is a DL-lactic acid / glycolic acid copolymer with a molar ratio of 85:15, which undergoes complete degradation in vitro and in vivo at 37°C in approximately 6 months. Figure 3 As shown, the implant gradually shrank during the 6-month observation period and became completely undetectable at 12 months (see example). Figure 3 and Figure 5 It should be noted that even when using the same raw materials, the actual degradation time of each implant is slightly different due to the porosity, thickness, and contact area of ​​the scaffold structure, as well as the water content and pH value around the implantation site.

[0406] At 12 months, the defect areas in both the modified cylindrical graft group and the vacuolated group showed bright shadows on CT images (see example). Figure 3 The bright shadow could be new bone, blood clots, or implants. Since CT imaging relies on X-ray injection and absorption by the object, the image intensity depends on the tissue's absorption; in other words, if two matrices have similar X-ray absorption capabilities, it's difficult to distinguish their components. Therefore, this study also used MRI to assist in determining the defect's composition. MRI images are based on the difference in the nuclear magnetic moments of hydrogen atoms in different molecules, and different sequences can distinguish the main components of the target. In the modified cylindrical graft group, a bright shadow appeared around the defect in both T1W and T2W images (see example...). Figure 5The tissue appears to be newly formed bone; conversely, the porous group shows a bright image on T1W and a dark image on T2W, suggesting that the defect area is mainly filled with adipose tissue (see example...). Figure 5 ).

[0407] Based on HE, Allicin Blue, Safranin O, and Mowatt's pentachrome staining results, the cartilage layer of the modified cylindrical graft group showed abundant chondrocyte growth, and the subchondral bone and mineralized bone layer were tightly connected without gaps (see Figures 7 and 8). In the control group, only fibrosis formed on the surface of the mineralized bone, accompanied by significant inflammation. Although chondrocytes were visible in the regenerated bone tissue, due to the lack of digestion, the cell clusters were unevenly distributed, and these chondrocytes could not form a thick and functional cartilage layer on the bone. Furthermore, due to the lack of implant, the chondrocytes in the control group could not grow correctly on the defect surface. Comparing these two groups demonstrates that the chondrocytes in the regenerated cartilage of the experimental group mainly originated from the chondrocytes obtained after digestion of the cartilage tissue, rather than from the defect site or bone marrow. This is primarily because only a small number of chondrocytes remained on the defect surface in the control group, which may have adhered during the defect fabrication process.

[0408] The primary component of native knee cartilage is hyaline cartilage, whose high water content and good elasticity provide cushioning and reduce friction. However, during regeneration of damaged cartilage, only fibrocartilage, not hyaline cartilage, is produced. Fibrocartilage is a tough, dense, and fibrous material. When hyaline cartilage tears, scar tissue forms in the original cartilage area. While scar tissue can protect the damaged area and prevent harmful bacteria from invading, it cannot provide the elasticity and function of hyaline cartilage in the knee joint. Therefore, fibrocartilage and scar tissue are not ideal knee cartilage tissue. Collagen II is the main marker of hyaline cartilage, while collagen I is the marker of fibrocartilage. Based on the immunohistochemical results in Figure 9, the modified cylindrical graft group showed high levels of collagen II and extremely low levels of collagen I, indicating that the regenerated cartilage is mainly hyaline cartilage, similar to natural knee cartilage. Two commonly used clinical repair methods—ACI and microfracture surgery—primarily produce fibrocartilage after healing, while CHONDROPLUG™ can effectively produce hyaline cartilage, thus yielding better results.

[0409] Compression test results showed that the strength of the regenerated tissue after 12 months was similar to that of the natural knee joint (see Figure 10). When the displacement was less than 6 mm, the load-displacement and stress-strain curves of each group were similar; however, when the displacement was greater than 6 mm (strain > 0.2), the maximum load and ultimate stress of the modified cylindrical graft group were better than those of the control group, and even better than those of the native porcine femoral condyle group. This is attributed to the CHONDROPLUG™ implant promoting the regeneration of a thicker and better hyaline cartilage layer (Figure 9), resulting in better absorption capacity under greater loads. It is speculated that the native porcine femoral condyle group had slightly lower maximum load and ultimate stress due to cartilage wear and lack of regeneration opportunities during the feeding process.

[0410] In some embodiments, the modified CHONDROPLUG™ implant integrates the advantages of mosaic inlay, ACI, and the original CHONDROPLUG™ implant, while reducing damage to mineralized bone and shortening the recovery period. The main component regenerated by the modified CHONDROPLUG™ implant is hyaline cartilage, which has the same cushioning and friction-reducing capabilities as natural knee cartilage.

[0411] It should be noted that the exemplary embodiments described herein are not intended to limit the scope of the invention; these embodiments are merely examples of embodiments of the invention. Any equivalent embodiments may be included within the scope of the invention. In fact, in addition to the embodiments shown and described herein, various modifications to this disclosure, such as other useful combinations of the components, will be readily apparent to those skilled in the art from the description. Such modifications and embodiments are also included within the scope of the appended claims.

Claims

1. A transplantable implant, characterized in that, Include: A biocompatible scaffold that degrades over time after being implanted into a patient's cartilage; the biocompatible scaffold contains multiple pores. Multiple chondrocytes embedded in the scaffold; The implant is inserted into an implantation hole formed in cartilage and has a total longitudinal length; the implantation hole has an implantation depth; when the implant is inserted into the implantation hole, the implant has a first longitudinal length along its total longitudinal length, corresponding to a cartilage portion in the implantation hole along the implantation depth, and optionally has a second longitudinal length, corresponding to a mineralized bone portion in the implantation hole along the implantation depth; wherein the ratio of the first longitudinal length to the total longitudinal length is at least 0.

3.

2. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is at least 0.

5.

3. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is at least 0.

6.

4. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is at most 0.

8.

5. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.3 to 1.

6. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.35 to 0.

9.

7. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.4 to 0.

8.

8. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.42 to 0.

8.

9. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.45 to 0.

8.

10. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.45 to 0.

7.

11. The transplantable implant of claim 1, characterized in that, The ratio of the first longitudinal length to the total length of the longitudinal length is 0.5 to 0.

7.

12. The transplantable implant of claim 1, characterized in that, The implant is designed to be inserted into an implantation hole formed in the cartilage and has a longitudinal length of 12 mm or less.

13. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 9.0 mm or less.

14. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 8.0 mm or less.

15. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 6.0 mm or less.

16. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 5.5 mm or less.

17. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 5.0 mm or less.

18. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 4.8 mm or less.

19. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 4.7 mm or less.

20. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 4.6 mm or less.

21. The transplantable implant of claim 12, characterized in that, The total length of this longitudinal length is 4.5 mm or less.

22. The transplantable implant of claim 1, characterized in that, The biocompatible scaffold has a longitudinal length that is longer than the thickness of the cartilage.

23. The transplantable implant of claim 1, characterized in that, The biocompatible scaffold has a porosity of at least 60%.

24. The transplantable implant of claim 1, characterized in that, The biocompatible scaffold has a porosity of at least 65%.

25. The transplantable implant of claim 1, characterized in that, The biocompatible scaffold has a porosity of at least 75%.

26. The transplantable implant of claim 1, characterized in that, The average size of these multiple holes ranges from 100 µm to 700 µm.

27. The transplantable implant of claim 1, characterized in that, The average size of these multiple holes ranges from 225 µm to 450 µm.

28. The transplantable implant of claim 1, characterized in that, These multiple chondrocytes include multiple autologous chondrocytes.

29. The transplantable implant of claim 1, characterized in that, This biocompatible scaffold contains polylactic acid-glycolic acid copolymer.

30. The transplantable implant of claim 1, characterized in that, This biocompatible scaffold contains calcium triphosphate.

Images