Failure of articular cartilage repair / 中国组织工程研究

BACKGROUND: Articular cartilage has complex biological characteristics and high durability; therefore, natural degeneration or trauma may lead to irreversible damage of its structure and function. Repair and treatment of articular cartilage injury is an urgent problem in clinic. OBJECTIVE: To report the most common risk factors for failure of articular cartilage repair and their incidence, and to analyze the most important factors influencing the choice of specific surgical treatment for failure of cartilage repair. METHODS: The relevant articles were searched in PubMed and MEDLINE database from 2007 to 2019. The keywords were “articular cartilage, repair, clinic/clinical failure, surgery” in English. Initially, 343 articles were retrieved, and 38 articles were included for final analysis. RESULTS AND CONCLUSION: (1) Microfracture and mosaicplasty have significant failure rates in the early and middle stages after articular cartilage repair, while autologous chondrocyte implantation (ACI) and osteochondral allograft (OCA) transplantation are two effective methods for articular cartilage repair. (2) For the failure of articular cartilage repair, OCA transplantation might be a safe choice in the past. However, a higher re-failure rate of articular cartilage repair has been found in patients undergoing a failed OCA transplantation. For the patients who have failed ACI or matrix-induced ACI, further treatment with ACI or matrix-induced ACI is acceptable. In addition, patients with a history of subchondral bone marrow stimulation have a higher failure rate of ACI. (3) Treatments for cartilage repair failure depend on the type of surgical failure and area and site of cartilage defect. OCA transplantation is the most reliable method for the treatment of cartilage repair failure in subchondral bone marrow stimulation patients. ACI or matrix-induced ACI have shown acceptable therapeutic effect in patients who have suffered cartilage repair failure. When dealing with cartilage repair failure, special attention should be paid to the conditions of subchondral bone.

Similar regeneration of articular cartilage defects with autologous & allogenic chondrocytes in a rabbit model

Background & objectives: Articular cartilage defects in the knee have a very poor capacity for repair due to avascularity. Autologous chondrocyte transplantation (ACT) is an established treatment for articular cartilage defects. Animal studies have shown promising results with allogenic chondrocyte transplantation since articular cartilage is non-immunogenic. In addition to being economical, allogenic transplantation has less morbidity compared to ACT. This study was undertaken to compare ACT with allogenic chondrocyte transplantation in the treatment of experimentally created articular cartilage defects in rabbit knee joints. Methods: Cartilage was harvested from the left knee joints of six New Zealand white rabbits (R1-R6). The harvested chondrocytes were cultured to confluence and transplanted onto a 3.5 mm chondral defect in the right knees of 12 rabbits [autologous in 6 rabbits (R1-R6) and allogenic in 6 rabbits (R7-R12)]. After 12 wk, the rabbits were euthanized and histological evaluation of the right knee joints were done with hematoxylin and eosin and safranin O staining. Quality of the repair tissue was assessed by the modified Wakitani histological grading scale. Results: Both autologous and allogenic chondrocyte transplantation resulted in the regeneration of hyaline/mixed hyaline cartilage. The total histological scores between the two groups showed no significant difference. Interpretation & conclusions: Allogenic chondrocyte transplantation seems to be as effective as ACT in cartilage regeneration, with the added advantages of increased cell availability and reduced morbidity of a single surgery.

Effects of Tissue Transglutaminase on Human Chondrocytes Adhesion to Degenerated Articular Cartilage / 대한정형외과연구학회지

PURPOSE: The purpose of this study was to evaluate the effect of tissue transglutaminase(tTG) on chondrocyte adhesion to degenerated cartilage in vitro. MATERIALS AND METHODS: Human cartilage explant and chondrocytes were harvested from patients who underwent knee replacement arthroplasties for osteoarthritis. The articular cartilage surface was cut into a disc. Immunohistochemical methods was performed to detect the presence of fibronectin in articular surface. Human chondrocytes were transferred onto degenerated cartilage discs. To evaluate the effect of tTG involvement, tTG was added to the cell suspension or coated onto degenerated cartilage surface. The surface-attached cells were quantitated using the MTS assay. RESULTS: Fibronectin(FN) increased the surface of degenerated cartilage than normal cartilage. The addition of 100 and 1000 mug/ml of tTG to the cell suspension enhanced the cell adhesion to degenerated cartilages. On occasion of the involvement of 40 mug/ml of tTG, the surface coated with tTG showed an increase in the adhesion of cell as compared to the addition of tTG to the cell suspensions. CONCLUSION: The involvement of tTG to FN-exposed degenerated cartilage enhanced the chondrocyte adhesion. These findings may be applied to developing a novel tool of intraarticular injection using chondrocytes for osteoarthritis treatment.

Degree of degeneration and Chondroitinase ABC treatment of human articular cartilage affect the adhesion of transplanted chondrocyte / 대한정형외과연구학회지

PURPOSE: To determine the effect of chondrocyte degeneration on chondrocyte adhesion, cell proliferation, proteoglycan and collagen synthesis and the effect of chondroitinase ABC on them. MATERIALS AND METHOD: Human cartilage explant and chondrocytes were harvested from patients underwent knee replacement arthroplasties for osteoarthritis. The articular surface was cut into a disc. Cartilage discs were grouped by grade of degeneration; normal (G0), superficial fissure (G1), and deep fissure (G2). Human chondrocytes were transferred onto cartilage discs pretreated with Chondroitinase ABC. The number of the attached chondrocyte and the cell proliferation and the amount of secreted proteoglycan and collagen was measured. The morphology of transplanted chondrocyte and cartilage surface was assessed using scanning electron microscopy (SEM). RESULTS: The number of chondrocytes attached to G1, G2 cartilage disc is greater than that of cells attached to G0 disc. The proliferation of chondrocyte attached to G1, G2 cartilage disc is greater than that of cells attached to G0 disc. Chondroitinase ABC treatment increases chondrocyte proliferation in G0 cartilage disc, but decreases chondrocyte proliferation in G1, G2 cartilage disc. The proliferation of transplanted chondrocyte is greater in G1, G2 group than G0 group. The amount of proteoglycan and collagen synthesized by transplanted chondrocyte is greater in G1, G2 group than G0 group. Chondroitinase ABC treatment decreases proteoglycan and collagen synthesis. At 21 days after transplantation, the degenerated surface of G1 or G2 cartilage disc was covered with the matrix synthesized by the transplanted chondrocyte. The degenerated surface of cartilage disc became very similar with normal articular cartilage surface with the new matrix made by transplanted chondrocyte under SEM. CONCOUSION: In this in vitro study, the transplanted chondrocytes onto osteoarthritic cartilage could repair the defects on the surface of osteoarthritic cartilage. The transplanted chondrocyte attached, proliferated, synthesized proteoglycan and collagen better on the surface of degenerated cartilage than on that of normal cartilage, and Chondroitinase ABC treatment of cartilage surface enhanced the cell attachment and inhibited proteoglycan and collagen synthesis. These findings may be applied to developing a new method of intraarticular chondrocyte injection for the treatment of osteoarthritis.

Optical Coherence Tomography Analysis of the Rabbit Articular Cartilage after Chondrocyte Transplantation / 대한정형외과연구학회지

PURPOSE: To evaluate the ability of optical coherence tomography (OCT) to provide real-time, high-resolution structural analysis of the full thickness rabbit articular repair tissue following chondrocyte transplantation. MATERIALS AND METHODS: Full thickness articular cartilage defects were created in the patellar grooves of the distal femur of 30 adult rabbit knee joints. Allogenic cultured chondrocytes embedded in collagen gels were implanted into the surgical defects. Six animals per time point were sacrificed at 2, 4, 8, 12 and 24 weeks after surgery. The repair tissues were sequentially analyzed by arthroscopic surface imaging, OCT, and histology. RESULTS: OCT was able to identify the bone and cartilage interface in normal rabbit articular cartilage and regenerated cartilage at 24 weeks post chondrocyte implantation. OCT was able to identify fine surface fibrillations at 24 weeks. More importantly, OCT was able to detect the embedded gaps between the repair tissue and surrounding cartilage. CONCLUSION: OCT provides a minimal invasive means to obtain an instant "optical biopsy" of the rabbit articular repair tissue without damaging the specimen.

Autologous Vs Allogenic Chondrocytes Transplantation for Full Thickness Chondral Defects in Rabbit's Patella / 대한정형외과학회잡지

Biologic resurfacing of the damaged joints is an area of great interest and clinical promise because of the limited potential ofdamaged articular cartilage healing. Several methods such as spongiolization. joint dehridement and ahrasion of suhchondral hone. perichondral grafts, and osteochondral grafts have heen used to repair cartilage defects, but the results were not satisfactory. Rccently autologous chondrocyle transplantation with a pcrioslcal patch was paid an altention for its advantage , the regeneration with hyalin cartilage. But it have many disadvantages such as too expensive cost. second staged operation, and technically difficult to isolatc chondrocytes from a small volume of donor site, so we performed that a definecl cartilaee delect in the ribbit patella was treated with transplanta1ion of in virto expanded allogenic chondrocvtes and then compared with an autologous chondrocytes transplantation. Adult rabbits were used to transplant autogenously and allogenously and allogenically harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously 3x 3mmin size , extending down to the calcified zone. Chondrocytes were isolated in the femoral condyle of the opposite knee or othe rabbit knee. And then enzymatic digestion ( collagenase A and DNase I ) was performed for 5 hours room temperature in a spinner bottle and cells were seeded in a 25cm2 culture flask in Dulheccos modified essential medium (DMEM), supplemented with l0% fetal hovine serum (FBS). The culture medium was changed twice weekly. After 14 days of culture, the cells were isolated hy irypsinization and transplanted into previously made chondral defects with an autogenous periosteal patch taken from the medial aspect of tibia. Healing ol' the defects was assessed by gross examination, immunohistochemical stain, and light microscope with hematoxylin-eosin stain at 8, 16, and 24 weeks. Allogenic and autologous chondrocytes transplantation significantly increased the amount of newly tormed repair tissue compared to that found in control knees in which the Jesion was solely covered hy a periosteal patch. The repair tissue, however, had a tendency of incomplete bonding to adjacent cartilage. This study shows that allogenic and autologous articular chondrocytes that have heen expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesion. There is no signilicant diffcrence hetween allogenic and autologous chondrocytes transplantation.

Repair of Cartilage Defect by Transplantation of Cultured Chondrocyte in the Rabbit: Difference related to Size of Defect / 대한정형외과연구학회지

Chondrocytes were harvested from knee joints of immature rabbits and cultured as monolayer until confluence, then split, and grown in collgen gel. The cells were transplanted into osteochondral defect of two different sizes (Group I : 16.1mm2, Group II : 7.1mm2) made on the patellar groove of distal femur in 21 mature rabbits. Left legs were used as experimental group and right leg as control. After 7 weeks, 1 out of 5 in experimental side and none out of 5 in the control side showed cartilaginous repair in Group I and 3 out of 8 in experimental side and 2 out of 8 in control side showed cartilaginous repair in Group II. After 14 weeks, 1 out of 4 in experimental side and none out of 4 in control side showed cartilaginous repair in Group I and 2 out of 4 in experimental side and 2 out of 4 in control side showed cartilaginous repair in Group II.

Homotransplantation of Cultured Chondrocytes to prevent bony bridge formation and to help repair of the Damaged Growth Plate: An Experimental Study in a Canine tibial model / 대한정형외과학회잡지

The purpose of this study was to investigate the ability of cultured chondrocytes to prevent formation of bony bridge and possibly to repair of the damaged growth plate. Growth cartilage cells were obrained from the new born canine epiphyseal plates and was culture-expanded in high density. It took 14 days until formation of micro mass of cartilage cells which was easily removable from the culture flask. Twenty dogs were divided into two groups: group I (10), the medial side of growth plate of right proximal tibia was destroyed and cultured chondrocytes were homografted into the defect: and group II (10), the medial side of growth plate of right proximal tibia was destroyed and was left as it was. Left leg was served as a control. Serial radiological and histological observation were made until 16 weeks after homografting to determine the growth parrern. Following results were obtained. 1. In group I, 8 of 10 dogs had near normal growth with little angular deformity of the tibia, averaging 8° at post-op 16 weeks. Two dogs had 20° angulation at 16 weeks post-surgery. In contrast in group II, angular deformity was obvious at 4 weeks post-surgery, reaching 31° at 16 weeks post-surgery. 2. In group II, bony bridge was consistently formed on the medial side of the proximal tibia. In group I, the cultured chondrocytes initially appeared to be an amorphous cartiagenous mass, which, however, remained to contribute to matrix formation as time went on. 3. This study showed the ability of cultrued chondrocytes to prevent formation of bony bridge and possibly to repair the damaged growth plate. To prove the effectiveness of homografting of the growth cartilage cells for reconstruction of the growth plat, further studies should be followed.

Chondrocyte allograft transplantation for damaged growth plate reconstruction

The growth plate is responsible for longitudinal bone growth. The problem of repair of damaged growth plate in children has never been adequately solved. The purpose of this study is to investigate the ability of the cultured chondrocyte for the prevention of bony bridge and repairment of damaged growth plate. Chondrocytes were obtained from the new born canine epiphyseal plate and was cultured in high density. Fourteen days later they formed micromass easily removable from the culture flask. Twenty dogs were divided into two groups; in group I, the medial proximal tibial growth plate was destroyed and then cultured chondrocytes were transplanted into the defect, and in group II, the medial proximal tibial growth plate was left in destroyed state. Each left leg was remained as a control. The growth pattern was observed radiographically and histologically until 16 weeks after graft. 4 weeks after the operation, the angular deformity had been observed, and 31 degrees of angulation was noted at the 16th week in group II, while there was less than 8 degrees of angulation and nearly normal growth in most of dogs of group I (8 of 10 dogs). The other 2 dogs had shown 20 degrees angulation. In group II, there was definite bony bridge on the medical proximal growth plate. In group I, initially, the cultured chondrocyte remained as a amorphous cartilagenous mass, but as time progressed, amorphous cartilagenous mass had formed cartilagenous matrix which was proved by Safranin-O staining. Although this study showed the role of cultured chondrocyte as a method of preventation of bony bridge formation and possibility to repair of growth plate, further studies should be done to prove the reconstruction of the growth plate.

Cultured Chondrocyte Transplantation in the Damaged Growth Plate / 대한정형외과학회잡지

The growth plate is responsible for longitudinal bone growth and is involved in 6–15% of children's fracture. Of these injuries, 25–35% have been reported to result in some shortening or deformity, but in only 10% are the deformities sufficiently severe to lead to functional problems. The problem of repair of a demaged growth plate in children has never been adequately solved. The purpose of this study is to clarify that allograft of cultured chondrocytes can survive in the growth plate defect and can prevent the angular deformity by avoiding the formation of bone bridge. The chondrocytes were obtained from the rib cartilage of rabbit weighing 500g. The chondrocytes were cultured by socalled micromass culture method. The rabbits were divided two groups; the group I in which medial proximal tibial growth plate was destroyed, and the group II in which the cultured chondrocytes were transplanted into the right medial proximal tibial physeal defect. Each group has 10 rabbits. The tibial growth was observed grossly, radiologically and histologically until 16 weeks after graft. The angular deformity was observed from 3 weeks after operation and histologically the fusion of growth plate was observed in all of group I. In group II, there were no angular deformity and no fusion of growth plate in 7 out of 10 rabbits. Allografted cultured chondrocytes survived and produced matrix in the physeal defects. Through this study it was inferred that allograft transplantation of cultued chondrocytes in the iatrogenical physeal defect is a useful method to keep the physeal growth without cessation. However, further studies will be necessary to prove that the longitudinal growth potential resides in the transplanted chondrocytes as growth plate cartilage.