The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n ¼ 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. 2,3 However, the original ACI procedure where a periosteal flap covers the repair area has major intrinsic limitations, such as initial mechanical weakness of the repaired site and periosteal hypertrophy. 4A wide variety of biomaterials have been introduced for cartilage repair as periosteal flap substitutes in ACI.5-8 Our research group has developed a novel biomaterial scaffold rhCo-PLA, which is a biodegradable scaffold combining recombinant human type II collagen (rhCo) and polylactide 96/4 felt (PLA). Being free of animal products, rhCo-PLA scaffold eliminates the risk of undesirable immunological responses and transmission of animal-derived pathogens.9,10 We have demonstrated the biocompatibility and neocartilage forming ability of recombinant human type II collagen.11,12 Furthermore, the recombinant technology enables batch consistency and manufacture of high purity collagen. The synthetic polylactide can be fabricated into a 3D scaffold structure that provides the repair site with mechanical support while gradually degrading as neotissue forms. However, PLAs alone have limitations in bioactivity. This is typically seen as a dense connective tissue layer around the PLA. 13 The rhCo, in contrast, is incorporated in the synthetic PLA mesh to improve its physico-chemical and biomechanical characteristics. Collagen enhances hydrophilicity of a scaffold. 6,14 Mechanical loading pumps water out of cartilage tissue, and during unloading, the water is reabsorbed. Thus, the water reabsorbing ability is an essential characteristic of a scaffold. W...

We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.

Cell therapy combined with biomaterial scaffolds is used to treat cartilage defects.We hypothesized that chondrogenic differentiation bone marrow-derived mesenchymal stem cells (BM-MSCs) in three-dimensional biomaterial scaffolds would initiate cartilaginous matrix deposition and prepare the construct for cartilage regeneration in situ. The chondrogenic capability of human BM-MSCs was first verified in a pellet culture. The BM-MSCs were then either seeded onto a composite scaffold rhCo-PLA combining polylactide and collagen type II (C2) or type III (C3), or commercial collagen type I/III membrane (CG). The BM-MSCs were either cultured in a proliferation medium or chondrogenic culture medium. Adult human chondrocytes (ACs) served as controls. After 3, 14, and 28 days, the constructs were analyzed with quantitative polymerase chain reaction and confocal microscopy and sulfated glycosaminoglycans (GAGs) were measured. The differentiated BM-MSCs entered a hypertrophic state by Day 14 of culture. The ACs showed dedifferentiation with no expression of chondrogenic genes and low amount of GAG. The CG membrane induced the highest expression levels of hypertrophic genes. The two different collagen types in composite scaffolds yielded similar results. Regardless of the biomaterial scaffold, culturing BM-MSCs in chondrogenic differentiation medium resulted in chondrocyte hypertrophy. Thus, caution for cell fate is required when designing cell-biomaterial constructs for cartilage regeneration.

Background: The International Cartilage Repair Society (ICRS) score was designed for arthroscopic use to evaluate the quality of cartilage repair. Purpose: To evaluate the reliability of the ICRS scoring system using an animal cartilage repair model. Study Design: Controlled laboratory study. Methods: A chondral defect with an area of 1.5 cm2 was made in the medial femoral condyle of 18 domestic pigs. Five weeks later, 9 pigs were treated using a novel recombinant human type III collagen/polylactide scaffold, and 9 were left to heal spontaneously. After 4 months, the pigs were sacrificed, then 3 arthroscopic surgeons evaluated the medial femoral condyles via video-recorded simulated arthroscopy using the ICRS scoring system. The surgeons repeated the evaluation twice within a 9-month period using their recorded arthroscopy. Results: The porcine cartilage repair model produced cartilage repair tissue of poor to good quality. The mean ICRS total scores for all observations were 6.6 (SD, 2.6) in arthroscopy, 5.9 (SD, 2.7) in the first reevaluation, and 6.2 (SD, 2.8) in the second reevaluation. The interrater reliability with the intraclass correlation coefficient (ICC) for the ICRS total scores (ICC, 0.46-0.60) and for each individual subscore (ICC, 0.26-0.71) showed poor to moderate reliability. The intrarater reliability with the ICC also showed poor to moderate reliability for ICRS total scores (ICC, 0.52-0.59) and for each individual subscore (ICC, 0.29-0.58). A modified Bland-Altman plot for the initial arthroscopy and for the 2 reevaluations showed an evident disagreement among the observers. Conclusion: In an animal cartilage repair model, the ICRS scoring system seems to have poor to moderate reliability. Clinical Relevance: Arthroscopic assessment of cartilage repair using the ICRS scoring method has limited reliability. We need more objective methods with acceptable reliability to evaluate cartilage repair outcomes.