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Objectives and questions: Tissue engineering offers promising advancements in the treatment of chondral defects by employing cell-scaffold systems to regenerate cartilage. Biphasic and 3D scaffolds enhance cell migration and improve clinical outcomes, though challenges remain in achieving durable hyaline cartilage. Mesenchymal stromal cells (MSCs) are promising due to their autologous applicability, multipotency, and hypoimmunogenic properties. Combining scaffolds with pre-differentiated MSCs has proven to be advantageous. Besides BMSCs (bone marrow derived stromal cells), ASCs (adipose derived stromal cells) represent a promising cell source due to superior bioavailability, lower donor-site morbidity and ease of isolation. This study investigates controlled cartilage defect treatment using a three-dimensional, biphasic scaffold combined with autologous ASCs and BMSCs in an established porcine model.

Material and methods: This prospective, randomized preclinical study included 14 Goettingen Mini Pigs (28 knee specimens). Chondral defects (6 mm diameter, 2–3 mm depth) were surgically induced on the load-bearing medial femoral condyle of both hind limbs, preserving the subchondral plate. ASCs were obtained from the hip region and BMSCs from the iliac crest bone marrow. Cells were then isolated, cultured, characterized and stimulated to chondrogenic differentiation for 5 days before implantation. Specimens were assigned to four groups (n=7 each): Blank defects, Optimaix alone (Fa. Matricel, Aachen, Germany; scaffold of 3D collagen matrix) Optimaix scaffold seeded with ASCs and Optimaix seeded with BMSCs. After six months, specimens were analyzed for chondral repair using the O’Driscoll score, histomorphometry, and immunohistochemistry.

Results: O’Driscoll score was significantly lower in blank defects (6.5 ± 1.9) and Optimaix (9.1 ± 1.7) compared to ASCs (11.6 ± 2.7) and BMSCs (17.6 ± 1.3) treatments (p= 0.03). Histomorphometric analysis of toluidine blue staining intensity was conducted to assess differences in proteoglycan content between native cartilage and repaired tissue. Scaffold with ASCs (58% ± 11.7) and BMSCs (71.73% ± 8.6) treatments achieved a significantly higher proteoglycan content in the repaired tissue and staining positiv for Aggrecan and Col II demonstrating more advanced hyaline cartilage structure compared to blank defects (18.2% ± 3.3) and Optimaix (31.3% ± 10.2) (p < 0.02).

Discussion and conclusions: The results indicate that combining scaffolds with autologous MSCs enhances cartilage quality in porcine defect models, with BMSCs demonstrating a superior outcome. However, ASCs appear to be a competitive alternative to BMSCs. Further studies are needed to optimize ASCs application and explore their full potential as a viable cell source for cartilage regeneration.