Cartilage or cartilage-bone complex regeneration remains a major challenge in tissue engineering due to the intrinsic avascularity of cartilage and the limited number of functionally active chondrocytes. Inflammatory responses are known to play a crit...
Cartilage or cartilage-bone complex regeneration remains a major challenge in tissue engineering due to the intrinsic avascularity of cartilage and the limited number of functionally active chondrocytes. Inflammatory responses are known to play a critical role in regulating extracellular matrix formation and chondrogenic differentiation, yet the cellular interactions between inflammatory macrophages and chondrocytes remain poorly understood. This study aimed to investigate whether surface topography of biomaterials could modulate macrophage polarization and, in turn, promote chondrogenesis through immune-regulated pathways. Polycaprolactone membranes were fabricated with two distinct surface topographies—smooth and rough—and characterized using surface roughness profiling and water contact angle measurements. Primary chondrocytes were isolated from the articular cartilage of Sprague-Dawley rats, and RAW264.7 mouse macrophages were employed as inflammatory mediators. A transwell-based co-culture system was established for 72, 168 hours, where RAW264.7 cells were seeded on either Rs or Ss membranes and co-cultured with articular chondrocytes. Gene and protein expressions related to macrophage polarization and chondrogenic differentiation were evaluated using qPCR and Western blot analysis. The Rs group exhibited significantly higher expression of M2 macrophage markers (IL-10, CD163, and CD206) and a concurrent decrease in M1-associated markers (IL-6, iNOS, and IL-12b), compared to the Ss group. Furthermore, chondrocytes co-cultured with the Rs-conditioned macrophages demonstrated increased expression of key chondrogenic markers including SOX9, Aggrecan, and Collagen II. These findings suggest that surface roughness modulation of biomaterials can effectively induce anti-inflammatory microenvironments by promoting M2 macrophage polarization, thereby enhancing chondrogenic differentiation. In conclusion, the present study highlights the therapeutic potential of biomaterial surface engineering as an immunomodulatory strategy to support cartilage regeneration. This approach may offer a novel platform for promoting tissue integration and regeneration in temporomandibular joint cartilage-bone complex repair.