Recent investigations into micro-architecture of scaffolds has revealed that mean pore sizes are cell-type specific and influence cellular shape, differentiation, and extracellular matrix secretion. In this context, the overall goal of this study was to investigate whether scaffold mean pore sizes affect mesenchymal stem cell initial attachment, chondrogenic gene expression, and cartilage-like matrix deposition. Collagen-hyaluronic acid (CHyA) scaffolds, recently developed in our laboratory for in vitro chondrogenesis, were fabricated with three distinct mean pore sizes (94, 130, and 300 μm) by altering the freeze-drying technique used. It was evident that scaffolds with the largest mean pore sizes (300 μm) stimulated significantly higher cell proliferation, chondrogenic gene expression, cartilage-like matrix deposition, and resulting bulk compressive modulus after in vitro culture, relative to scaffolds with smaller mean pore sizes (94, 130 μm). Taken together, these findings demonstrate the importance of scaffold micro-architecture in the development of advanced tissue engineering strategies for articular cartilage defect repair.

Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual’s lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.