Probing the role of scaffold dimensionality and media composition on matrix production and phenotype of fibroblasts

• Fibroblasts encapsulated in 3D collagen gel provide a better template towards generation of dermal equivalent.
• High glucose media induced spindle like morphology of fibroblasts and enhanced collagen production compared to other media.
• 3D culture conditions affect the overall microenvironment of the cell.

Porous sponges, hydrogels, and micro/nanofibrous matrix are most commonly used three dimensional (3D) biomaterials in tissue engineering; however, reciprocal interaction between internal dimensionality of biomaterials and fibroblasts remains largely unexplored. Such studies would have potential to generate valuable insights about wound healing, tissue morphogenesis and homeostasis. To the best of our knowledge this is the first study to evaluate functionality of porous collagen matrix and collagen gels for in vitro culture of fibroblasts while investigating the role of culture media composition in modulating morphology, phenotype, extracellular matrix (ECM)-related gene expression and protein synthesis by fibroblasts. Encapsulation of fibroblasts in collagen gel was found to be more effective for ECM production compared to scaffold-based culture, as evidenced by enhanced collagen type I, elastin, lysyl oxidase, aggrecan gene expression. High glucose media induced spindle like morphology of typical in vivo fibroblasts and enhanced collagen production compared to other media. This variation in biosynthesis in different glucose concentrations was possibly due to endogenous activation of TGF-β or by an increase in ATP consuming anabolic pathways in high glucose concentration.

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