Spatiotemporal variations of contact stress between liquid-crystal films and fibroblasts Guide cell fate and skin regeneration

The inductions of both the mechanical microenvironment on cell behaviour and the polymeric scaffold on tissue regeneration have been well-proved. This study is aimed to investigate the possibility of guiding cell fate and tissue regeneration by the spatiotemporal controlling of contact stress between matrix materials and cells and to elucidate the mechanisms underlying. A series liquid crystal polymers of cholesteryl-oligo(lactic acid) (CLA) and an amorphous polymer of poly(lactic acid) were used as the growth substrates for fibroblast and skin tissue regeneration. The cellular and animal experiments show that, in the initial stage of wound healing, the liquid crystal texture of CLA films can provide an induced stress for the formation of focal adhesions and the activation of integrin beta 1/AKT signal pathway, resulting in advanced phenotypic transformation of fibroblasts to myofibroblasts, promoted collagen secretion and fast wound filling. But the gradually weakening cellular contact stress, induced by the decreasing of liquid crystal domains of matrix polymer during degradation, triggers the apoptosis of fibroblasts and myofibroblasts, resulting in non-excessive collagen accumulation. Finally, the CLA groups exhibit no obvious scar formation, more regular cell arrangement and significantly lower type I collagen proportion in regenerated tissue than other groups. This study may inspire a new, effective and safe strategy for tissue regeneration.