Self-organizing gelatin-polycaprplactone materials with good fluid transmission can promote full-thickness skin regeneration

Healing, reconstruction and recovery after skin injury have long been a major field of research, and many biomaterials have been designed for skin healing treatment. Because the skin repair process includes a series of complex processes such as hemostasis, inflammatory reactions and tissue remodeling, the microenvironment for bionic cell growth is particularly important. Herein, we used the self-organization effect of natural polymer materials to simulate the extracellular matrix, and prepared a structure-stable gelatin-polycaprplactone (Gt-PCL) through high-voltage electrospinning technology and a multiphase method. The composite material was capable of phase separation and showed a superior water retention rate and good fluid transmission effects in vivo and in vitro, which was used in repairing tests after full-thickness skin excision in rats. Gt-PCL materials showed not only good biocompatibility but also appropriate mechanical properties to effectively improve the epidermal healing rate and prevent wound expansion. RNA-sequencing and differential expression analysis showed that the polycaprolactone biomimetic formed a stable multi-stage, micro-nano composite structure with various soluble amino acids or proteins through self-organization. This material was able to repair the skin by up-regulating tissue repair-related genes, initiating neural repair and hair regeneration pathways and down-regulating the immune response and stress response-related pathways, thus avoiding secondary injury and excessive wound repair. Moreover, Itgax, a key mRNA associated with wound healing, was identified and has been shown to affect the immune and barrier profiles of the skin. Together, these results demonstrate that Gt-PCL materials promote full-thickness skin regeneration, and may have good clinical effects and potential application value in the future.