Umbilical Cord Mesenchymal Stem Cells Delivery Onto Biological Scaffold Improves Cutaneous Wound Healing

The skin consists of epidermis,dermis,and subcutaneous tissue,forming the first barrier to protect the body.As well as acting as an external barrier to the body,the skin is also the most vulnerable organ.Loss of normal barrier and thermoregulatory functions of skin,especially disruption of tissue or cellular integrity can have devastating consequences in patients with burns,trauma and chronic wounds.The large burns or trauma lack temporary extracellular matrix making them difficult to heal.In cases of extensive skin loss,tissue engineering is essential.Currently,the main clinical strategy is skin substitutes transplant.However,skin substitutes which constituted of both the epidermal and the dermal layers remain serious limitations and challenges,such as in vivo viability of autologous keratinocytes and fibroblasts and survival and functionality of these grafts on wound beds after transplant.To mimicking the extracellular matrix in the dermal tissues,in this study,we mixed self-collected type I collagen with chondroitin sulfate as raw materials,and prepared porous scaffolds by freeze-drying.Regenerative medicine has considerable potential value to the healing of large skin injuries.Umbilical cord-derived mesenchymal stem cells(UCMSCs)have potential for selfrenewal and potential for multilineage differentiation into adipocytes,osteoblasts and smooth muscle cells.They are one of the most ideal cells on regenerative medicine and tissue engineering.In this study,primary cultured UCMSCs were inoculated into the prepared scaffold and incubated for 7 days after morphological and phenotypic identification.Immunofluorescence showing that it is biocompatible with UCMSCs.To investigate the effect on wound healing,we transplanted full-thickness skin wound murine models with scaffolds loaded with UCMSCs.PBS sham treatment,single cell suspension treatment and single scaffold treatment were used as controls.H&E and immunofluorescence staining shown UC/SC treatment had improved re-epithelialization.Immunofluorescence of CD31 and α-SMA shown UC/SC treatment had increased capillary formation and vessel maturation.To explore the expression levels of factors related to healing and inflammatory response during wound repair,we detected the relative m RNA expression levels of chemokines CXCR4 and TGFβ1,as well as inflammatory factors IL1β,IL10,IL6 and IL4.The results shown UCMSCs-laden scaffold promoted the migration of UCMSCs and improved the expression of anti-inflammatory factors.This study provides a potential therapeutic strategy for the clinical treatment of skin wounds.