Photo-crosslinkable amniotic membrane hydrogel for skin defect healing

Abstract

The human amniotic membrane (HAM) collagen matrix derived from human placenta can be decellularized (dHAM) to form a natural biocompatible material. dHAM has different bioactive substances and has been used widely in human tissue engineering research. However, dHAM has some disadvantages, e.g., poor mechanical properties, easy degradation and inconvenient operation and use, so it is not conducive to large-area or full-thickness skin defect healing. To overcome these limitations, for the first time, dHAM was grafted with methacrylic anhydride (MA) to form photocrosslinked dHAM methacrylate (dHAMMA); dHAMMA was then blended with methacrylated gelatin (GelMA), followed by the addition of a photosensitizer for photocrosslinking to obtain the fast-forming GelMA-dHAMMA composite hydrogel. Further, GelMA-dHAMMA was found to have the porous structure of a bicomponent polymer network and good physical and chemical properties. In vitro experiments, GelMA-dHAMMA was found to promote fibroblast proliferation and α-smooth muscle actin (α-SMA) expression. In vivo investigations also demonstrated that GelMA-dHAMMA promotes wound collagen deposition and angiogenesis, and accelerates tissue healing. GelMA-dHAMMA inherits the good mechanical properties of GelMA and maintains the biological activity of the amniotic membrane, promoting the reconstruction and regeneration of skin wounds. Thus, GelMA-dHAMMA can serve as a promising biomaterial in skin tissue engineering. STATEMENT OF SIGNIFICANCE: Since the early 20th century, the human amniotic membrane (HAM) has been successfully used for trauma treatment and reconstruction purposes. dHAM has different bioactive substances and has been used widely in human tissue-engineering research. In this work, the dHAM and gelatin were grafted and modified by using methacrylic anhydride (MA) to form photocrosslinked dHAMMA and methacrylated gelatin (GelMA). Then, the dHAMMA and GelMA were blended with a photosensitizer to form the GelMA-dHAMMA composite hydrogel derived from gelatin-dHAM. GelMA-dHAMMA exhibits a bicomponent-network (BCN) interpenetrating structure. dHAM dydrogel has advantages, e.g., good mechanical properties, slow degradation and convenient operation, so it is conducive to large-area or full-thickness skin defect healing.

Keywords: Bioactive substances; GelMA; Human amniotic membrane; Hydrogel; Photocrosslinking.