Super Absorbent Decellularized Human Amniotic Membrane Microgel for Chronic Wound Healing and Accelerated Skin Regeneration

Abstract

Chronic wounds present a persistent clinical challenge, often requiring grafts for effective healing. Rich extracellular matrix (ECM) components, cytokines, and growth factors in human amniotic membrane, has demonstrated significant potential in promoting chronic wound healing. However, decellularized human amniotic membrane sheets or hydrogels face challenges in application flexibility and cell infiltration in chronic wound healing. In this study, we developed a novel super absorbent microgel derived from decellularized human amniotic membrane, designed as a biocompatible and injectable alternative to conventional autografts.The human amniotic membrane was successfully decellularized to prevent immune rejection, verified through histological staining and DNA quantification. The ECM components derived from digesting decellularized human amniotic membrane were functionalized and incorporated into a hydrophilic polymer network composed of sodium alginate and carboxymethyl cellulose, forming a stable 3D gel structure via ionic crosslinking. Subsequent lyophilization and ball milling produced a dry microgel powder with enhanced storage and handling capabilities. The optimized formulation exhibited excellent swelling, water retention, and degradation properties. In vitro studies confirmed the microgel's biocompatibility and strong skin adhesion during dynamic movement. The injectable suspension enabled conformal coverage of deep and irregular wounds. In vivo application on diabetic mice demonstrated accelerated reepithelialization, reduced inflammation, and improved tissue remodeling. Compared to SkinColofibre, the experimental microgel (dESCM) significantly shortened the inflammatory phase and promoted faster wound closure. This study highlights the potential of ECM incorporated micronized hydrogel networks as a transformative solution in regenerative medicine for chronic wound healing and skin regeneration.