Micro-fragmented collagen hydrogel wound dressing: Enhanced porosity facilitates elevated stem cell survival and paracrine effects for accelerated wound maturation

Abstract

Human Adipose-derived stem cells (hADSCs), known for their mesenchymal stem cell properties, including multilineage differentiation and self-renewal, hold significant promise for chronic wound regeneration. Typically, hADSCs are utilized in cellular aggregates or hydrogels to enhance therapeutic efficacy. However, limitations such as reduced cell viability, inadequate mass transfer rates, and diminished paracrine effects hinder their clinical applications. This study explores an innovative approach by encapsulating hADSCs within a collagen/hyaluronic acid micro-fragmented collagen hydrogel wound dressing (MCWD). The resulting micro- fragmented collagen hydrogel-hADSC composite created through the integration of micro-sized hydrogel units and cells demonstrated markedly improved cell viability and activity, as well as superior therapeutic outcomes compared to conventional cell aggregates (CA) and collagen hydrogel wound dressings (CWD). In vitro assessments showed that the highly porous structure of MCWD promotes better mass transfer and enhances the viability and cytokine production of hADSCs associated with the paracrine effect. In vivo experiments further validated the effectiveness of the MCWD, revealing significant enhancements in cell proliferation, skin thickness restoration, collagen maturation, and blood vessel formation. These findings underscore the potential of MCWD as an advanced solution for wound healing applications.