Melt electrowriting (MEW)-PCL composite Three-Dimensional exosome hydrogel scaffold for wound healing

Abstract

While mesenchymal stem cell-derived exosomes hold substantial potential in wound healing, challenges persist in terms of large-scale production and activity of 2D-culture derived exosome, as well as addressing their inactivation and loss during application. 3D exosomes can be produced more efficiently and possess higher activity. However, there lacks a delivery patch mimicking nanofibrous architecture of the extracellular matrix while facilitating the in situ delivery of exosomes, thereby minimizing dissipation of exosomes and accelerating the process of wound healing. In this study, we devised a controllable GelMA hydrogel-combined Melt Electrowriting (MEW)-PCL scaffold for in situ 3D-exosome release. We showed that biocompatible scaffolds prepared by MEW have a simulated extracellular matrix with a highly controllable arrangement of nanofibers that can support cell adhesion, proliferation and differentiation. Through cell proliferation, scratch assay, and tube formation experiments, we verified that 3D exosomes could effectively stimulate cell proliferation, migration, and tube formation, with dose-dependent effects. In vivo outcomes exhibited accelerated re-epithelialization, improved collagen maturation, and enhanced angiogenesis. Our findings suggest that 3D-cultured exosomes within the scaffold significantly enhance wound repair. This innovative delivery strategy opens up new avenues for the application of MSC-derived exosomes in wound healing.