Accelerated healing of full-thickness skin wounds by multifunctional exosome-loaded scaffolds of alginate hydrogel/PCL nanofibers with hemostatic efficacy.

Although employing exosomes (EXOs) for promoting tissue repair is already in the pipeline as a new cell-free wound treatment, the rapid clearance of EXOs is still a challenge. This study assesses the effectiveness of a hybrid design of nanofibers and hydrogel in the controlled delivery of EXOs to wounds for an enhanced healing process. EXOs are isolated from the human placenta-derived stem cells and characterized by a novel nano-fluorescent dot blot assay. They are incorporated into an alginate hydrogel composited with a nanofibrous layer of poly(ε-caprolactone) to mimic the bilayer structure of the dermis and epidermis. The scaffold characteristics, including morphology, mechanobiological properties, physical properties, anti-inflammatory activity, and cytocompatibility are comprehensively evaluated. The tailored hydrophilic/hydrophobic design of the scaffolds presents controlled degradability, controlled EXOs release, enhanced cell proliferation, hemostatic activity with insignificant hemolysis, and a balance of strength and conformability suitable for full-thickness wound milieu. The repair of full-thickness wounds is further investigated in a rat model. Animal study results indicate that the EXO-loaded scaffolds accelerate wound closure, inflammation reduction, re-epithelialization, and collagen synthesis. For the latter, a collagen content of 22 % and 33 % higher than that for the unloaded scaffold and the control was observed, respectively.