Extracellular Vesicle-Based Hydrogels for Wound Healing Applications

Abstract

Hydrogels and extracellular vesicle-based therapies have been proposed as emerging therapeutic assets in wound closure. The combination of these elements has given good results in managing chronic and acute wounds. The intrinsic characteristics of the hydrogels in which the extracellular vesicles (EVs) are loaded allow for overcoming barriers, such as the sustained and controlled release of EVs and the maintenance of the pH for their conservation. In addition, EVs can be obtained from different sources and through several isolation methods. However, some barriers must be overcome to transfer this type of therapy to the clinic, for example, the production of hydrogels containing functional EVs and identifying long-term storage conditions for EVs. The aim of this review is to describe the reported EV-based hydrogel combinations, along with the obtained results, and analyze future perspectives.

Keywords: biomaterials; exosomes; extracellular vesicles; hydrogels; wound healing.

Figure 1

Wound healing process phases. 1. Hemostasis. Rupture of the veins adjacent to the wound area, infiltration of platelets and erythrocytes that begin the processes of platelet aggregation and coagulation that culminate in the fibrin clot formation. Tissue damage causes the release of mediators, such as proinflammatory cytokines, that will promote cell migration in later phases. 2. Inflammation. Infiltration of macrophages and neutrophils is enhanced by proinflammatory mediators to face infection and moderate inflammation. 3. Proliferation. Activation and migration of several cell types as keratinocytes and fibroblasts promoting angiogenesis and re-epithelization. 4. Remodeling. Fibroblasts orchestrate the ECM modulation for tissue regeneration.

Figure 2

Data analysis of EV-based biomaterials research literature. (A) Number of publications in Pub Med with “EVs AND (biomaterials or materials) AND wound healing” per year. (B) Absolute frequency diagram of biomaterials and hydrogels used in EV-based biomaterials research. (C) Absolute frequency diagram of therapeutic use of EV-based biomaterials in acute and chronic wound healing. (D) Absolute frequency diagram of EV sources.