GelMA/PEGDA microneedles patch loaded with HUVECs-derived exosomes and Tazarotene promote diabetic wound healing

Abstract

Clinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications. Graphic Abstract

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

“…The materials commonly used in the preparation of MNs include gelatin, PLGA, PVA, and chitosan. In addition to conventional drug delivery, researchers have also delivered EVs and EVMs using MNs [ 62 , 79 ]. The structural properties of the soluble shell and core of MNs facilitate the deep, slow-release, phased delivery of bioactive cargo, which synergistically promotes wound healing [ 62 ].…”

“…3 C). Also, hydrogels can be injected locally into the target organ or prepared as microneedle patches for topical application to achieve a more localized and targeted delivery of EVs [ 79 ].…”

Construction of multifunctional wound dressings with their application in chronic wound treatment

“…Chen et al developed a GelMA/PEGDA-based hydrogel MN, and the human umbilical vein endothelial cell (HUVEC)-derived exosomes and tazarotene were further encapsulated in MNs. 72 The prepared hydrogel MN could significantly accelerate collagen deposition, epithelial regeneration and angiogenesis, thereby promoting the repair of DFU.…”

Current Advances in the Development of Hydrogel-Based Wound Dressings for Diabetic Foot Ulcer Treatment

“…Ultimately, these GelMA scaffolds promoted granulation and epithelial tissue generation, as well as a favorable cell microenvironment that led to effective diabetic wound treatment [ 107 ]. More recently, Yuan and coworkers designed a novel microneedle patch system based on a GelMA/PEGDA composite matrix [ 69 ]. The rationale behind their studies was that the incorporation of gel microneedles on the inner side of the wound dressing could significantly improve transdermal delivery of target biological agents, without the pain associated with local injection approaches.…”