From stimuli-responsive polymers to nanosystems and electrocircuits: An update on the current state of polymeric hydrogel microneedles for wound healing

Current wound treatments often lack therapeutic efficacy, which in severe cases might lead to permanent comorbidities, and even compromise the patient’s life. Additionally, several drug molecules often pose substantial challenges, having low solubility and/or permeation, or reduced stability, and frequently conventional topical and transdermal formulations lead to reduced therapeutic outcomes, substantial side-effects, and low patient compliance. To tackle these issues, polymeric hydrogel microneedles have emerged. This review offers a critical update on the current state of polymeric hydrogel microneedles for wound healing purposes, developed for diabetic wound treatment, infected wound treatment, scarring prevention, kelloid scar treatment, or general wound regeneration purposes. Bioderived and synthetic functional polymers, such as chitosan, gelatin and gelatin methacryloyl, hyaluronic acid and methacrylated hyaluronic acid, poloxamer® 407, polyacrylamide, polycaprolactone, polydopamine, polyethylene glycol diacrylate, poly(γ-glutamic acid), polylysine, poly(N-isopropylacrylamide), polyurethane, polyvinyl alcohol, polyvinylpyrrolidone, and silk fibroin have led to microneedle patches with good biocompatibility, suitable mechanical properties, controlled drug release, and overall high bioavailabiltiy, delivering to wound tissues bioactive entities such as metals and metal MOFs (magnesium, silver, iron, zinc), growth factors (VEGF, hEGF), exosomes (mesenchymal stem cell-derived, M2 macrophage-derived), other synthetic or endogenous molecules (adenosine, S-nitrosoglutathione, tazarotene, graphene oxide, mupirocin, insulin, CaO 2 , metformin), plants or algae ( Chlorella vulgaris , Centella asiatica ), or plant-derived molecules (gallic acid, tanic acid, asiaticoside, Panax notoginseng saponins, carvacrol, quercetin). Complex and multifunctional systems are described, including nanometric platforms and patches containing electrocircuits, showing high efficacy in accelerating wound healing, with multiple synergistic effects, giving origin to novel relevant therapeutic platforms.