Flexible Organic Photovoltaic-Powered Hydrogel Bioelectronic Dressing With Biomimetic Electrical Stimulation for Healing Infected Diabetic Wounds

Abstract

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

Keywords: conducting hydrogel; electrical stimulation; flexible photovoltaic cells; proteomics; wound dressing.

Figure 1

a) The fabrication process of the PMH dressing involves synthesizing dopamine‐modified hyaluronic acid methacryloyl (HAMA), followed by the preparation of conductive HD‐Ag hydrogel onto a flexible MEMS electrode. The PMH dressing is obtained by connecting flexible OPV cells to the MEMS electrode, designed to provide biomimetic electrical stimulation under light conditions. The PMH dressing is then applied to a bacteria‐infected skin wound on diabetic mice. b) The illustration below outlines the ways the PMH dressing can accelerate wound healing processes among diabetics: b‐i) providing biomimetic electrical stimulation, b‐ii) inhibiting bacteria proliferation, b‐iii) accelerating reepithelization, and b‐iv) enhancing extracellular matrix organization and tissue remodeling.

Figure 2

a) The schematic of the sandwich‐structured PMH dressing, composed of large‐area flexible OPV cells on the top, a flexible MEMS electrode in the middle, and a hydrogel in contact with skin at the bottom. b) Stress finite element analysis of the MEMS electrode. c) Finite element simulation of mechanical properties for organic semiconductor materials. d) J–V curves of binary and ternary OPV cells. e) The J–V features of the OPV cells with different areas. f) The external quantum efficiency (EQE) spectra of the OPV cells.

Figure 3

Studies of the physical properties, cytocompatibility, and antibacterial activity of the HD‐Ag hydrogels. a) The release profile of Ag⁺ ions, b) swelling ratio, and c) electrical conductivity of the HD‐Ag hydrogels. d) Representative live/dead stain images of fibroblasts and keratinocytes co‐cultured with the hydrogels for 3 days; green represents live cells, while red represents dead cells. Cells cultured on a tissue culture plate (TCP) were used as control. e,i) Representative photographs and quantification analysis of the inhibition zone against MRSA or PAO bacteria by different hydrogel disks. f) Quantitative analysis of the MRSA and PAO colonies incubated with each hydrogel for 24 h. The initial number for two bacterial types was 5 × 10⁷ in this experiment. g,h) Cell proliferation analysis of fibroblasts and keratinocytes co‐cultured with the HD‐Ag hydrogels for 1, 3 and 5 days. The data were presented as mean ± SD (n = 3, *p < 0.05).

Figure 4

PMH dressing enhanced bacteria‐infected diabetic wound healing in vivo. a) Timeline of model establishment, dressing treatment, wound observation, and tissue harvest in the animal experiment. b) Representative images of the wound at predetermined time points. c) Wound healing boundaries overlayed on each image. d) HE and e) Masson staining of tissue sections from the wounded areas and adjacent skin. f) Analysis of wound closure. g) Analysis of re‐epithelization percentage. h) Analysis of collagen content. Data were shown as mean ± SD (n = 3, *p < 0.05 when compared with Blank group; #p < 0.05 when compared with PM patch group; and &p < 0.05 when compared with HD‐Ag₂ group).

Figure 5

a) Schematic diagram of tissue collection and proteomics analysis. b) The expression levels of identified co‐expressed proteins are illustrated in a heatmap. c) PCA results. d) DEPs are presented in a volcano plot. e) Venn diagram comparing DEPs to an extracellular matrix proteomics dataset. f) Results of the gene ontology (GO) analysis for the upregulated proteins. g) Results of the GO analysis for the downregulated proteins. h) Functional analysis (KEGG and Reactome analysis) results of the upregulated proteins. i) Functional analysis results of the downregulated proteins.

Figure 6

Pathway analysis of the a) highly expressed DEPs and b) low expressed DEPs correlated with extracellular matrix reveals significant enrichment of proteins involved in collagen organization and metallopeptidase activity. GeneMANIA (https://genemania.org/) was used for the analysis. c) Immunofluorescence observation of collagen‐I (Col‐I) and CD31 staining. The immunofluorescence intensity of positive d) Col‐I and e) CD31 cells present at the wound beds in each group was compared to that of the blank group, which was set as 100%, with other groups calculated as a percentage. Data were shown as mean ± SD (n = 3, *p < 0.05 when compared with Blank group; #p < 0.05 when compared with PM patch group; and &p < 0.05 when compared with HD‐Ag₂ group).