Multifunctional Bacterial Cellulose Hydrogel Membranes with Antibacterial and Tissue-Regenerating Properties for Treatment of Infected Diabetic Wound Wasim Sajjad, Yongqiang Xiong,* Waqas Ahmad, Debabrata Dutta, Jean Felix Mukerabigwi, Muhizi Theoneste,* Teng Lu,* and Zhishen Ge* Cite This: https://doi.org/10.1021/acs.biomac.5c00841 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: Diabetic chronic wounds, particularly foot ulcers (DFU), are challenging due to sustained inflammation, bacterial infection, and dysregulated angiogenesis, disrupting healing. Current treatments lack effective multifunctional solutions. We developed bacterial cellulose (BC) hydrogel membranes embed- ding copper ion-doped, fish collagen peptide-loaded zeolite imidazole frameworks (Col-Cu@ZIFs). The biocompatible, non- toxic BC membranes provide mechanical strength and a moist wound microenvironment. Copper ions and collagen peptides are released at the wound site. Copper ions convert endogenous H 2 O 2 into antibacterial reactive oxygen species, while FCP accelerate tissue regeneration. Col-Cu@ZIF-embedded BC membranes demonstrate potent antibacterial activity and significantly promote cell proliferation and migration. In vivo studies confirm enhanced wound closure, increased collagen deposition, and stimulated neovascularization, which can be further validated through histological staining, CD31 immunohistochemistry, and up-regulated expression of regenerative and anti-inflammatory genes. Consequently, the biocompatible, multifunctional Col-Cu@ZIF-embedded BC hydrogel membranes show great potential as advanced dressings for treating infected diabetic chronic wounds. 1. INTRODUCTION Diabetes mellitus (DM) is a chronic metabolic disorder that currently affects 537 million individuals worldwide, with projections indicating an increase to 783 million by 2045. 1 Among the prevalent complications of diabetes are diabetic foot ulcers (DFUs), impacting up to 25% of the patients. 2 These ulcers frequently lead to the risk of limb removal and mortality. 3 The interrelated pathological features of diabetic wound, including sustained inflammation, bacterial infection, dysregulated angiogenesis, and microcirculatory disturbances, severely disrupt the normal wound healing trajectory, which results in chronic nonhealing lesions. Conservative medical interventions, including antibiotics, surgical debridement, negative pressure therapy, and off-loading therapy, frequently have unfavorable side effects and relatively low therapeutic efficacy. 4 Although a variety of treatment approaches have been developed for DFUs in recent years, e.g., growth factors and bioengineered skin, their effectiveness remains restricted; for a lot of DFU sufferers, there were no significant improvements. 5 Presumably, their function is single and does not fundamentally solve infection control and tissue regener- ation, leading to an unsatisfactory therapeutic efficacy. Given the complexity of diabetic wound healing, it is urgently desired to develop systems with multifunction in treating diabetic wounds, targeting to rescue infection, enhance tissue regeneration, and provide an extracellular matrix-like micro- environment. As the largest organ in the body, the skin serves as a potent barrier against pathogen invasion. 6 Inspired by the bio- functionality of the skin, it is imperative to develop skin-like versatile artificial materials with enough mechanical strength, promising anti-infection capabilities, and tissue repairing potential for chronic wound healing. 7,8 Bacterial cellulose (BC) is a carbohydrate polymer with a multilayer nanofiber 3D network structure synthesized by the bacteria (e.g., Glucona- cetobacter xylinus, Taonella mepensis, and Acetobacter xylinum), which possesses superior features including high permeability of nutrition and gas, high water contents, biocompatibility, biodegradability, excellent tensile strength and flexibility, low cost, and simple production process. 9 These advantages make BC a suitable material for artificial wound dressing fabrication since it could facilitate wound healing by providing a moist Received: May 9, 2025 Revised: July 22, 2025 Accepted: July 22, 2025 Article pubs.acs.org/Biomac © XXXX American Chemical Society A https://doi.org/10.1021/acs.biomac.5c00841 Biomacromolecules XXXX, XXX, XXX−XXX Downloaded via UNIV SCIENCE AND TECHNOLOGY CHINA on July 28, 2025 at 11:58:31 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.