Macro/Microgel-Encapsulated, Biofilm-Armored Living Probiotic Platform for Regenerating Bacteria-Infected Diabetic Wounds

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Huilong Xin, Zhe Cai, Jiahui Hao, Jing An, Yi Li, Min Wen, Zhaojun Jia
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Abstract

Infectious diabetic wounds pose an arduous threat to contemporary healthcare. The combination of refractory biofilms, persistent inflammation, and retarded angiogenesis can procure non-unions and life-threatening complications, calling for advanced therapeutics potent to orchestrate anti-infective effectiveness, benign biocompatibility, pro-reparative immunomodulation, and angiogenic regeneration. Herein, embracing the emergent “living bacterial therapy” paradigm, a designer probiotic-in-hydrogel wound dressing platform is demonstrated. The platform is constructed employing a “macrogel/microgel/biofilm” hierarchical encapsulation strategy, with Lactobacillus casei as the model probiotic. Alginate gels, in both macro and micro forms, along with self-produced probiotic biofilms, served as encapsulating agents. Specifically, live probiotics are enclosed within alginate microspheres, embedded into an alginate bulk matrix, and cultivated to facilitate biofilm self-encasing. This multiscale confinement protected the probiotics and averted their inadvertent escape, while enabling sustained secretion, proper reservation, and localized delivery of therapeutically active probiotic metabolites, such as lactic acid. The resulting biosystem, as validated in vitro/ovo/vivo, elicited well-balanced antibacterial activities and biological compatibility, alongside prominent pro-healing, vasculogenic and anti-inflammatory potencies, thus accelerating the regeneration of infected full-thickness excisional wounds in diabetic mice. Such multiple encapsulation-engineered “all-in-one” probiotic delivery tactic may shed new light on the safe and efficient adoption of live bacteria for treating chronic infectious diseases.

Abstract Image

宏/微凝胶包封、生物膜装甲的糖尿病伤口再生活性益生菌平台。
糖尿病感染性伤口对当代医疗保健构成严重威胁。难治性生物膜、持续性炎症和血管生成迟缓的结合可能导致骨不连和危及生命的并发症,这就需要先进的治疗方法来协调抗感染效果、良性生物相容性、促修复性免疫调节和血管生成再生。在此,采用新兴的“活细菌治疗”范式,展示了一种设计的水凝胶益生菌伤口敷料平台。平台采用“大凝胶/微凝胶/生物膜”分层封装策略构建,以干酪乳杆菌为模型益生菌。海藻酸盐凝胶,在宏观和微观形式,连同自产的益生菌生物膜,作为封装剂。具体来说,活的益生菌被包裹在藻酸盐微球中,嵌入藻酸盐散装基质中,并培养以促进生物膜的自包裹。这种多尺度限制保护了益生菌,避免了它们的无意逃逸,同时使具有治疗活性的益生菌代谢物(如乳酸)能够持续分泌、适当保留和局部递送。由此产生的生物系统,经体外/卵内/体内验证,引发了良好的抗菌活性和生物相容性,以及突出的促愈合、血管生成和抗炎能力,从而加速了糖尿病小鼠感染的全层切除伤口的再生。这种多种包封工程的“一体化”益生菌递送策略可能为安全有效地采用活菌治疗慢性传染病提供新的思路。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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