2. Academic Validation
  3. Natural, safety immunomodulatory derivatives of lactobacillus biofilms promote diabetic wound healing by metabolically regulating macrophage phenotype and alleviating local inflammation

Natural, safety immunomodulatory derivatives of lactobacillus biofilms promote diabetic wound healing by metabolically regulating macrophage phenotype and alleviating local inflammation

  • J Adv Res. 2025 Apr 3:S2090-1232(25)00220-6. doi: 10.1016/j.jare.2025.04.001.
Qingwei Zhou 1,  Junjie Chi 2,  Jintao Yang 3,  Xiaoyu Dong 4,  Jiali Guo 5,  Feifei Lian 5,  Abdullah Al Mamun 5,  Tianling Chen 5,  Haijuan Zhang 5,  Jiaojiao Chen 5,  Yibing Tao 4,  Yunmiao Ma 6,  Keqing Shi 7,  Jian Xiao 8
Affiliations

Affiliations

  • 1 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Medicine Department, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing 311800, China.
  • 2 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 3250035, China.
  • 3 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 3250035, China; Medicine Department, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing 311800, China.
  • 4 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 5 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 6 Medicine Department, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing 311800, China. Electronic address: sur-mym@foxmail.com.
  • 7 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 3250035, China. Electronic address: skochilly@wmu.edu.cn.
  • 8 Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: xfxj2000@126.com.
PMID: 40187726 DOI: 10.1016/j.jare.2025.04.001
Abstract

Introduction: Long-term inflammatory microenvironment further impairs the healing process of diabetic wounds. Many studies have shown that Lactobacillus can regulate immune function and promote injured tissue repair. However, the immunomodulatory function and safety of Lactobacillus biofilm (LB) on wounds need further investigation.

Objectives: In this present research, we proposed a "bacteria-free biofilm derivative therapy" and successfully extracted Lactobacillus biofilm derivatives (LBDs) by ultrasonic separation and filtration technology for the natural and safe treatment of diabetic wounds.

Methods: The study first cultured Lactobacillus anaerobically and extracted LBDs using ultrasound separation combined with filtration technology. LBDs were characterized via scanning electron microscopy, Concanavalin A fluorescence staining, and protein gel electrophoresis. In vivo diabetic wound model, wound closure rates were dynamically monitored, and tissue sections were analyzed using hematoxylin-eosin and immunofluorescence staining to evaluate LBDs' healing effects. An in vitro macrophage inflammation model was established, employing immunofluorescence, flow cytometry, and Western blotting techniques to explore the molecular mechanisms underlying LBDs' effects on macrophage phenotypes. Furthermore, whole-genome Sequencing and proteomics of LBDs-treated macrophages were performed to further elucidate the intrinsic molecular mechanisms through which LBDs regulate macrophage phenotypes.

Results: LBDs were effectively extracted utilizing ultrasonic separation coupled with filtration technology. Studies revealed that LBDs modulate the systemic metabolic reprogramming in wound-site macrophages, suppress JAK-STAT1 signaling pathway, alleviate the local inflammatory microenvironment, promote neovascularization and ultimately accelerate wound healing.

Conclusion: The LBDs retains most bioactive components of the LB. As a natural, safe and immunomodulatory agent, LBDs promote diabetic wound healing by metabolically reprogramming macrophage phenotypes and improving the local immune microenvironment, offering promising potential for regenerative applications in diabetic wound management.

Keywords

Diabetic wound healing; Immunomodulatory; Inflammation; Lactobacillus biofilm derivates; Macrophage phenotype; Metabolically.

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