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Review | Open Access

Microbial allies in skin trauma recovery: from immune modulation to engineered probiotic therapeutics

Aline Yen Ling Wang1 ( )Ana Elena Aviña1,2Yen-Yu Liu1Huang-Kai Kao3,4
Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan District, Taoyuan City 333, Taiwan, China
International PhD Program in Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei City 110, Taiwan, China
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan District, Taoyuan City 333, Taiwan, China
College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan District, Taoyuan City 333, Taiwan, China
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Highlights

• Engineered probiotics are emerging as active agents in wound healing, capable of modulating immuneresponses, enhancing epithelialization, and combating infections.

• This review comprehensively integrates key advances in probiotic-mediated immunomodulatory mechanisms and engineering strategies designed to enhance probiotic delivery and function in skin wound healing.

• A CXCL12-producing engineered Lactobacillus reuteri strain demonstrated accelerated wound repair in murine, minipig, and human clinical studies, and is now progressing through Phase II trials.

• A multi-cytokine-engineered Leuconostoc cremoris secreting FGF-2, IL-4, and CSF-1 accelerated wound healing in diabetic mice and achieved 83% complete closure in a Phase I DFU trial, confirming its regenerative and immunomodulatory potential.

• Smart wound healing platforms integrating engineered probiotics, responsive biomaterials, and real-time sensing technologies represent a transformative frontier in trauma care.

Abstract

Research shows that the microbiome of the skin is present as an active contributor to wound healing processes by moving past its historical infection-related function. The review investigates how commensal and probiotic bacteria affect immunomodulation while accelerating epithelial growth, together with tissue repair processes. Researchers use modern methods to link immunological concepts with material science along with synthetic biological techniques to study engineered probiotics which transform current wound treatments. The research study represents an extensive integration of recent findings concerning probiotic-mediated immunomodulatory operations and engineered approaches that improve probiotic delivery systems and their performance during skin wound healing procedures. Recent genetically engineered Lactobacillus reuteri strains that express chemokines like CXCL12 have been found to promote wound healing to an accelerated rate in animal models, and pre-clinical phases of clinical trials in the setting of diabetic foot ulcers (DFU) has demonstrated safety and therapeutic potential. Simultaneously, another live biotherapeutic product has been validated in terms of regenerative and immunomodulatory properties in animal models and in a clinical trial, a multi-cytokine-integrated strain of Lactococcus cremoris secreting FGF-2, IL-4, and CSF-1 promoted faster wound healing in diabetic mice and healed 83% of subjects in a Phase I DFU study. The range of probiotic therapies for trauma care expands due to advancements in probiotic delivery using materials and membrane vesicles derived from probiotics. This review builds a detailed framework that connects core immune functions with modern engineering methods for developing smart wound healing systems that combine engineered probiotics with bioresponsive materials and real-time monitoring systems. Engineered probiotics promise to become an alternative strategy for treating chronic wounds and infection-related complications that currently create significant medical problems.

Graphical Abstract

References

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Burns & Trauma
Article number: tkaf068

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Cite this article:
Wang AYL, Aviña AE, Liu Y-Y, et al. Microbial allies in skin trauma recovery: from immune modulation to engineered probiotic therapeutics. Burns & Trauma, 2026, 14(1): tkaf068. https://doi.org/10.1093/burnst/tkaf068

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Received: 01 May 2025
Revised: 16 September 2025
Accepted: 15 October 2025
Published: 23 October 2025
© The Author(s) 2025. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.