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

## TL;DR

This paper explores how engineered probiotics, like Lactobacillus reuteri and Lactococcus cremoris, can speed up wound healing by modulating the immune system and promoting tissue repair.

## Contribution

The paper introduces engineered probiotics that secrete multiple therapeutic proteins, showing promise in accelerating wound healing in diabetic models.

## Key findings

- Genetically modified Lactobacillus reuteri expressing CXCL12 accelerates wound healing in animal models.
- A multi-cytokine strain of Lactococcus cremoris healed 83% of diabetic foot ulcer subjects in a Phase I trial.
- Engineered probiotics combined with bioresponsive materials offer a new approach for chronic wound treatment.

## 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