Hydrogel-Encapsulated Engineered Microbial Consortium as a Photoautotrophic "Living Material" for Promoting Skin Wound Healing.

Abstract

Genetically modified engineered microorganisms have been encapsulated in hydrogels and used as "living materials" for the treatment of skin diseases. However, their applications are often limited by the epidermal dry, nutrient-poor environment and cannot maintain functions stably for an expected sufficient time. To solve this problem, a photoautotrophic "living material" containing an engineered microbial consortium was designed and fabricated. The engineered microbial consortium comprised Synechococcus elongatus PCC7942 for producing sucrose by photosynthesis and another heterotrophic engineered bacterium (Escherichia coli or Lactococcus lactis) that can utilize sucrose for the growth and secretion of functional biomolecules. These engineered microorganisms in the "living material" were proved to function stably for a longer time than only individual microbes. Subsequently, CXCL12-secreting engineered L. lactis was used to construct the "living material", and its effect on promoting wound healing was verified in a full-thickness rat-skin defect model. The wounds treated by our hydrogel-encapsulated engineered microbial consortium (HeEMC) healed faster, with a wound area ratio of only 13.2% at day 14, compared to the remaining 62.6, 51.4, and 40.8% of the control, PEGDA, and PEGDA/CS groups, respectively. In conclusion, we established an efficient living material HeEMC to offer promising applications in the treatment of skin diseases.