Could open the door to new bioactive healing strategies
External wounds such as skin cuts or abrasions can often be easily covered with a simple Band-Aid or a larger wound patch to protect them and facilitate their healing. When it comes to some internal surfaces like those of the gut that are coated with a mucus layer, however, such conventional wound healing materials are ineffective because the mucus hinders their firm attachment and quickly carries them away from the wound site.
Now, researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a solution to this problem in the form of probiotic hydrogels made from mucoadhesive nanofibers and produced by an engineered natural gut bacterium. The hydrogels can be easily produced from bacterial cultures and applied as longer-lived self-regenerating “live gels” or shorter-lived “cell-free gels” to intestinal surfaces via syringes, spray, and endoscopic techniques to provide a seal. The study is published in Advanced Materials.
“This new type of engineered living material with its ease of production and storability, biocompatibility, and mucoadhesive properties could be a door-opener for bioactive wound healing strategies for use inside the human gut lumen,” said Neel Joshi, who is a core faculty member at the Wyss Institute and associate professor at SEAS. “We can essentially program the normal nanofiber-producing molecular machinery of nonpathogenic E. coli to produce hydrogels that have a viscosity strongly resembling that of mucus, and with mucoadhesive capabilities built into them; and their modularity could allow us to tune them to match specific sections of the gastrointestinal tract with their individual mucus compositions and structures.”
Joshi’s and other laboratories have previously harnessed commensal strains of E. coli to secrete biofilm-forming nanofibers, and as living foundries for the fabrication of pharmaceuticals, fine chemicals, or substances that can help with environmental remediation by engineering the CsgA protein that the bacteria secrete, which self-assembles into curli nanofibers in the extracellular environment. In these past applications, CsgA was modified to enable additional enzymatic or structural functions, such as the performance of a chemical reaction required for the synthesis of a drug or chemical. However, curli nanofiber-based materials thus far have not been developed for direct use as therapeutics.
“Naturally produced biofilms are known to hinder wound healing processes up to a point where they need to be actively managed by health care practitioners. We have essentially hacked one of the core machineries that produces them with the long-term goal to do exactly the opposite, to produce materials that could support wound healing in an environment that is inaccessible by other materials,” said first author Anna Duraj-Thatte, who is a Graduate School of Arts and Sciences postdoctoral fellow on Joshi’s team.