Research Projects

Optimizing wound care requires addressing the absence of a universally accepted gold standard for dressing application. Patients face significant challenges, including severe pain, infection risk, fluid loss, and multi-system organ dysfunction, which complicate the treatment. Although various wound dressings exist, however, many standard dressings compromise wound oxygenation, resulting in hypoxia within regenerating epithelial cells. Many pathogenic bacteria colonize open or compromised wounds among which, Pseudomonas aeruginosa (PAO1), a gram negative multi drug-resistant pathogen is one of the major culprits causing sepsis. The bacterium uses Wsp signal transduction mechanism which helps the bacteria adapt to the new environment and start forming biofilms by quorum sensing. Probiotic bacteria, Lactobacillus plantarum exerts multifaceted functions through its outer membrane vesicle (OMV) proteins. In our preliminary studies we have found that L. plantarum derived outer membrane vesicles (OMVs) inhibit PAO1 biofilm formation. Additionally, in-silico analysis of interaction between OMV derived proteins of L. plantarum and P. aeruginosa presented a protein, 1YTR (bacteriocin) interacting with Wsp A and Pil Q/F. This protein may have a role in inhibiting these two major surface sensing systems of PAO1, i.e., Wsp and Pil-Chp, major signalling cascades resulting biofilm formation by EPS biosynthesis, motility and virulence. The physiological environment surrounding a wound presents inherent challenges to adjacent cells, characterized by compromised vasculature, hypoxia, inflammation, and edema. Persistent hypoxic conditions impede the healing process by inhibiting the formation of new blood vessels. Thus, tackling the issue of hypoxia shall be our primary objective. Conventional wound dressings, such as bandages, establish a barrier that impedes the influx of atmospheric oxygen. The limited oxygen availability within engineered composites continues to present a significant obstacle in the fields of tissue engineering and regenerative medicine. A challenge of encapsulating O2, a highly diffusible gas within carrier molecules is acknowledged by the proposed research utilizing a multi-carrier approach. The Maillard reaction facilitates the browning of Bovine Serum Albumin (BSA), which serves as the foundation for nano-oxygen-bubbles (NOBs), encapsulating molecular oxygen. Subsequently, these NOBs will be integrated into bilayered outer membrane vesicles (OMVs) derived from the probiotic bacterium L. plantarum LP2621. The resulting oxygen-incorporated-probiotic-OMV (OPO) nanovesicles will be then incorporated into a hyaluronic acid based hydrogel to create the OPO-gel composite. Therefore, our proposed multifunctional novel hydrogel incorporates antibacterial agents (borax, probiotic OMVs), bioactive molecules (Hyaluronic acid), and enhanced oxygen delivery properties (Oxygen loaded Probiotic OMVs (OPO). Histological, biochemical, and molecular assays will validate the efficacy of the synthesized OPO hydrogel in a Wistar rat wound model. Integrated transcriptomic-proteomic profiling during wound repair phases will provide with insightful information about the differential expression of mRNA/proteins during the wound healing process. The development of a superior wound dressing that accelerates healing as well as inhibits serious bacterial infections will be our paramount goal. Secondary goals include modifying hydrogel’s composition to improve stability, biocompatibility, and usability based on experimental findings. to conduct a multi-tiered validation study using large animals such as pigs and cohort human population. The cohort population study will be carried out to find out the efficacy and safety of the proposed hydrogel, thus strengthening the credibility of clinical translation.