Research Projects

Diabetic foot infection (DFI), closely related to diabetic foot ulcers (DFU), is a leading cause of morbidity and mortality in diabetic patients. Reported rates of DFU infections in India vary from 85 to almost 100%, of which 15% require amputation. In India, the prevalence of DFI is thus approximately 6.2%, contributing to over 80% of non-traumatic amputations annually. Demographic impact on DFI prevalence is noticeable, with rates of 9.5% in eastern, 7.4% in southern and 5.6% in northern India, while western India has the lowest prevalence (~1.5%), due to factors ambiguous so far. The 5-year mortality rate ranges from 29-69% after minor amputations to 52-80% after major amputations. Thus, understanding the pathophysiology of DFI is crucial to improving patient outcomes. Recent foreign studies have indicated that host immune status is a major deciding factor for healing of DFIs due to inherent infection and chronic inflammation. Analysis of host immune factors between healing and non-healing DFIs, in connection with the pathogenic profile and demographic factors, will provide novel insights into the lower prevalence of DFIs in Western India as compared to the East. With India projected to have ~124.9 million diabetics by 2045, understanding the basis of lower DFI prevalence in Western India and pitting potent phytoextracts from Odisha coast against non-healing wounds, will provide novel and improved therapeutics. We hypothesize that the host immune response to DFI in Western India differs from that in the East, with host immunomodulation playing a major pathogenic role. This study aims to identify the demographic difference in host response to DFI and explore the potential of phytoextracts in promoting wound healing. The objectives are: 1) Analyze the DFI host immunomodulation using RNA-seq transcriptomics and targeted proteomics; 2) Study mechanism of wound healing pathways involved in DFI using a 3D bioprinted skin model; and 3) Evaluate the healing effects of selected phytoextracts on DFI wounds. The study will collect 100 wound debridement and blood samples from DFI patients with over 5 years of diabetes from JIPMER, Puducherry (Western India) and AIIMS, Bhubaneswar (Eastern India). RNA-seq transcriptomics and proteomics at the beginning and after 8 weeks will assess host immune-related genes and wound healing players from healing and non-healing patients. After identifying key pathways, the healing effects of selected phytoextracts will be tested in a 3D skin model and an in vivo animal model. Outcome: This research will provide valuable insights into demographic differences in host response underlying healing and non-healing DFIs in India, while offering a 3D bioprinted skin model for studying DFI/DFU and other skin infections. The findings could lead to more effective and locally relevant treatments, potentially introducing new therapies that are both clinically and economically viable for the Indian healthcare system.