title_logo menu_logo
twitter
menu_bg



Member Profile

Chandan Sen

Personal Information
Title Professor
Expertise Wound Healing
Institution Ohio State University-Main Campus
Data Summary
TypeCount
Grants/SubContracts 2
Progress Reports 0
Publications 0
Protocols 0
Committees 1
Experiments 0
Strains 0
Models 0

SubContract(s)


DFU Recurrence
Diabetes increases susceptibility to infection and infection is a common complication of diabetic foot ulcers (DFU). About 85% of lower-limb amputations in patients with diabetes are preceded by infected foot ulceration. Emerging studies highlight the significant risk that biofilm infection poses to the non-healing DFUs. Using a preclinical swine model of mixed species wound biofilm infection, we struck an unusual observation. Although biofilm infection may or may not influence the rate of wound closure as measured by standard planimetry, it inevitably compromises the functional property of the repaired skin. The wound may close as evaluated visually, but that closed wound lacks barrier function. Such pathology is caused by the perturbation of epithelial junctional proteins in response to biofilm infection. While detecting the biofilm directly is readily not possible at present in the wound clinics, compromised barrier function of the repaired skin can be detected at the point of care of the measurement of trans-epidermal water loss (TEWL). This planning grant will therefore test the hypothesis that TEWL is a reliable biomarker of a history of biofilm infection in DFU. Wounds that appear closed with no discharge and are clinical decided to be closed, may suffer from compromised barrier function. Those that do suffer from such compromise are likely to reopen and contribute to wound recidivism. We propose planning activities including a pilot clinical study to develop a complete clinical study protocol that will be conducted on a collaborative basis between Ohio State and Stanford wound centers. The clinical study will address the following two specific aims testing the following hypotheses: Aim 1. Determine whether wound closure by re-establishment of functional skin is impaired in diabetic foot ulcers with a history of biofilm infection. Aim 2. Test if DFU recidivism is high in closed diabetic foot ulcers with defective barrier function.

Ossabaw miniature swine: Filling the void in the pre-clinical diabetic wound healing model
Current mechanistic study of diabetic wound healing relies on rodent models of diabetes, mostly acute hyperglycemia where systemic diabetic complications are not established. As diabetic wound complications soar resulting in loss of limb and life, it is critically important that we find relevant models that would enable invasive mechanistic studies. Metabolic syndrome (MetSyn) frequently co-exists in patients with diabetic wound complications. Swine models of diabetes have been reported but none of them exhibit insulin resistance. Furthermore, most rely on the use of chemical inducers of diabetes and are therefore complicated by side-effects of chemical toxicity. The Ossabaw swine are attractive models for MetSyn and manifest diabetic complications such as: (i) dysregulated energy metabolism; (ii) cardiovascular disorders including coronary atherosclerosis, and CAD; (iii) platelet hyper-aggregation; (iv) hepatic steatosis/ fibrosis, (v) polycystic ovary syndrome in females, and (vi) insulin resistance following high-fat cholesterol diet. This pilot proposal aims to perform comparative studies including Ossabaw porcine and diabetic patient-derived wound biopsies with the intent to validate Ossabaw miniswine as a pre-clinical model for diabetic wound complications. Two specific aims are proposed: Aim 1 Study biofilm dependent mechanisms that complicate wound perfusion. 1.1 The MetSyn Ossabaw wound microvasculature is sensitive to biofilm-infection induced leakiness. 1.2 Biofilm infection compromises pulse velocity of primary feeder arteries supplying the wound site. Aim 2 Compare and contrast findings of Aim 1 with those from diabetic patient-derived wound biopsies with the intent to test the validity of Ossabaw mini swine as a pre-clinical model for diabetic wound complications.


Progress Reports

No funding program application progress reports found.

Annual Reports

No uploaded documents found.

No publications found.

No uploaded documents found.

No protocols found.

No experiments found.

No strains found.

No models found.