Conference Proceeding

Modulation of Angiogenesis and Secretory Control in Diabetic Wound Healing through Fibrin-in-fibrin System

Dr. Mangesh Kulkarni

Wound healing in diabetes is compromised and poses a major clinical problem. Despite rigorous treatment regimes, there has been modest success in reducing the rate of amputations in these patients. This work attempted to unravel the molecular disarray in wounded keratinocytes under hyperglycemic conditions and subsequently to develop a non-viral gene delivery system capable of delivering therapeutic genes in an extended manner. Using a modular approach, we first tested a fibrin lipoplex system for simultaneous delivery of multiple genes, both in vitro and in vivo. To build up further, desired features were temporal control and increased DNA loading capacity. Towards this goal, fibrin microspheres loaded with gene complexes were successfully developed and investigated for functional gene delivery in vivo using proangiogenic gene – eNOS.

A profoundly significant differential gene regulation was found from the microarray data analysis on the wounded keratinocytes under hyperglycemic culture conditions. Of the most important and functionally relevant ones, Rab18, a molecule involved in controlling secretion, was found to be significantly down regulated. Considering the hypersecretory state of proinflammatory cytokines and proteolytic enzymes in diabetic wound healing, Rab18 was chosen as target therapeutic gene. eNOS was chosen as other therapeutic gene, considering its proangiogenic action and impaired angiogenesis in diabetic wound healing. A fibrin-in-fibrin system was developed with eNOS gene complexes in fibrin gel and Rab18 gene complexes in fibrin microspheres embedded in fibrin gel. The Rab18-eNOS loaded fibrin-in-fibrin system was investigated in alloxan induced hyperglycemic rabbit ear ulcer model of compromised wound healing. Rab18- eNOS treated group showed significantly higher percent wound closure at day 14 post wounding with reduced inflammatory cell infiltrate and more functional angiogenesis. Thus, a proangiogenic secretory control approach mediated through fibrin is promising in improving outcome in diabetic wound healing.

Published: 17 October 2017

Copyright:

Copyright: © 2017 Dr. Mangesh Kulkarni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.