Jignesh Parvadia

Role of salivary vascular endothelial growth factor (VEGF) in palatal mucosal wound healing.

The mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss‐of‐function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss‐of‐function experiment using the protein VEGF‐Trap to inhibit salivary VEGF. In a gain‐of‐function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF‐Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary‐VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.

In Situ Tissue Engineering Using Angiogenic Nanoscaffold Enhances Diabetic Wound Healing in db/db Mouse Model

Tissue engineering offers an attractive alternative for treatment of chronic nonhealing diabetic ulcers, which account for more than 27% of the

The Effect of Steroid-Antibiotic Agents on Granulation Tissue in a Murine Model

10.9 billion total diabetic health care costs in the US annually [1]. The harsh environment of a diabetic ulcer is characterized by reduced expression of angiogenic factors, insufficient vascularization, excess protease activity, matrix degradation and hyperglycemia-induced cell apoptosis [2]. A major factor contributing to insufficient neovascularization in diabetic nonhealing wounds may be deficiency in the recruitment of endothelial cells (ECs) and endothelial precursor cells (EPCs) to the wound site [3]. Recent studies focusing on altering the wound’s cellular and molecular environment using bone-marrow-derived stem cells, growth factors (delivered either directly or using gene or cell therapy), bioengineered skin constructs, and biological matrices, such as collagen and hyaluronic acid gels had promising wound healing outcomes [4]. These studies suggest that strategies aimed at modifying the extracellular environment of the diabetic wound to enhance cell survival and angiogenesis are promising for development of new therapies for diabetic wound healing.Copyright

Effect of Corticosteroid-Antibiotic Agents on Granulation Tissue in a Murine Model

Abstract Problem: Many ototopical steroid-antibiotic agents (OSAAs) are currently available for use in the treatment of inflammatory conditions of the external and middle ear. The objective of this study was to compare the effects of 3 commonly used OSAAs on granulation tissue in an established murine model of wound healing. We hypothesized that all of the study OSAAs would demonstrate similar efficacy in the inhibition of granulation tissue formation. Methods: Eight-millimeter wounds were created bilaterally on the flanks of 12 C57BL/6J mice. Wounds were treated with CiproDex (ciprofloxacin/dexamethasone), TobraDex (tobramycin/dexamethasone), CiproHC (ciprofloxacin/hydrocortisone), or saline (n = 6 each) for 3 days (days, 4–6) and then harvested on day 7. Wound sections were stained with hematoxylin and eosin, Gomori’s trichrome (extracellular matrix [ECM] deposition), or anti-CD31 antibodies (endothelial cells). Extracellular matrix deposition was graded from 1–4 and neovascularization was assessed by counting the number of endothelial-lined vessel lumens per high power field (hpf). Results: The mean grade (± standard error of the mean) of ECM deposition was lower in wounds treated with CiproDex (1.7 ± 0.2) and TobraDex (2.0 ± 0.2) but not with CiproHC (2.9 ± 0.3) compared to controls (2.9 ± 0.2) ( P P Conclusion: All 3 OSAAs studied were equally effective at reducing neovascularization although dexamethasone-based products were more effective at reducing ECM deposition. Significance: The results of this study suggest that ototopical agents containing dexamethasone may be more effective for the treatment of granulation tissue resulting from external and middle ear inflammatory conditions. Support: None reported.