Mechanisms Regulating Wound Vascularization

Study Overview
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Brief Summary
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This pilot study is designed to assess the impact of ischemia/ diminished wound vascularization and stress on wound healing by comparing patterns of gene expression in specific cell types critical to wound healing biology, e.g. macrophages or endothelial cells.

Detailed Description
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Chronic wounds affect approximately 2% of the U.S. population at any given time. Animal models can not simulate the complex set of pre-existing conditions in each individual that results in failed wound healing. Therefore, human subjects must be used to obtain valid data. Adequate wound vascularization that permits blood vessels to deliver oxygen to the wound is a requirement for wound healing to occur. This protocol will attempt to gain greater understanding of the mechanisms of chronic wounds through 3 specific aims: 1) identify the angiogenic mechanisms in wound site macrophages, which are required for healing, 2) determine the impact of stress and glucocorticoid resistance on endothelial cell and macrophage biology and ultimately wound healing outcomes, 3) identify patterns of gene expression in wound endothelial cells that are found in healing versus non-healing wounds. This data will be correlated with the wound oxygenation status to determine the impact of wound vascularization on the observed biological responses.

Official Title
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Mechanisms Regulating Wound Vascularization

Conditions
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Wounds and Injuries

Intervention / Treatment
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* Procedure: Samples will be collected


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-69 years ischemic wound group non-ischemic wound group diabetes with good glycemic control lower extremity wound Exclusion Criteria: Age greater ≥ 70 years End stage renal disease Unable to provide informed consent Pregnant women Therapeutically anticoagulated Prisoners Periwound TcOM < 25mmHg Spinal cord injury Taking immunosuppressive medications Individuals with current diagnosis of a major psychiatric illness (e.g.schizophrenia,psychosis) Severe protein malnutrition- pre-albumin < 10 mg/dl or albumin < 2 g/dl Diabetes with poor glucose control-defined as hgb A1c > 8.4%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 2- Diabetics without wound (s)<br>These group of subject will be control arm, included who have good glycemic control diabetic with HbA1c 8.4 or lower and also without any open wounds. Samples will be collected. | Procedure: Samples will be collected<br>* wound tissue biopsy, blood samples, saliva collection and wound VAC sponge (if applicable).<br>|
| 1-Subjects with diabetes with wound<br>This group of subjects will have wound and come for couple of follow up visits for saliva collection, biopsy collection and blood draw. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Gene Expression Profile in Healing versus Non-healing Wounds | Wound tissue biopsies, saliva, serum samples and wound sponges will be obtained at an initial time point, at the midpoint of the study and near the end of wound closure over a 12 week window. If the wound closes quickly, i.e. less than 4 weeks then only 2 biopsies will be obtained. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Impact of ischemia, Impact of stress and, Identify patterns of gene expression