The etiology of chronic wounds is generally multi-factorial of which hypoxia is a common factor. Clinical conditions involving hypoxic wound include peripheral vasculopathy (diabetics, arteriosclerosis, etc.), post- operative recovery, and arterial hypoxia (e.g. pulmonary fibrosis or pneumonia, sympathetic pain response, hypothermia, major blood loss, cyanotic heart disease, high altitude). This proposal addresses the significance of O2 in wound healing of such cases. The proposal has two facets: understanding oxygen- sensitive mechanisms in the wound, and developing approaches for wound oxygenation. For the first time, the highly significant hemoglobin-based HBOC (""""""""artificial blood"""""""") technology is being studied for wound oxygenation. The central hypothesis is that wound oxygenation is a key determinant of wound angiogenesis. Chronic ischemic wounds are typically hypoxic. While hypoxia acutely triggers the expression of angiogenic factors and responses, long-term hypoxia cannot sustain the formation of new functional vasculature resulting in wound chronicity. Correction of wound hypoxia supports healing.
Aims 1 and 2 rest on the observation that hypoxia in mice impairs the healing of full thickness dermal wounds. Correction of hypoxia, restored wound closure.
Aim 3 is based on similar observations in a pre-clinical swine model of ischemic wound. The following three aims are proposed:
AIM 1. Characterize the effects of tissue oxygenation on the preparation for wound angiogenesis: i. Establish the effects of tissue oxygenation on wound closure;ii. Examine the effects of tissue oxygenation on the preparation for wound angiogenesis in the early inflammatory phase;iii. Test the role of hypoxia-inducible factor (HIF) in wound angiogenesis under conditions of hypoxia.
AIM 2. Determine the mechanisms by which the state of tissue oxygenation influences wound angiogenesis in the late tissue-remodeling phase: i. Determine the significance of hypoxia-induced inhibition of dermal wound TGFbl;ii. Investigate the role of low wound-site NO production under conditions of limited O2.
AIM 3. Test whether oxygenation of wounds influences full-thickness dermal wound healing in a pre-clinical swine model of ischemic wound: i. Test whether local application of O2 (gas-based and HBOC- based approaches) corrects full-thickness wound hypoxia;ii. Determine whether oxygenation accelerates wound closure;iii. Determine if correction of wound hypoxia facilitates angiogenesis and blood flow.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM077185-03
Application #
7623542
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Ikeda, Richard A
Project Start
2007-08-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
3
Fiscal Year
2009
Total Cost
$264,000
Indirect Cost
Name
Ohio State University
Department
Surgery
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Das Ghatak, Piya; Mathew-Steiner, Shomita S; Pandey, Priyanka et al. (2018) A surfactant polymer dressing potentiates antimicrobial efficacy in biofilm disruption. Sci Rep 8:873
Sinha, Mithun; Sen, Chandan K; Singh, Kanhaiya et al. (2018) Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nat Commun 9:936
Li, Jilong; Ghatak, Subhadip; El Masry, Mohamed S et al. (2018) Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound. Mol Ther 26:2178-2188
Das, Amitava; Datta, Soma; Roche, Eric et al. (2018) Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage polarization and resolution of wound inflammation. Sci Rep 8:1696
Gnyawali, Surya C; Blum, Kevin; Pal, Durba et al. (2017) Retooling Laser Speckle Contrast Analysis Algorithm to Enhance Non-Invasive High Resolution Laser Speckle Functional Imaging of Cutaneous Microcirculation. Sci Rep 7:41048
Barki, Kasturi Ganesh; Das, Amitava; Dixith, Sriteja et al. (2017) Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing. Ann Surg :
Singh, Kanhaiya; Pal, Durba; Sinha, Mithun et al. (2017) Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy. Mol Ther 25:2689-2704
Gallego-Perez, Daniel; Pal, Durba; Ghatak, Subhadip et al. (2017) Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nat Nanotechnol 12:974-979
Blackstone, Britani N; Kim, Jayne Y; McFarland, Kevin L et al. (2017) Scar formation following excisional and burn injuries in a red Duroc pig model. Wound Repair Regen 25:618-631
Ahmed, Noha S; Ghatak, Subhadip; El Masry, Mohamed S et al. (2017) Epidermal E-Cadherin Dependent ?-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling. Mol Ther 25:2502-2512

Showing the most recent 10 out of 88 publications