Adaptable Hydrogel Oxygen Delivery Platform for Wound Care

用于伤口护理的适应性水凝胶氧气输送平台

• 批准号: 8574636
• 负责人: Nic D Leipzig
• 金额: $ 35.83万
• 依托单位: UNIVERSITY OF AKRON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8574636
• 关键词: Affect; American; Amputation; Area; Bandage; Biocompatible; Biocompatible Materials; Biological Assay; Biomedical Research; Caring; Cell Count; Cells; Cellulose; Characteristics; Chitosan; Chronic; Collagen; Data; Dermal; Diabetes Mellitus; Dimensions; Disease; Engineering; Environment; Enzymes; Equipment; Evaluation; Exposure to; Extracellular Matrix; Family suidae; Fibroblasts; Fluorocarbons; Foot Ulcer; Goals; Healed; Human; Hydrogels; Hyperbaric Oxygenation; Hypoxia; In Vitro; Inflammatory; Injectable; Injury; Institution; Kinetics; Measures; Mechanics; Metabolic; Metabolism; Methodology; Modeling; Oxygen; Partial Pressure; Patients; Play; Property; Public Health; Research; Role; Safety; Scientist; Simulate; Site; Skin; Solutions; Sterile coverings; Students; Suspension substance; Suspensions; Swelling; Techniques; Testing; Thick; Time; Tissues; Ultraviolet Rays; United States National Institutes of Health; Work; Wound Healing; antimicrobial; base; chemical addition; clinically relevant; cytokine; diabetic; healing; high school; improved; in vivo; innovation; keratinocyte; methacrylamide; neovascularization; next generation; novel; pre-clinical; programs; public health relevance; regenerative; response; scaffold; tissue oxygenation; tool; uptake; wound; Affect; American; Amputation; Area; Bandage; Biocompatible; Biocompatible Materials; Biological Assay; Biomedical Research; Caring; Cell Count; Cells; Cellulose; Characteristics; Chitosan; Chronic; Collagen; Data; Dermal; Diabetes Mellitus; Dimensions; Disease; Engineering; Environment; Enzymes; Equipment; Evaluation; Exposure to; Extracellular Matrix; Family suidae; Fibroblasts; Fluorocarbons; Foot Ulcer; Goals; Healed; Human; Hydrogels; Hyperbaric Oxygenation; Hypoxia; In Vitro; Inflammatory; Injectable; Injury; Institution; Kinetics; Measures; Mechanics; Metabolic; Metabolism; Methodology; Modeling; Oxygen; Partial Pressure; Patients; Play; Property; Public Health; Research; Role; Safety; Scientist; Simulate; Site; Skin; Solutions; Sterile coverings; Students; Suspension substance; Suspensions; Swelling; Techniques; Testing; Thick; Time; Tissues; Ultraviolet Rays; United States National Institutes of Health; Work; Wound Healing; antimicrobial; base; chemical addition; clinically relevant; cytokine; diabetic; healing; high school; improved; in vivo; innovation; keratinocyte; methacrylamide; neovascularization; next generation; novel; pre-clinical; programs; public health relevance; regenerative; response; scaffold; tissue oxygenation; tool; uptake; wound

DESCRIPTION (provided by applicant): Oxygen plays a significant role in wound healing and growing evidence shows that tissue oxygenation levels are an important rate limiting factor in the dermal healing response. Specifically, non-healing diabetic chronic wounds (defined as lasting > 6 wks.) often show devastatingly low oxygen concentrations, as low as 5 mmHg oxygen partial pressure (PO2 ). Diabetes affects more than 25 million Americans and is forecasted to increase by 1-2 million cases each year for the next five years. It is estimated that up to 25% of all diabetics will develop a foot ulcer, and a fifth of these cases will result in a chronic non-healing wound that requires amputation. Oxygen treatment has been demonstrated to promote chronic wound healing by enhancing metabolism, ECM synthesis and neovascularization, while limiting antimicrobial activity. Despite the benefits of supplemental oxygen, current oxygen delivery therapies are intermittent, inconvenient for the patient, and require access to expensive and specialized equipment. There is significant need for a simple wound care dressing able to support regenerative levels of oxygen and to supplement or possibly supplant current therapies (hyperbaric oxygen, topical oxygen via tent/bag). This proposal provides a UV polymerized hydrogel-based methodology in the form of a dressing that has the potential to provide uniform and tunable oxygenation across the wound. We have recently invented a biocompatible photocrosslinkable chitosan with special chemical additions. Our approach is innovative because it allows the creation of injectable/moldable hydrogel wound dressings that can sustain healing levels of oxygen to a wound for greater than 12 h, and potentially up to 5 d. Our primary hypothesis is that our oxygen loaded hydrogel platform will provide both enhanced short-term and long-term skin healing responses significantly faster and more completely than unoxygenated scaffolds or a commercial dressing (Puracol Plus(r)). To test these hypotheses, this R15 AREA proposal has four specific aims: 1. To create chitosan based oxygen delivery hydrogels and characterize their properties; 2. To refine the hydrogels in vitro; 3. To conduct preclinical in vivo proof of concept studies to evaluate safety and efficacy o the hydrogels in wound healing; 4. To engage graduate, undergraduate and high school students in various areas of biomedical research. The ability to supply oxygen from a convenient hydrogel dressing could transform chronic wound healing while providing new tools for studying the role of oxygen in correcting other tissue injuries, disease or disorders.

描述（由申请人提供）：氧气在伤口愈合和越来越多的证据中起着重要作用，表明组织氧合水平是皮肤愈合反应中重要的速率限制因素。具体而言，非愈合的糖尿病慢性伤口（定义为持久> 6 wks）通常显示出毁灭性的低氧浓度，低至5 mmHg氧氧局部压（PO2）。糖尿病会影响超过2500万美国人，预计未来五年每年将增加1-200万病例。据估计 所有糖尿病患者中有25％将出现足球溃疡，其中五分之一将导致慢性非治疗伤口需要截肢。已经证明氧处理可以通过增强代谢，ECM合成和新血管形成，同时限制抗菌活性，从而促进慢性伤口愈合。尽管有补充氧气的好处，但当前的氧气输送疗法是间歇性的，对患者带来了不便，需要使用昂贵且专业的设备。非常需要简单的伤口护理敷料能够支持再生水平的氧气并补充或可能取代当前疗法（高压氧，通过帐篷/袋子的局部氧）。该提案以敷料的形式提供了一种基于紫外线聚合的水凝胶方法，该方法具有在伤口上提供均匀可调的氧合的潜力。我们最近发明了一种具有特殊化学添加的可生物相容性光叠链式壳聚糖。我们的方法具有创新性，因为它允许创建可注射/可塑造的水凝胶伤口敷料，这些敷料可以维持伤口的愈合水平超过12小时，并且可能最多可达5 d。我们的主要假设是，与非氧合脚手架或商业敷料相比，我们的氧气负载水凝胶平台将显着更快，更全面地提供增强的短期和长期皮肤愈合反应（Puracol Plus（R））。为了检验这些假设，该R15区域提案具有四个特定的目的：1。创建基于壳聚糖的氧气递送水凝胶并表征其性质； 2。在体外完善水凝胶； 3。进行临床前体内概念证明，以评估伤口愈合中水凝胶的安全性和有效性； 4。参与生物医学研究各个领域的毕业生，本科和高中生。从方便的水凝胶敷料中供应氧气的能力可以改变慢性伤口愈合，同时提供新的工具来研究氧气在纠正其他组织损伤，疾病或疾病中的作用。