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

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）：氧气在伤口愈合中起着重要作用，越来越多的证据表明，组织氧合水平是皮肤愈合反应中的重要限速因素。具体地，不愈合的糖尿病慢性伤口（定义为持续> 6周）。通常表现出极低的氧浓度，低至5 mmHg氧分压（PO 2）。糖尿病影响着超过2500万美国人，预计在未来五年内每年将增加100万至200万例。据估计 高达25%的糖尿病患者会出现足部溃疡，其中五分之一的患者会导致慢性不愈合的伤口，需要截肢。氧治疗已被证明通过增强代谢、ECM合成和新血管形成而促进慢性伤口愈合，同时限制抗微生物活性。尽管补充氧气的好处，目前的氧气输送治疗是间歇性的，不方便的病人，并需要访问昂贵的和专门的设备。非常需要一种简单的伤口护理敷料，其能够支持再生水平的氧气并补充或可能取代当前的治疗（高压氧，通过帐篷/袋的局部氧气）。该提案提供了一种敷料形式的基于UV聚合水凝胶的方法，该方法有可能在整个伤口上提供均匀和可调的氧合。我们最近发明了一种具有生物相容性的光交联壳聚糖与特殊的化学添加剂。我们的方法是创新的，因为它允许创建可注射/可模塑的水凝胶伤口敷料，可以维持伤口愈合的氧气水平超过12小时，并可能长达5天。我们的主要假设是，我们的载氧水凝胶平台将比无氧支架或商业敷料（Puracol Plus（r））更快、更完全地提供增强的短期和长期皮肤愈合反应。为了验证这些假设，R15区域提案有四个具体目标：1。制备壳聚糖基氧气输送水凝胶并对其性能进行表征; 2.体外精制水凝胶; 3.进行临床前体内概念验证研究，以评估水凝胶在伤口愈合中的安全性和有效性; 4.让研究生、本科生和高中生参与生物医学研究的各个领域。从方便的水凝胶敷料提供氧气的能力可以改变慢性伤口愈合，同时为研究氧气在纠正其他组织损伤，疾病或病症中的作用提供新的工具。

项目成果

Fluorinated Methacrylamide Chitosan Hydrogel Dressings Improve Regenerated Wound Tissue Quality in Diabetic Wound Healing.

• DOI: 10.1089/wound.2018.0887
• 发表时间: 2019-07
• 期刊: Advances in wound care
• 影响因子: 4.9
• 作者: P. S. Patil;Shahrzad Fathollahipour;A. Inmann;Anup D. Pant;Rouzbeh Amini;L. Shriver;Nic D. Leipzig

Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules.

• DOI: 10.1021/acsami.5b10070
• 发表时间: 2016-02
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Lawrence PG;Patil PS;Leipzig ND;Lapitsky Y
• 通讯作者: Lapitsky Y

Fluorinated Chitosan Microgels to Overcome Internal Oxygen Transport Deficiencies in Microtissue Culture Systems.

• DOI: 10.1002/adbi.201900250
• 发表时间: 2020-08
• 期刊: ADVANCED BIOSYSTEMS
• 影响因子: 4.1
• 作者: Patil, Pritam S.;Mansouri, Mona;Leipzig, Nic D.
• 通讯作者: Leipzig, Nic D.

Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability.

• DOI: 10.1016/j.actbio.2016.03.022
• 发表时间: 2016-05
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Patil PS;Fountas-Davis N;Huang H;Michelle Evancho-Chapman M;Fulton JA;Shriver LP;Leipzig ND
• 通讯作者: Leipzig ND

Fluorinated methacrylamide chitosan hydrogel dressings enhance healing in an acute porcine wound model.

• DOI: 10.1371/journal.pone.0203371
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Patil PS;Evancho-Chapman MM;Li H;Huang H;George RL;Shriver LP;Leipzig ND
• 通讯作者: Leipzig ND