Extended Release of Bioactive Factors to Treat Refractory Wounds

延长释放生物活性因子来治疗难治性伤口

• 批准号: 9924291
• 负责人: Yadong Wang
• 金额: $ 37.77万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-22 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924291
• 关键词: Abnormal Cell; Anatomy; Animal Model; Antibiotics; Area; Becaplermin; Blood Vessels; Caregivers; Caring; Cell Proliferation; Cell secretion; Cells; Chronic; Cicatrix; Clinical; Collagen; Complex; Consumption; DTR gene; Debridement; Deposition; Dermal; Diabetes Mellitus; Diabetic Foot Ulcer; Discipline of Nursing; Dorsal; Dose; Emulsions; Engineering; Environment; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cell Proliferation; Epithelium; Excision; Excretory function; Exhibits; Family suidae; Fascia; Fibroblasts; Foundations; Frequencies; Goals; Granulation Tissue; Growth Factor; Health; Health Care Costs; Healthcare; Heparin; Heparin Binding; Human; In Vitro; Individual; Inflammation; Infusion procedures; Interruption; Lead; Literature; Lower Extremity; Measures; Metabolism; Modeling; Morbidity - disease rate; Mus; Muscle; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Measure; Oxidative Stress; Patients; Phenotype; Physiological; Play; Process; Property; Protein Analysis; Proteins; Protocols documentation; Quality of life; Receptor Down-Regulation; Refractory; Research; Role; Safety; Science; Self Management; Signal Transduction; Site; Skin; Skin wound healing; Streptozocin; Structure of beta Cell of islet; System; Tensile Strength; Testing; Thick; Time; Treatment Cost; Treatment Efficacy; Treatment outcome; Type 2 diabetic; Wound models; absorption; angiogenesis; base; cell killing; cell motility; chronic wound; clinically relevant; cost; design; diabetic; diabetic patient; diabetic wound healing; disability; dosage; efficacy testing; healing; improved; infection risk; innovation; insight; keratinocyte; limb amputation; mouse model; new technology; novel strategies; open wound; pressure; productivity loss; prototype; response; self reliance; side effect; skin wound; stem cells; success; tissue repair; translational study; wound; wound care; wound closure; wound healing

Extended release of bioactive factors to treat refractory wounds Chronic wounds significantly decrease quality of life, lead to severe disability, and are huge burdens on healthcare and caregivers. Diabetes mellitus is expected to afflict 366 million people worldwide by 2030. Among these patients, approximately 15% will develop diabetic foot ulcers. Underlying chronic wounds, abnormal cell phenotypes and chronic inflammation inhibit normal healing processes and elevate the risk of infection. Current clinical solutions are expensive, time-consuming, largely unsuccessful, and lack patient self-management. The overarching goal of this translational study is to advance nursing science and the wound care field, by healing chronic wounds with one-time administration of sustained, local release of growth factors. This effective and economical treatment will be achieved using a new vehicle that protects the bioactivity of the protein cargo. Growth factor signaling plays a pivotal role in the natural wound healing process. The major limitation in growth factor therapies has been the lack of an appropriate delivery system to provide for prolonged signaling. Controlled delivery of growth factor will reduce patient morbidity and risk of infection in chronic wounds while helping patients to manage their care more autonomously. This research focuses on testing the efficacy of a delivery system we recently designed for wound-implicated growth factors and has three specific aims: Aim 1. Investigate the effects of HB-EGF coacervate on wound healing in vitro using normal and diabetic primary human dermal cells and evaluate the safety of the coacervate treatment. Aim 2. Evaluate the efficacy of controlled delivery of HB-EGF to improve diabetic wound healing in a polygenic type 2 diabetic mouse model. Aim 3. Investigate the controlled delivery of HB-EGF to accelerate diabetic wound healing in a porcine model. This proposal will provide the foundation for an easy-to-use product that significantly improve healing of wounds, increase patient self-reliance and quality of life, and reduce the interruption and loss of productivity patients currently must accept. Therefore, this new technology would enable not only improved health outcomes, but also more self-management for individuals with chronic wounds.

生物活性因子缓释治疗难治性创面 慢性伤口显著降低生活质量，导致严重残疾， 对医疗保健和护理人员造成巨大负担。糖尿病预计将困扰3.66亿人 到2030年，全世界在这些患者中，大约15%会发展为糖尿病足 溃疡潜在的慢性伤口，异常细胞表型和慢性炎症抑制 正常的愈合过程，并增加感染的风险。目前的临床解决方案是 昂贵、耗时、大部分不成功，并且缺乏患者自我管理。的 这项转化研究的首要目标是推进护理科学和伤口护理 场，通过愈合慢性伤口，一次性持续给药，局部释放生长 因素这种有效和经济的治疗将实现使用一种新的车辆， 蛋白质货物的生物活性。 生长因子信号传导在自然伤口愈合过程中起着关键作用。的 生长因子治疗的主要限制是缺乏合适的递送系统 提供延长的信号。生长因子的控制输送将降低患者发病率 和慢性伤口感染的风险，同时帮助患者更好地管理护理 自主地。这项研究的重点是测试一种输送系统的有效性，我们最近 设计用于创伤相关生长因子，并具有三个具体目标： 目标1.体外实验观察HB-EGF凝聚物对创面愈合的影响， 糖尿病原代人真皮细胞，并评估凝聚层处理的安全性。 目标2.评价HB-EGF控制性释放促进糖尿病伤口愈合的疗效 在多基因2型糖尿病小鼠模型中。 目标3。研究HB-EGF的控制递送以加速糖尿病伤口愈合， 猪模型 该提案将为易于使用的产品提供基础， 改善伤口愈合，提高患者的自立能力和生活质量，并减少 患者目前必须接受的中断和生产力损失。因此，这项新技术 不仅可以改善健康状况，还可以提高个人的自我管理能力 慢性伤口。

项目成果

Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical Applications.

• DOI: 10.1039/c6tb03052a
• 发表时间: 2017-02-07
• 期刊: Journal of materials chemistry. B
• 作者: Ding X;Wang Y
• 通讯作者: Wang Y

A biocompatible betaine-functionalized polycation for coacervation.

用于凝聚的生物相容性甜菜碱官能化聚阳离子。

• DOI: 10.1039/c7sm01763d
• 发表时间: 2018-01-17
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Hwang MP ;Ding X ;Gao J ;Acharya AP ;Little SR ;Wang Y
• 通讯作者: Wang Y

The matricellular protein decorin delivered intradermally with coacervate improves wound resolution in the CXCR3-deficient mouse model of hypertrophic scarring.

基质细胞蛋白核心蛋白聚糖通过凝聚层皮内递送，改善了 CXCR3 缺陷小鼠肥厚性疤痕模型的伤口消退。

• DOI: 10.1111/wrr.13017
• 发表时间: 2022
• 期刊: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
• 作者: Sylakowski,Kyle;Hwang,MintaiPeter;Justin,Amritha;Whaley,Diana;Wang,Yadong;Wells,Alan
• 通讯作者: Wells,Alan