Telemetric Regenerative Bandage for Accelerating Wound Healing

用于加速伤口愈合的遥测再生绷带

• 批准号: 10346507
• 负责人: Guillermo Antonio Ameer
• 金额: $ 64.9万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-24 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10346507
• 关键词: Acrylamides; Address; Adhesions; Amputation; Animal Model; Animals; Antioxidants; Attenuated; Bacterial Infections; Bandage; Biocompatible Materials; Blood Circulation; Body Temperature; Caring; Cells; Chronic; Citrates; Clinic; Clinical; Complications of Diabetes Mellitus; Copper; Dermal; Development; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic mouse; Digit structure; Disease; Endothelial Cells; Engineering; Exposure to; Family suidae; Feedback; Fibroblasts; Free Radicals; Gel; Goals; Health; Healthcare; High Prevalence; Hospitals; Human; Immobilization; Impaired healing; Impaired wound healing; Impairment; Implant; In Vitro; Incidence; Infection; Inflammation; Laminin; Lead; Left; Limb structure; Location; Lower Extremity; Measures; Medical Device; Metabolic syndrome; Metals; Miniature Swine; Monitor; Operative Surgical Procedures; Oxidative Stress; Patient-Focused Outcomes; Patients; Peptides; Personal Satisfaction; Physicians; Polyethylene Glycols; Population; Positioning Attribute; Prevalence; Process; Property; Research; Research Personnel; Safety; Sepsis; Shapes; Skin; Skin wound healing; Societies; Specific qualifier value; Sterile coverings; Stretching; System; Telemetry; Temperature; Testing; Thick; Time; Tissues; Vascularization; Wireless Technology; Work; Wound Infection; angiogenesis; base; biomaterial compatibility; blood perfusion; clinically relevant; db/db mouse; diabetes amputation; diabetic; diabetic ulcer; effective therapy; flexibility; healing; health care delivery; health care disparity; human disease; improved; innovation; keratinocyte; limb amputation; macromolecule; microsensor; migration; mouse model; nanoparticle; nanoparticle delivery; neovascularization; non-healing wounds; novel; outcome prediction; porcine model; prevent; regenerative; research clinical testing; scaffold; sensor; skin wound; therapy outcome; tissue regeneration; tool; wound; wound bed; wound care; wound closure; wound dressing; wound healing

Summary Diabetic foot ulcers (DFUs) are a major complication of diabetes. These sores, if left untreated, can become infected and become a serious threat to the patient’s well being. Although the field of wound care management is well established, the effective treatment of chronic DFUs remains a challenge. The primary goal in the treatment of DFUs is for the wound to close as soon as possible and to do so in a durable way. However, prolonged inflammation, oxidative tissue damage, and impaired blood circulation in diabetic wounds delay the wound healing process, resulting in open, non-healing wounds that often lead to limb amputations. This proposal will address these problems by developing a versatile wound dressing that restores normal wound healing rates by reducing free radicals in the wound, providing a native-like scaffold for the cells to divide and migrate, and enhancing vascularization in the wound. Another problem is the inability to monitor the wound in real time after the patient leaves the hospital, leading to digit or limb amputations. We will address this problem by developing a wireless system that can monitor the temperature and pH of the wound in real time, parameters that have been shown to be indicators of infection. Therefore, the overall goal of this proposal is to develop a shape- conforming antioxidant dressing that upon exposure to body temperature transforms into a gel that promotes new tissue formation in diabetic wounds and a feedback system that involves tissue conforming sensors to monitor bacterial infection and/or lack of healing. Toward this goal, we have developed a novel macromolecule - poly (polyethylene glycol citrate-co-N isopropyl acrylamide) - that incorporates a laminin-derived peptide. This material, referred to as PPCN-A5G81, supports tissue regeneration and can conform to the unique shape and depth of a wound. As for wireless monitoring of the wound, we pioneered the development of flexible, stretchable electronic sensors that can be integrated with human skin or implanted into the body for continuous, non-invasive health monitoring and treatment of disease. We hypothesize that: 1) incorporating immobilized Cu2+ into PPCN-A5G81 will confer vasculoinductive properties that significantly increase PPCN-A5G81’s ability to restore normal healing rates of full thickness dermal wounds in diabetic mouse and swine models; and 2) conforming temperature and pH sensors are safe and can remotely provide real time information regarding blood perfusion and infection in dermal wounds in diabetic animals. The specific aims of this proposal are to: 1) fabricate a PPCN-based regenerative dressing with vasculoinductive, dermoconductive, and dermoinductive properties and investigate its safety and efficacy for healing full thickness wounds in diabetic mice and diabetic pigs with metabolic syndrome; and 2) fabricate and characterize telemetric wound feedback tissue-conforming sensors capable of measuring temperature and pH in infected and non-infected diabetic dermal wounds. Results from this research will contribute to the development of innovative clinical products that reduce amputation rates and improve patient outcome.

摘要 糖尿病足溃疡(DFU)是糖尿病的主要并发症。这些溃疡，如果不治疗，可能会变成 感染并成为对患者健康的严重威胁。尽管伤口护理管理领域 尽管慢性DFU的有效治疗已经确立，但仍然是一项挑战。的主要目标是 DFU的治疗是为了伤口尽快愈合，并以持久的方式这样做。然而， 糖尿病创面的长期炎症、氧化组织损伤和血液循环障碍延迟了 伤口愈合过程，导致开放的、无法愈合的伤口，常常导致截肢。这项建议 将通过开发一种多功能伤口敷料来解决这些问题，这种敷料可以恢复正常的伤口愈合率 通过减少伤口中的自由基，为细胞分裂和迁移提供一个天然的支架，以及 增强伤口的血管生成。另一个问题是无法在术后实时监测伤口 病人离开医院，导致手指或肢体截肢。我们将通过开发 一种无线系统，可以实时监测伤口的温度和pH值，参数已经被 被证明是感染的指标。因此，这项建议的总体目标是发展一种形态-- 符合抗氧化剂的敷料，暴露在体温下会转化为凝胶 促进糖尿病创面的新组织形成和涉及组织的反馈系统 符合要求的传感器，用于监测细菌感染和/或愈合不足。为了实现这一目标，我们有 开发了一种新型的高分子-聚柠檬酸乙二醇酯-N-异丙基丙烯酰胺- 结合了层粘连蛋白衍生的多肽。这种材料被称为PPCN-A5G81，支持组织再生 并且可以符合伤口的独特形状和深度。至于伤口的无线监测，我们 率先开发出灵活的、可伸展的电子传感器，可以与人体皮肤或 植入体内，用于持续、非侵入性的健康监测和疾病治疗。我们假设 1)将固定化的Cu2+加入PPCN-A5G81中，可以显著地赋予血管诱导特性 提高PPCN-A5G81‘S修复糖尿病小鼠全层真皮创面正常愈合率的能力 和猪模型；2)符合标准的温度和pH传感器是安全的，可以远程提供实时 关于糖尿病动物皮肤伤口的血液灌流和感染的信息。的具体目标 该方案旨在：1)制备一种基于PPCN的具有血管诱导、皮肤传导、 和皮肤诱导特性，并研究其对糖尿病全层创面愈合的安全性和有效性 患有代谢综合征的小鼠和糖尿病猪；以及2)制作和表征遥测伤口反馈 能够测量感染和非感染糖尿病患者温度和pH的组织整合传感器 皮肤上的伤口。这项研究的结果将有助于开发创新的临床产品， 降低截肢率，改善患者预后。