Multifunctional Intelligent Hierarchical Fibrous Biomaterials Integrated with Multimodal Biosensing and Feedback-Based Interventions for Healing Infected Chronic Wounds

多功能智能分层纤维生物材料与多模式生物传感和基于反馈的干预措施相结合，用于治愈感染的慢性伤口

• 批准号: 10861531
• 负责人: Jingwei Xie
• 金额: $ 77.67万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-20 至 2024-08-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10861531
• 关键词: Acceleration; Address; Affect; Aging; Amputation; Antibiotics; Biocompatible Materials; Biometry; Biosensing Techniques; Biosensor; Blood capillaries; Bone Regeneration; COVID-19; Cellular Phone; Clinic; Clinical; Collaborations; Complications of Diabetes Mellitus; Data; Development; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic mouse; Disease; Drug Delivery Systems; Electrospinning; Electrostatics; Epithelium; Evaluation; Failure; Feedback; Fiber; Foot Ulcer; Foundations; Functional disorder; Granulation Tissue; Growth Factor; Health Care Costs; Healthcare; Heart Diseases; Home; Hospitals; Human; In Situ; Individual; Infection; Inflammation; Intelligence; Intervention; Iontophoresis; Leg Ulcer; Light; Lower Extremity; Measurement; Mechanics; Medical; Methods; Microbial Biofilms; Modality; Monitor; Nerve Regeneration; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Porosity; Procedures; Process; Pseudomonas aeruginosa; Quality of life; Radial; Reproducibility; Research; Risk; Skin; Staphylococcus aureus; Streptococcus; Structure; System; Tablet Computer; Telemedicine; Temperature; Testing; Time; Type 2 diabetic; United States; Uric Acid; Venous; Visit; Wound Infection; Wound models; bioelectronics; bioscaffold; chronic wound; combat; combat wound; cost; data acquisition; data exchange; decubitus ulcer; design; diabetic; diabetic patient; digital; effective therapy; efficacy evaluation; experience; fabrication; flexibility; handheld mobile device; healing; hydrophilicity; improved; in vivo; infection management; innovation; mortality; multimodality; nanofiber; novel; pathogen; pharmacologic; portability; prevent; printed circuit board; real time monitoring; sensor; skin wound; smart bandage; success; tissue regeneration; wireless; wound; wound care; wound closure; wound healing; wound treatment

Project Summary Chronic wounds arise as a consequence of diabetes, venous dysfunction, aging, surgeries or others and pose a major healthcare challenge in the United States. For example, 20-25% of diabetic patients develop foot ulcers (a type of chronic wounds) and about 63.4% of them develop infections. Failure to prevent or manage infections results in high healthcare cost, amputations, and an increased mortality. Despite recent progress in wound care, the effective treatment of infected chronic wounds remains challenging. One problem is the lack of biomaterial scaffolds that can simultaneously combat wound infection and promote wound tissue regeneration. The other problem is the inability to monitor the wound in real time and offer feedback-based, pharmacological interventions. Also, frequent hospital visits associated with existing methods increase the patient's exposure risk to contagious diseases (e.g., COVID-19). Thus, there is an urgent need to develop new telemedicine therapies for home-based, effective treatment of infected chronic wounds. The objective of this project is to develop intelligent hierarchical fibrous biomaterials, consisting of vertically aligned microfibers on the bottom (promoting granulation tissue for- mation), radially aligned nanofibers on the top (accelerating re-epithelialization), and multimodal bioelectronics integrated on nanofibers (monitoring the wound status and providing iontophoresis-controlled multiple drug de- livery), to treat infected chronic wounds. The central hypothesis is judiciously designed hierarchical fibrous bio- materials, together with on-demand multistage pharmacological interventions guided by real-time wound moni- toring, can effectively combat infections/biofilms and promote wound healing. Two specific aims include (1) fab- ricating and characterizing intelligent biomaterials and (2) evaluating efficacy of intelligent biomaterials in moni- toring wound status, combating infections and promoting wound healing using diabetic mice wounds and ex vivo human skin wounds. The proposed intelligent biomaterial is innovative as compared to existing smart dressings in light of its biodegradable hierarchical fibrous biomaterial that can promote wound tissue regeneration, its inte- grated multimodal bioelectronics capable of providing comprehensive information of wound status and offering feedback-based, multistage delivery of antibiotics and growth factors, and in vivo and ex vivo evaluations using both diabetic mice wounds and human skin explants to identify existing issues and accordingly improve designs and fabrications. Also, the correlations of the wound status/healing, sensor readouts and delivered drug amounts will be established in this research, which are still lacking. The research team's complementary expertise, past collaboration experiences and collaboratively generated preliminary results form the basis for the success of this project. Results from this project will contribute to development of translational telemedicine products that can improve the efficacy of chronic wound care, decrease healthcare costs, and most importantly reduce the rates of amputation and modality and improve quality of life of patients, which can also lay foundations for development of other closed-loop biomedical systems for treating heart diseases and promoting bone and neural regeneration.

项目概要 慢性伤口是由糖尿病、静脉功能障碍、衰老、手术或其他原因引起的，并构成 美国的一个重大医疗保健挑战。例如，20-25%的糖尿病患者会出现足部溃疡 （一种慢性伤口），其中约 63.4% 会出现感染。未能预防或控制感染 导致高昂的医疗费用、截肢和死亡率增加。尽管伤口护理最近取得了进展， 有效治疗感染的慢性伤口仍然具有挑战性。问题之一是缺乏生物材料 可以同时对抗伤口感染并促进伤口组织再生的支架。另一个 问题是无法实时监测伤口并提供基于反馈的药物干预措施。 此外，与现有方法相关的频繁去医院就诊增加了患者接触传染性病毒的风险 疾病（例如，COVID-19）。因此，迫切需要开发新的远程医疗疗法，用于家庭、 有效治疗感染的慢性伤口。该项目的目标是开发智能分层 纤维生物材料，由底部垂直排列的微纤维组成（促进肉芽组织- 化）、顶部径向排列的纳米纤维（加速上皮化）和多模式生物电子学 集成在纳米纤维上（监测伤口状态并提供离子电渗控制的多重药物去除 制服），治疗感染的慢性伤口。中心假设是明智设计的分层纤维生物 材料，以及实时伤口监测指导下的按需多阶段药物干预 撕裂，可以有效对抗感染/生物膜并促进伤口愈合。两个具体目标包括（1）晶圆厂 智能生物材料的表征和表征，以及（2）评估智能生物材料在监测中的功效 使用糖尿病小鼠伤口和离体来破坏伤口状态，对抗感染并促进伤口愈合 人类皮肤伤口。与现有的智能敷料相比，所提出的智能生物材料具有创新性 鉴于其可生物降解的分级纤维生物材料可以促进伤口组织再生，其集成 光栅多模态生物电子学能够提供伤口状态和治疗的全面信息 基于反馈的抗生素和生长因子的多阶段递送，以及体内和离体评估 糖尿病小鼠伤口和人类皮肤外植体，以识别现有问题并相应改进设计 和捏造。此外，伤口状态/愈合、传感器读数和输送药物量的相关性 本研究将建立这一点，目前尚缺乏。研究团队的互补专业知识，过去 合作经验和合作产生的初步成果构成了本次成功的基础 项目。该项目的结果将有助于开发可转化的远程医疗产品 提高慢性伤口护理的功效，降低医疗成本，最重要的是降低发病率 截肢和模态的改善，提高患者的生活质量，也可以为发展奠定基础 用于治疗心脏病和促进骨骼和神经再生的其他闭环生物医学系统。