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

项目摘要 慢性伤口是糖尿病、静脉功能障碍、衰老、手术或其他原因造成的。 这是美国医疗保健领域的一大挑战。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%会发生感染。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。尽管最近在伤口护理方面取得了进展， 慢性感染创面的有效治疗仍然具有挑战性。其中一个问题是缺乏生物材料 可同时对抗伤口感染和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理学干预。 此外，与现有方法相关的频繁就诊增加了患者接触传染性疾病的风险 疾病(例如，新冠肺炎)。因此，迫切需要开发新的基于家庭的远程医疗疗法， 慢性感染创面的有效治疗。本项目的目标是开发智能分层 纤维状生物材料，由底部垂直排列的微纤维组成(促进肉芽组织- )、顶部的径向排列的纳米纤维(加速再上皮化)和多模式生物电子学 集成在纳米纤维上(监控伤口状态并提供离子导入控制的多种药物去除 用于治疗感染的慢性伤口。中心假设是精心设计的分层纤维生物- 材料，以及在实时创伤监测指导下的按需多阶段药物干预。 托林，可以有效地对抗感染/生物膜，促进伤口愈合。两个具体目标包括(1)制造- 丰富和表征智能生物材料；(2)智能生物材料的药效评价。 利用糖尿病小鼠创面和体外实验研究创面状态、抗感染和促进创面愈合 人类皮肤上的伤口。与现有的智能敷料相比，提出的智能生物材料是创新的。 鉴于其可生物降解的层次化纤维生物材料可促进创面组织再生，其在生物医学领域的应用前景广阔。 可提供伤口状态和提供全面信息的栅格多模式生物电子设备 基于反馈的多阶段给予抗生素和生长因子，以及使用 糖尿病小鼠伤口和人类皮肤移植，以确定存在的问题并相应地改进设计 和捏造。此外，伤口状态/愈合、传感器读数和给药量之间的相关性 将在本研究中确立，这还是欠缺的。研究团队的互补专业知识，过去 协作经验和协作生成的初步结果构成了此次成功的基础 项目。该项目的成果将有助于开发可翻译的远程医疗产品， 提高慢性伤口护理的疗效，降低医疗成本，最重要的是降低死亡率 截肢和矫形，改善患者的生活质量，这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。

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.