Collaborative Research: Microneedle-mediated Adaptive Phototherapy (MAP) for Wound Healing

在美国，慢性伤口每年影响650多万人，费用超过250亿美元，对公共医疗保健构成重大风险。在健康的情况下，一个高效的先天宿主防御系统持续监测并以有序和及时的方式愈合伤口。然而，糖尿病、肥胖、血液循环不良、神经病变、活动困难或衰老的流行可能导致伤口在几个月内无法愈合。进一步的并发症，如特定的微生物联合体可引起破坏性炎症，往往导致显著的发病率。为了有效地管理伤口，本研究通过探索微针介导、伤口状态适应性（通过pH水平）、局部光疗，开发了下一代伤口治疗方法，使伤口愈合和抗菌效果同时发生。因此，我们称之为微针介导的适应性光疗或MAP伤口敷料。将自我诊断和自主治疗相结合的MAP伤口敷料可能会为伤口愈合提供一种转化解决方案。这项合作研究将把科学发现和发现与教育场所结合起来，指导研究生进行研究，几代人（K-12到终身学习者），以及两个研究所（堪萨斯州立大学和天普大学）。该研究项目的核心是一种独一无二的原位光疗新方法，微针介导的适应性光疗（MAP）伤口敷料，独特地实现纵向3D空间伤口传感和多功能ph敏感治疗，旨在物理组织愈合和致病性细菌感染。核心假设是，MAP可以自主治疗慢性伤口，由伤口状态（即pH值）控制，而不需要任何电子设备或与医疗专业人员互动。根据伤口的区域状态，MAP伤口敷料将微针放置在细菌高度活跃的区域或急性伤口。同时，MAP会根据伤口状态改变自身颜色，并将自然光转换成用于消毒的蓝色或加速组织再生的红色。光通过微针的尖端传递，从而实现局部光疗。值得注意的是，MAP伤口敷料包括用于1)先进的衍射微光刻技术的导管，该技术可实现复杂的3D结构微针，该微针将充当具有固有透镜效应的光波导；2)通过在水凝胶中注入pH染料，利用pH敏感微图水凝胶和自适应滤光片实现伤口状态驱动自驱动；3)体外实验，建立慢性伤口传感和治疗的临床前数据。因此，一种针对深光穿透的新型创面敷料——自适应波长转换PBM疗法有望成为传统创面敷料的优良替代品。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Chronic wounds impact over 6.5 million individuals in the United States annually, and the costs exceed $25 billion, posing a significant risk in public healthcare. In healthy conditions, a highly efficient innate host defense system continually monitors and heals the wounds in an orderly and timely manner. However, the prevalence of diabetes, obesity, poor circulation, neuropathy, difficulty in moving, or aging can cause wounds unresolvable for several months. Further complications such as a particular microbial consortium can cause destructive inflammation, often resulting in significant morbidity. To effectively manage the wound, this research develops the next-generation wound treatment that enables simultaneous wound healing and antimicrobial effects by exploring a microneedle-mediated, wound state adaptive (via pH level), localized phototherapy. We henceforth call it a Microneedle-mediated Adaptive Phototherapy or MAP wound dressing. Combined, the MAP wound dressing that integrates self-diagnosis and autonomous treatment may lead to a translational solution for wound healing. This collaborative research will integrate the scientific findings and discoveries with educational venues for mentoring graduate students in research, generations (K-12 to lifelong learners), and two institutes (Kansas State University and Temple University).Central to this research project is a new approach of a one-of-a-kind in-situ phototherapy, Microneedle-mediated Adaptive Phototherapy (MAP) wound dressing that uniquely enables longitudinal 3D spatial wound sensing and multifunctional pH-sensitive treatment, aiming at physical tissue healing and pathogenetic bacterial infections. The central hypothesis is that the MAP can autonomously treat chronic wounds, controlled by the state of the wound (i.e., pH level), without the need for any electronics or interaction with medical professionals. Depending on the regional state of the wound, the MAP wound dressing positions the microneedles either in the highly bacterial active region or the acute wounds. Simultaneously, the MAP changes its body color depending on the wound state and converts the natural light into blue for sanitizing or red light for accelerating tissue regeneration. The light delivery occurs through microneedles tips, allowing localized phototherapy. Notably, the MAP wound dressing includes conduits for 1) the advanced diffraction microlithography technique that realizes complex 3D structured microneedles, which will act as an optical waveguide with an innate lens effect; 2) the wound state-driven self-actuation using pH-sensitive micropatterned hydrogel and adaptive optical filter by infusing pH dye in the hydrogel; and 3) ex vivo studies to build preclinical data for chronic wound sensing and treatments. Therefore, a novel wound dressing aimed at deep light penetrating, the adaptive wavelength converting PBM therapy could be a superior substitute for conventional wound dressing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.