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

在美国，每年有超过650万人受到慢性伤口的影响，成本超过250亿美元，对公共医疗保健构成了重大风险。在健康的情况下，高效的天然宿主防御系统持续有序、及时地监测和愈合伤口。然而，糖尿病、肥胖、血液循环不良、神经病变、行动困难或衰老的流行可能会导致数月无法愈合的伤口。进一步的并发症，如特定的微生物群，可能会导致破坏性炎症，通常会导致严重的发病率。为了有效地管理伤口，本研究开发了新一代伤口治疗方法，通过探索微针介导的伤口状态适应性(通过pH水平)局部光疗，实现伤口愈合和抗菌效果的同时。从今以后，我们称其为微针介导的适应性光疗或MAP伤口敷料。结合起来，集自我诊断和自主治疗为一体的MAP伤口敷料可能会为伤口愈合带来一种翻译解决方案。这项合作研究将把科学发现和发现与教育场所相结合，为研究生提供研究指导、世代(K-12至终身学习者)和两个研究所(堪萨斯州立大学和坦普尔大学)的指导。这项研究项目的核心是一种独一无二的原位光疗的新方法，即微针介导的自适应光疗(MAP)创面敷料，它独特地实现了纵向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病理性细菌感染。中心假设是，MAP可以自主治疗慢性伤口，由伤口状态(即PH值水平)控制，不需要任何电子设备或与医疗专业人员互动。根据伤口的局部状态，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根据伤口状态改变其身体颜色，并将自然光转换为蓝色用于消毒或红光用于加速组织再生。光的传递通过微针的尖端进行，从而允许局部光疗。值得注意的是，MAP伤口敷料包括用于1)实现复杂3D结构微针的先进衍射微光刻技术，其将充当具有固有透镜效应的光波导；2)使用pH敏感微图案水凝胶的伤口状态驱动自驱动和通过在水凝胶中注入pH染料的自适应光学过滤器；以及3)体外研究，以建立用于慢性伤口传感和治疗的临床前数据。因此，一种针对深度光穿透的新型创面敷料，自适应波长转换PBM疗法可能是传统创面敷料的更好替代品。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.