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

在美国，慢性伤口每年影响超过650万人，成本超过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会持续监测并及时有序地愈合伤口。然而，糖尿病、肥胖、循环不良、神经病变、移动困难或衰老的流行可能导致数月无法愈合的伤口。进一步的并发症，如特定的微生物聚生体可引起破坏性炎症，通常导致显著的发病率。为了有效地管理伤口，本研究开发了下一代伤口治疗，通过探索微针介导的伤口状态自适应（通过pH值水平）局部光疗，同时实现伤口愈合和抗菌效果。此后，我们将其称为针介导的自适应光疗或MAP伤口敷料。结合起来，MAP伤口敷料集成了自我诊断和自主治疗，可能会导致伤口愈合的转化解决方案。这项合作研究将整合科学发现和发现与教育场所指导研究生的研究，代（K-12至终身学习者），以及两所学院（堪萨斯州立大学和坦普尔大学）。该研究项目的核心是一种独特的原位光疗新方法，针头介导的自适应光疗（MAP）伤口敷料，独特地实现了纵向3D空间伤口传感和多功能pH敏感治疗，旨在实现物理组织愈合和致病细菌感染。中心假设是MAP可以自主地治疗慢性伤口，由伤口的状态控制（即，pH水平），而不需要任何电子设备或与医疗专业人员的互动。根据伤口的区域状态，MAP伤口敷料将微针定位在高细菌活性区域或急性伤口中。同时，MAP根据伤口状态改变其身体颜色，并将自然光转换为用于消毒的蓝光或用于加速组织再生的红光。光传递通过微针尖端发生，允许局部光疗。值得注意的是，MAP伤口敷料包括用于以下的导管：1）实现复杂3D结构微针的先进衍射显微光刻技术，其将充当具有先天透镜效应的光波导; 2）使用pH敏感性微图案化水凝胶和通过在水凝胶中注入pH染料的自适应滤光器的伤口状态驱动的自致动;和3）离体研究，以建立慢性伤口感测和治疗的临床前数据。因此，一种针对深层光穿透的新型伤口敷料，自适应波长转换PBM疗法可能是传统伤口敷料的上级替代品。该奖项反映了NSF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.