ATARI: A Terahertz tricorder for lAseR-assIsted wound healing

伤口愈合仍然是一个非常复杂的过程，减少愈合时间同时最大限度地减少组织疤痕是重要的医学目标。激光辅助伤口愈合是新兴的一个有吸引力的概念，在外科医学，保持无缝合线手术的承诺。最近，纳米粒子辅助的低剂量光热疗法引起了人们的关注，因为它们可以促进伤口愈合，同时需要更低的激光功率。然而，这些疗法仍处于起步阶段，尚未用于临床环境，因为由于激光吸收和伴随的热量产生导致温度迅速升高，可能导致严重的光热组织损伤。因此，尖端的诊断工具是必不可少的，以监测温度和减少损害。这个跨学科项目的目标是开发一种创新的技术，将纳米加热与一种由太赫兹辐射驱动的非侵入性/非电离诊断工具结合起来，这种技术可以在局部提供治疗以加速伤口愈合。与Swift Medical、Nanobrand和TeTechS这三家工业合作伙伴一起，我们将(i)研究纳米颗粒的功能化和设计，以改善纳米颗粒的热沉积和聚集/扩散的靶向性，以及组织内热点的产生；（ii）研究如何通过使用热敏键在纳米颗粒表面功能化药物来规避诸如过度血液凝固等竞争过程；（iii）开发一种智能实时太赫兹三维成像和温度传感系统，用于监测伤口愈合过程中的温度演变和光热损伤。这种平台将为角膜、神经和血管等脆弱组织的伤口愈合提供前所未有的方法。我们的发现将推动激光辅助再生纳米医学的基础研究，在临床环境中获得更强大的立足点，并有可能彻底改变与伤口和皮肤癌治疗相关的局部手术实践。由此产生的技术的商业化最终将使加拿大社会在自然/技术/卫生部门取得突破，并改善数百万加拿大人的健康。

Wound healing remains a very complex process and reducing healing time while minimizing tissue scarring are important medical goals. Laser-assisted wound healing is emerging as an appealing concept in surgical medicine, holding the promise of suture-less surgeries. Recently, nanoparticle-assisted low-dose photothermal therapies have garnered attention as they can facilitate wound healing while requiring lower laser power. However, these therapies are still in their infancy and have not been employed in the clinical setting since rapid elevation in temperature due to laser absorption and concomitant heat generation can cause significant photothermal tissue damage. Therefore, cutting-edge diagnostic tools are indispensable to monitor the temperature and minimize damage. The goal of this interdisciplinary project is to develop an innovative technique combining nanoheating, which locally delivers therapeutics to accelerate wound healing, with a non-invasive/non-ionizing diagnostic tool driven by terahertz radiation. Together with three industrial partners, Swift Medical, Nanobrand, and TeTechS, we will (i) study nanoparticle functionalization and design to improve targeting of heat deposition and clustering/diffusion of nanoparticles and the creation of hotspots within tissues; (ii) investigate how to circumvent competing processes such as excessive blood coagulation by functionalizing drugs on the nanoparticle surface using thermosensitive linkages; (iii) develop a smart real-time terahertz 3-D imaging and temperature sensing system for monitoring temperature evolution and photothermal damage during wound healing. Such a platform will offer an unprecedented method for wound healing of delicate tissues such as the cornea, nerves and blood vessels. Our discoveries will push forward fundamental research in laser-assisted regenerative nanomedicine to gain a stronger foothold within clinical settings and have the potential to revolutionize the topical surgical practices related to the treatment of wounds and skin cancers. The commercialization of the resulting technology will ultimately lead to breakthroughs for the Canadian society in nature/technology/health sectors and improve the health of millions of Canadians.