Investigating Laser-Activation of Structured Polymer Materials for Drug Delivery

PI 最近发现，某些聚合物的激光激活可以实现有效的货物运输。由于聚合物具有生物相容性、价格低廉且易于集成，该项目的工作计划利用这一最新的（出乎意料且尚未理解的）发现来制造和表征激光激活聚合物，目的是更好地为生物医学领域配备利用激光激活材料的新型体内货物输送方法。 在推进发现的同时，这项工作还将通过本科生和研究生的研究型教育，为未来多学科科学家和工程师的教育和培训做出贡献。通过 Mazur 集团与当地高中的合作、国家科学基金会资助的项目以及其研究小组中女性的高比例，他们将扩大代表性不足群体的参与。最后，利用该小组将外展和公共教育与研究相结合的完善计划，这项工作将广泛传播给公众。该项目旨在研究新发现的聚合物激光激活现象，着眼于开发结构灵活、有图案、可生物降解且易于植入体内的光激活聚合物材料，与传统的金属纳米制造基底不同，用于将有效负载输送到细胞中。该项目的目标是：1）研究这些聚合物材料和细胞的光与物质相互作用的基础物理； 2）开发和应用这些光活化聚合物材料用于生物医学工程应用。开发细胞治疗和再生医学的新方法以及研究修饰的基因表达，需要将遗传载体有效且安全地引入哺乳动物细胞中。生物医学需要高效、无毒并且可以在短时间内治疗大量细胞的基因递送方式。能够拥有高效的货物输送方法，同时保持细胞活力和医学相关的治疗吞吐量，将彻底改变纳米医学，并为新的细胞疗法和再生医学打开大门。总之，该项目重点研究由聚合物和生物塑料材料组成的各种结构的光与物质相互作用的基础物理及其在液体环境中的特性。其动机是创建一个灵活且生物相容的平台，用于可植入材料的转染。表征材料特性以确定这些材料对于不同敏感细胞类型的生物相容性和可行性非常重要。开发强大的设计和对新生物材料的理解将为利用光激活在患者体内以非侵入性方式触发输送开辟途径。由于该项目中使用的结构化聚合物表面易于制造且可扩展，因此在最大限度地提高临床应用的通量方面具有巨大的潜力。这项拟议的研究可能会对货物运输领域产生真正的变革，并为有源植入物提供巨大的机会。除了展示激光激活结构聚合物和生物塑料材料的货物输送及其在生物医学应用中的用途外，这项工作还将探索以下几个基本主题：（1）确定哪些效应控制成功的光-聚合物相互作用以实现细胞穿孔； (2) 通过实验测量表征不同类型的激光（脉冲和连续波）在结构化聚合物材料上激发时的压力波扰动和气泡形成； (3) 建立各种结构聚合物和生物塑料材料的设计指南； (4) 识别决定细胞与这些结构化材料有利附着的特性。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The PI recently discovered that laser-activation of certain polymers performs effective cargo delivery. As polymers are biocompatible, cheap, and easily integrated, the work in this project plans to leverage this recent (unexpected, and as-of-yet not understood) discovery to fabricate and characterize laser-activated polymers, with the aim of better equipping the biomedical field with novel in vivo cargo-delivery methods that harness laser-activated materials. While advancing discovery, the work will also contribute to the education and the training of future multidisciplinary scientists and engineers through research-based education of undergraduate and graduate students. Through the Mazur Group's work with local high schools, NSF sponsored programs, and the high representation of women in his research group, they will broaden participation of underrepresented groups. Finally, using the group's well-established program integrating outreach and public education with research, this work will be broadly disseminated to the general public.This project is for investigating the newly discovered phenomenon of laser-activation of polymers with an eye toward developing light-activated polymer materials that are flexible in structure, patterned, biodegradable, and easy to implant into the body, unlike traditional metallic nanofabricated substrates, for the delivery of payloads into cells. The goals of this project are to: 1) study the fundamental physics of the light-matter interactions of these polymer materials and cells; and 2) develop and apply these light-activated polymer materials for biomedical engineering applications. Developing new approaches for cell therapy and regenerative medicine, as well as studying modified gene expression, requires efficient and safe introduction of genetic vectors into mammalian cells. There is a biomedical need for gene delivery modalities that are efficient and non-toxic and that and can treat a large number of cells in a short amount of time. Being able to have a highly efficient cargo delivery method while maintaining cell viability and medically relevant treatment throughput would revolutionize nanomedicine and open the door to new cell therapies and regenerative medicine. In summary, this project focuses on studying the fundamental physics of light-matter interaction of various structures composed of polymer and bioplastic materials and properties in a liquid environment. The motivation is to create a flexible and biocompatible platform for transfection in implantable materials. It is important to characterize material properties to determine how biocompatible and viable these materials may be for different sensitive cell types. Developing a strong design and understanding of a new biomaterial will open avenues to trigger delivery in a non-invasive manner using light-activation within a patient. Due to the ease of fabrication and scalability of structured polymer surfaces to be used in this project, there is great potential to maximize throughput for clinical applications. This proposed research could be truly transformative to the field of cargo delivery and provide an enormous opportunity for active implants. Beyond demonstrating cargo delivery with laser-activated structured polymer and bioplastic materials and their use in biomedical applications, the work will also explore several fundamental topics as follows: (1) identifying what effects govern successful light-polymer interaction for cell poration; (2) characterizing the pressure wave perturbation and bubble formation, when excited with different types of laser (pulsed and continuous wave) on structured polymer materials through experimental measurements; (3) establishing guidelines for designing a wide variety of structured polymer and bioplastic materials; and (4) identifying properties that dictate favorable cell attachment to these structured materials.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.