Investigating Laser-Activation of Structured Polymer Materials for Drug Delivery

PI最近发现，激光激活某些聚合物可以有效地运送货物。由于聚合物具有生物相容性，廉价且易于集成，因此该项目计划利用这一最新发现（出乎意料，并且尚未被理解）来制造和表征激光活化聚合物，目的是更好地装备生物医学领域，利用激光活化材料的新型体内货物输送方法。在推进发现的同时，这项工作也将通过对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，NSF赞助的项目，以及他的研究小组中女性的高代表性，他们将扩大代表性不足的群体的参与。最后，利用该组织完善的项目，将外展和公众教育与研究结合起来，这项工作将广泛传播给公众。这个项目是为了研究新发现的聚合物激光激活现象，着眼于开发光激活聚合物材料，这种材料结构灵活，有图案，可生物降解，易于植入体内，不像传统的金属纳米制造基质，用于将有效载荷输送到细胞中。该项目的目标是：1)研究这些聚合物材料和细胞的光-物质相互作用的基本物理学；2)开发和应用这些光活化高分子材料用于生物医学工程。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，需要有效和安全地将遗传载体引入哺乳动物细胞。生物医学需要高效、无毒、能在短时间内治疗大量细胞的基因传递方式。能够在保持细胞活力和医学相关治疗吞吐量的同时拥有高效的货物输送方法，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。综上所述，本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物质相互作用的基本物理及其在液体环境中的性能。其动机是为植入材料的转染创造一个灵活和生物相容性的平台。表征材料特性以确定这些材料对不同敏感细胞类型的生物相容性和可行性是很重要的。对一种新的生物材料进行强有力的设计和理解，将为在患者体内使用光激活以非侵入性方式触发递送开辟道路。由于该项目中使用的结构聚合物表面易于制造和可扩展性，因此具有最大限度地提高临床应用吞吐量的巨大潜力。这项提议的研究可能会真正改变货物运输领域，并为主动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运输及其在生物医学应用中的应用之外，这项工作还将探索以下几个基本主题：(1)确定成功的光聚合物相互作用对细胞穿孔的影响；(2)通过实验测量，表征了不同类型激光（脉冲波和连续波）对结构高分子材料的压力波扰动和气泡形成；(3)建立设计各种结构聚合物和生物塑料材料的指导方针；(4)确定有利于细胞附着于这些结构材料的特性。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。

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.