Development of a Multi-Cue Biomaterial for Traumatic Tissue Injury

摘要生物材料具有巨大的应用潜力，但目前在材料的集成和自适应功能方面存在局限性。例如，创伤性损伤后会发生大量的事件和信号，包括用于与细胞和周围环境交流的电子、化学和物理信号，这些信号是当前材料无法复制的。因此，该项目旨在开发一种新型生物材料支架，该支架具有定制的化学、电和物理信号，可提供给损伤部位。电信号将由支架的运动提供，称为压电，或有针对性的“按需”超声波。这种可调谐的压电材料代表了一种飞跃，可以更好地再现生物材料的必要要求。这种多功能的压电生物材料将被制造出来，系统地表征，并发展成三维结构，用于未来的应用，如神经再生。这项研究将极大地帮助未来压电生物材料的发展和表征，特别是能够提供可定制信号的多功能材料。此外，这项工作旨在通过为辛辛那提当地高中生举办研讨会来扩大对科学的兴趣，学生将有机会学习压电和材料科学。总的来说，通过开发具有增强信号能力的强大生物材料，更好地复制原生环境，这类材料有可能彻底改变个性化医疗，并将无数未来的治疗方法从实验室带入临床。技术摘要能够向细胞和微环境传递所需信号以替代或修复损伤和疾病状态下的组织的新型生物材料的开发仍然具有挑战性。组织工程治疗、体外损伤和疾病模型以及细胞和组织的基础研究等各种应用都迫切需要一类新的多线索材料。为了解决更多相关材料的这一挑战，该项目将开发一种能够向细胞和微环境传递相关电、化学和物理信号的生物材料，以促进组织的再生和整合。为了实现这一目标，该研究项目将：1)电自旋一种对齐的、生物相容性的聚偏氟乙烯-共三氟乙烯（PVDF-TrFE）压电纳米纤维支架，该支架具有高表面积和孔隙度，具有组织特异性、脱细胞细胞外基质（ECM）的功能。2)在细胞和组织水平上定量确定机械变形引起的支架电势，并定量定位超声刺激，使支架响应机械变形产生电流，可按需应用。所产生的神经元和雪旺细胞对生物材料和电流的表型反应也将被检查。3)利用电纺丝PVDF-TrFE网状支架制造3D引导导管，解决神经损伤的创面修复问题，评估导管的力学性能和总压电性，同时保持导管与细胞的生物相容性。从长远来看，这项研究开发了一种变革性的生物材料，并提供了压电聚合物及其对细胞和组织影响的机械理解。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。

Non-Technical AbstractBiomaterials have immense potential for a countless number of applications, but limitations currently exist on the integration and adaptive functionality of the materials. For instance, there are a large number of events and signals that occur following a traumatic injury, including electrical, chemical, and physical signals that are used to communicate with cells and the surrounding environment that current materials are unable to replicate. Therefore, this project seeks to develop a novel biomaterial scaffold with customized chemical, electrical and physical signaling to be provided to the injury site. Electrical signaling will be provided by movement of the scaffold, called piezoelectricity, or by targeted “on-demand” ultrasound. This tunable, piezoelectric material represents a leap forward to materials that can better reproduce the requirements necessary of a biomaterial. The multi-functional, piezoelectric biomaterial will be fabricated, systematically characterized, and developed into a three-dimensional construct for future applications such as nerve regeneration. This study will greatly aid in the development and characterization of piezoelectric biomaterials for the future, and particularly multi-function materials capable of providing customizable signals. In addition, this work seeks to broaden interest in science by hosting a workshop for local Cincinnati high school students where students will have an opportunity to learn about piezoelectricity and material science. Overall, by developing robust biomaterials with enhanced signaling capabilities that better replicate the native environment, this class of material has the potential to revolutionize personalized medicine and deliver countless future therapies from the lab into the clinic.Technical AbstractNovel biomaterials capable of delivering the required signals to both cells and the microenvironment to replace or restore tissue in injury and disease states remain challenging to develop. A new class of multiple-cue material is greatly needed for a variety of applications including tissue engineered therapies, in vitro models of injury and disease, and fundamental studies of cell and tissue. To address this challenge for more relevant materials, this project will develop a biomaterial capable of delivering the relevant electrical, chemical, and physical signals to cells and the microenvironment to promote regeneration and integration of tissue. To accomplish this, the research project will: 1) Electrospin an aligned, biocompatible poly(vinylidene fluoride-co-trifluoroethylene)(PVDF-TrFE) piezoelectric, nanofiber scaffold with a high surface area and porosity that is functionalized with tissue-specific, decellularized extracellular matrix (ECM). 2) Quantitatively determine the electric potential of the scaffold resulting from mechanical deformation on the cellular and tissue level, in addition to quantification of location specific ultrasonic stimulation, which can be applied on demand as the scaffolds generate electric current in response to mechanical deformations. The resulting neuronal and Schwann cell phenotypic response to biomaterials and electric current produced will also be examined. 3) Utilize the electrospun PVDF-TrFE mesh scaffold to create 3D guidance conduits to address wound repair in nerve injury and assess the mechanics and total piezoelectricity of conduits while maintaining biocompatibility with cells. In the long-term, this research develops a transformative class of biomaterial and provides a mechanistic understanding of piezoelectric polymers and their effect on cells and tissue.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.