Development of a Multi-Cue Biomaterial for Traumatic Tissue Injury

非技术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适应性功能方面存在限制。例如，创伤后发生的大量事件和信号，包括用于与细胞和周围环境通信的电、化学和物理信号，这些都是目前的材料无法复制的。因此，本项目寻求开发一种新型的生物材料支架，该支架具有定制的化学、电气和物理信号，可提供给损伤部位。电信号将通过移动支架提供，称为压电性，或通过目标“按需”超声波。这种可调的压电材料代表着向能够更好地再现生物材料所需要求的材料的飞跃。这种多功能的、压电的生物材料将被制备、系统地表征，并发展成为未来神经再生等应用的三维结构。这项研究将极大地有助于未来压电生物材料的开发和表征，特别是能够提供可定制信号的多功能材料。此外，这项工作试图通过为辛辛那提当地的高中生举办一个研讨会来扩大人们对科学的兴趣，在那里学生将有机会学习压电性和材料科学。总体而言，通过开发具有增强信号功能的强大生物材料，更好地复制自然环境，这类材料有可能彻底改变个性化医学，并将无数未来的治疗方法从实验室应用到临床。技术摘要新型生物材料能够向细胞和微环境传递所需的信号，以替换或恢复处于损伤和疾病状态的组织，但开发起来仍然具有挑战性。在组织工程治疗、损伤和疾病的体外模型以及细胞和组织的基础研究等各种应用中，迫切需要一种新型的多线索材料。为了应对更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)电纺取向的生物相容性聚偏氟乙烯-三氟乙烯(PVDF-TrFE)压电纳米纤维支架，具有高比表面积和孔隙率，并使用组织特异性的脱细胞细胞外基质(ECM)功能化。2)定量测定支架在细胞和组织水平上由于机械变形而产生的电势，以及位置特定的超声刺激的量化，这可以根据需要应用，因为支架响应于机械变形而产生电流。由此产生的神经元和雪旺细胞对生物材料和产生的电流的表型反应也将被检测。3)利用电纺PVDF-TrFE网状支架构建3D引导导管，用于神经损伤的创面修复，并在保持与细胞生物相容性的同时评估导管的力学和总的压电性。从长远来看，这项研究开发了一类具有变革性的生物材料，并提供了对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NSF的法定使命，并通过使用基金会的智力优势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.