Chemically defined, plant-derived biomaterial platform for human cell culture

用于人类细胞培养的化学成分明确的植物源生物材料平台

• 批准号: 2207275
• 负责人: Padma Gopalan
• 金额: $ 56.49万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2207275&HistoricalAwards=false
• 关键词: Chemically; defined; plant; derived; biomaterial

NON-TECHNICAL SUMMARYStem cells are cells within our bodies that unlike most cells, have the potential to differentiate into many different types of cells. Stem cells have been an area of focused study in basic sciences due to their therapeutic potential in treating human disease. However, precise control over stem cell differentiation into useful therapeutic cells remains challenging, and better regulation of stem cell behaviors such as adhesion, proliferation, differentiation, and tissue formation could expedite biomedical applications of human stem cells. Natural and synthetic biomaterials can serve as a “scaffold” that controls the cell’s environment, often by mimicking the native environment in which the cells grow. Plants have developed unique and diverse material properties over more than 700 million years of evolution, and plant properties are ideally suited to support stem cell growth. The scalable, sustainable nature of plant leaf production, along with enhanced oxygen diffusion, wide diversity of morphology and length scales, and their biocompatibility, all make a strong case for their development as a broadly useful biomaterial for human stem cell manufacturing. However, plant-derived materials provide no intrinsic mechanism for proper attachment and function of human cells. The synthetic polymer coatings developed through this work will control cell-biomaterial attachment and present signals to stem cells that control their fate. The plant-derived biomaterials developed through this work can be delivered to cell biologists and bioengineers, who can use them to probe key biological questions or manufacture specific cells of interest. This research program will serve to educate and inspire rural high school students and teachers by the development of an interdisciplinary learning module. The award will enhance, retain, and promote engagement with underrepresented groups, through the Women in Science & Engineering Leadership Institute, and research experience for undergraduates at UW-Madison. TECHNICAL SUMMARYBiomaterials based on decellularized plant materials provide intricate interconnected vasculature for transport of biomolecules, as well as wide diversity in morphology and length scales for cell alignment and pattern registration. The research proposed here aims to develop a decellularized plant leaf-based biomaterial as a broadly useful and adaptable biomaterial for human cell culture. The research will test the hypothesis that plant-derived materials conformally coated with chemically-defined polymer films will support cell adhesion, viability and alignment, and also enhance stem cell differentiation toward functional tenocytes and myocytes. The work focuses on developing methodology to fully characterize plant-derived biomaterials and on developing coating chemistry to modify leaf surfaces to make them conducive for human cell culture. This understanding will allow systematic interrogation of the effect of surface topography and the customizable surface chemistry on the cellular alignment and differentiation. The expected outcomes of the proposed research are 1) the development of the decellularization process, and comprehensive characterization of chemical composition, cytotoxicity, morphology, enzymatic degradability, mass transport, and mechanical properties of the leaf material, 2) development of novel copolymer coating chemistry to minimize non-specific adsorption of biomolecules, enable the nanometer-scale co-localization of adhesion peptides, and quantitatively present a combination of muscle and tendon extra-cellular matrix derived peptides, and 3) correlating the leaf microtopography and surface chemistry with cell alignment during myogenic and tenogenic differentiation using second harmonic generation microscopy.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.

非技术摘要干细胞是我们体内的细胞，与大多数细胞不同，干细胞由于其在治疗人类疾病方面的治疗潜力而成为基础科学的重点研究领域。 ，精确控制干细胞分化为有用的治疗细胞仍然具有挑战性，更好地调节干细胞行为（例如粘附、增殖、分化和组织形成）可以加速人类干细胞的生物医学应用。控制细胞环境的“支架”，通常是通过模仿细胞生长的原生环境。经过 7 亿多年的进化，植物已经形成了独特且多样化的材料特性，而植物特性非常适合支持干细胞的生长。植物叶子生产的可扩展性、可持续性质，以及增强的氧扩散、形态和长度尺度的广泛多样性以及它们的生物相容性，都为它们作为人类干细胞制造的广泛有用的生物材料的发展提供了强有力的理由。 -衍生材料通过这项工作开发的合成聚合物涂层没有提供人体细胞正确附着和功能的内在机制，它将控制细胞-生物材料的附着，并向干细胞发出控制其命运的信号。细胞生物学家和生物工程师，他们可以利用它们来探索关键的生物学问题或制造感兴趣的特定细胞。该研究计划将通过开发跨学科学习模块来教育和激励农村高中学生和教师。 、保留并促进参与技术概要基于脱细胞植物材料的生物材料为生物分子的运输提供了复杂的互连脉管系统，并在形态和长度尺度上具有广泛的多样性。这里提出的研究旨在开发一种基于脱细胞的植物叶的生物材料，作为人类细胞培养的广泛用途和适应性的生物材料。假设涂有化学成分聚合物薄膜的植物源材料将支持细胞粘附、活力和排列，并增强干细胞向功能性肌腱细胞和肌细胞的分化。这项工作的重点是开发充分表征植物源生物材料的方法。开发涂层化学来修饰叶子表面，使其有利于人类细胞培养，这一理解将允许系统地研究表面形貌和可定制的表面化学对细胞排列和分化的影响。拟议研究的预期结果是1)。这脱细胞工艺的发展，以及叶材料的化学成分、细胞毒性、形态、酶降解性、传质和机械性能的综合表征，2) 开发新型共聚物涂层化学，以最大限度地减少生物分子的非特异性吸附，使粘附肽的纳米级共定位，并定量呈现肌肉和肌腱细胞外基质衍生肽的组合，以及 3) 将叶子微形貌和表面化学与使用二次谐波发生显微镜在肌原和肌腱分化过程中进行细胞排列。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。