Crystal Templated Polysaccharide Hydrogels

ID：MPS/DMR/BMAT（7623）0805298 PI：施密特，克莉丝汀 ORG：德克萨斯大学奥斯汀分校晶体模板多糖水凝胶智力优势：该提案的目标是设计生物材料，可以引导细胞在三维中延伸，用于治疗，以增强复杂分支组织结构（如神经和血管网络）的再生。 具体而言，PI建议开发和表征一种新型原位结晶方法，以使用透明质酸（HA）和藻酸盐多糖水凝胶在生物聚合物水凝胶中创建3D定向多孔网络，因为它们是成熟的生物医学材料，具有模拟软组织（如神经）的机械性能。 期望控制这些凝胶的微观几何形状和孔隙率，因为物理引导对于细胞在发育和再生期间的迁移是至关重要的，特别是对于复杂的神经元网络。 初步工作已经发现了一种完全独特的方法，该方法也很容易和便宜，可以用晶体网络的相反形状来图案化生物聚合物水凝胶，以在水凝胶中创建复杂和错综复杂的3D分支多孔结构。尿素用于在水凝胶内生长结晶网络，允许获得无法通过任何其他方法制造的非常复杂和精细的结构。晶体生长在整个水凝胶体积中延伸，产生3D树枝状图案。结晶后，生物聚合物在晶体周围交联以保持图案。用水冲洗水凝胶以溶解并除去晶体。最终产物是含有类似于晶体网络的孔网络的生物聚合物水凝胶。该项目的具体目的是：（1）研究控制HA和藻酸盐水凝胶中图案化的参数，探索各种晶体的使用（即，尿素、胍、磷酸二氢钾、甘氨酸），并研究浓度、粘度和表面活性剂对所得孔形态的影响。(2)开发方法来生长多个单独和独立的多孔网络，例如，可以模仿分支神经元和毛细血管的共定位网络。(3)通过开发各种生物分子和蛋白质灌注和修饰网状孔以促进细胞向内生长的方法，使这些水凝胶适用于再生医学应用。更广泛的重要性：原位结晶以创建连续的3D水凝胶孔网络以前尚未报道。 它代表了在生物聚合物水凝胶内产生微结构的快速且廉价的方法，并且在各种组织工程应用中可能具有非常重要的意义，特别是对于神经和血管组织的再生。 该项目为研究生和本科生的跨学科培训提供了一个很好的平台。 PI将与所有研究生和本科生一对一地进行项目。 学生将被要求提供双周项目报告，草稿，并在小组会议和会议上做口头报告。 PI和她的研究小组成员都将积极参与K-12外展活动，包括，特别是，与得克萨斯大学的职业生涯在工程妇女计划和少数民族介绍工程计划。

ID: MPS/DMR/BMAT(7623) 0805298 PI: Schmidt, Christine ORG: University of Texas-AustinTitle: Crystal Templated Polysaccharide HydrogelsINTELLECTUAL MERIT: The goal of the proposal is to engineer biomaterials that can guide the extension of cells in three dimensions for therapies to enhance regeneration of complex branched tissue structures such as nerve and vascular networks. Specifically, the PI proposes to develop and characterize a novel in situ crystallization method to create 3D oriented porous networks in biopolymer hydrogels using hyaluronic acid (HA) and alginate polysaccharide hydrogels because they are well-established biomedical materials that have mechanical properties that mimic soft tissues such as nerve. It is desired to control the microgeometry and porosity of these gels since physical guidance is critical for migration of cells during development and regeneration, particularly for intricate neuron networks. Preliminary work has discovered a completely unique method, which is also easy and inexpensive, to pattern biopolymer hydrogels with the inverse shape of crystal networks to create complex and intricate 3D branched porous structures in hydrogels. Urea is used to grow a crystalline network within a hydrogel, permitting very intricate and fine structures to be obtained that cannot be fabricated by any other method. Crystal growth extends throughout the volume of the hydrogel creating 3D dendritic patterns. After crystallization, the biopolymer is crosslinked around the crystals to preserve the pattern. The hydrogel is rinsed with water to dissolve and remove the crystals. The end product is a biopolymer hydrogel containing a network of pores resembling the crystal network. The Specific Aims of this project are: (1) Study the parameters that control patterning in HA and alginate hydrogels exploring the use of various crystals (i.e., urea, guanidine, potassium dihydrogen phosphate, glycine) and study the effect of concentration, viscosity, and surfactants on the resulting pore morphologies. (2) Develop methods to grow multiple separate and independent porous networks that, for example, could mimic co-localized networks of branched neurons and capillaries. (3) Adapt these hydrogels for regenerative medicine applications by developing methods to perfuse and modify the networked pores with various biomolecules and proteins to promote cell ingrowth.BROADER IMPACTS: In situ crystallization to create continuous 3D networks of hydrogel pores has not previously been reported. It represents a quick and inexpensive approach to create microstructure within biopolymer hydrogels and could have very important implications in a variety of tissue engineering applications, especially for regeneration of nerve and vascular tissues. The project provides an excellent platform for interdisciplinary training of graduate and undergraduate students. The PI will work one-on-one with all graduate and undergraduate students on the project. Students will be expected to provide bi-weekly project reports, draft manuscripts, and make oral presentations at group meetings and at conferences. The PI and her research group members will all participate actively in K-12 outreach activities, including, in particular, with the University of Texas Careers in Engineering for Women program and the Minority Introduction to Engineering program.