Crystal Templated Polysaccharide Hydrogels

ID: MPS/DMR/BMAT(7623) 0805298 PI：施密特，克里斯汀ORG：德克萨斯大学奥斯汀分校标题：晶体模板多糖水凝胶智力优点：该提案的目标是设计生物材料，可以指导细胞的三维扩展治疗，以增强再生复杂的分支组织结构，如神经和血管网络。具体来说，PI建议开发和表征一种新的原位结晶方法，使用透明质酸（HA）和海藻酸多糖水凝胶在生物聚合物水凝胶中创建3D定向多孔网络，因为它们是公认的生物医学材料，具有模拟软组织（如神经）的机械性能。由于物理引导对细胞在发育和再生过程中的迁移至关重要，特别是对于复杂的神经元网络，因此需要控制这些凝胶的微观几何形状和孔隙度。初步的工作已经发现了一种完全独特的方法，这种方法也很容易和廉价，可以用相反的晶体网络形状来描绘生物聚合物水凝胶，从而在水凝胶中创建复杂的3D分支多孔结构。尿素被用来在水凝胶中生长晶体网络，从而获得非常复杂和精细的结构，这是任何其他方法都无法制造的。晶体生长延伸到整个水凝胶的体积，形成三维树突图案。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去除晶体。最终产物是一种生物聚合物水凝胶，含有类似于晶体网络的孔隙网络。该项目的具体目标是：(1)研究控制透明质酸和海藻酸盐水凝胶中图案的参数，探索各种晶体（即尿素、胍、磷酸二氢钾、甘氨酸）的使用，并研究浓度、粘度和表面活性剂对所得孔形态的影响。(2)开发方法来培养多个分离和独立的多孔网络，例如，可以模拟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络孔以促进细胞向内生长的方法，使这些水凝胶适应再生医学的应用。更广泛的影响：原位结晶创建连续的三维网络的水凝胶孔隙以前没有报道过。它代表了一种快速和廉价的方法，可以在生物聚合物水凝胶中创建微观结构，并且在各种组织工程应用中具有非常重要的意义，特别是在神经和血管组织的再生方面。该项目为研究生和本科生的跨学科培养提供了良好的平台。PI将与所有研究生和本科生在项目上进行一对一的工作。学生将被要求提供两周一次的项目报告，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的外展活动，特别是与德克萨斯大学的女性工程职业计划和少数民族工程介绍计划。

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.