Crystal Templated Polysaccharide Hydrogels

ID：MPS/dmr/bmat(7623)0805298 PI：Schmidt，Christine ORG：德克萨斯大学奥斯汀分校标题：晶体模板化多糖水凝胶内在优点：该提案的目标是设计能够引导细胞在三维方向延伸的生物材料，以促进神经和血管网络等复杂分支组织结构的再生。具体地说，PI建议开发和表征一种新的原位结晶方法，以使用透明质酸(HA)和海藻酸多糖水凝胶在生物聚合物水凝胶中创建3D取向的多孔网络，因为它们是公认的生物医学材料，具有模拟神经等软组织的机械性能。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，尤其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率。初步工作发现了一种完全独特的方法，该方法也是简单和廉价的，可以将生物聚合物水凝胶与晶体网络的形状相反，在水凝胶中创建复杂和错综复杂的3D分支多孔结构。尿素被用来在水凝胶中生长晶体网络，从而可以获得用任何其他方法都无法制造的非常复杂和精细的结构。晶体生长贯穿水凝胶的整个体积，形成3D树枝状图案。结晶后，生物聚合物被交联到晶体周围，以保持图案。用水冲洗水凝胶以溶解和去除晶体。最终产品是一种生物聚合物水凝胶，含有类似于晶体网络的孔网络。本项目的具体目标是：(1)研究控制HA和海藻酸盐水凝胶中图案形成的参数，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产生的孔形态的影响。(2)开发方法来培育多个独立和独立的多孔性网络，例如，可以模拟分支神经元和毛细血管的共同定位网络。(3)将这些水凝胶应用于再生医学，方法是用不同的生物分子和蛋白质来灌流和修饰网络毛孔，以促进细胞向内生长。BROADER影响：通过原位结晶来创建连续的3D水凝胶毛孔网络的研究尚未见报道。它代表了一种在生物聚合物水凝胶中创建微结构的快速且廉价的方法，并可能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一个极好的平台。PI将与所有研究生和本科生就该项目进行一对一的合作。学生将被要求每两周提交一次项目报告、手稿草稿，并在小组会议和会议上做口头陈述。国际工程协会和她的研究小组成员都将积极参加K-12的外联活动，特别是与德克萨斯大学妇女工程职业方案和少数族裔工程导论方案的活动。

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.