INTELLECTUAL 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.
