(722g) The In Vitro Cellular Response to Three-Dimensional Hyaluronic Acid Hydrogels Templated by Self-Assembled Poragen Architecture

Natural tissues boast a variety of patterns, porosities, and water contents to yield dynamic systems that regulate and support life enabling processes. When the function of these tissues goes awry, however, it is critical to implement biomedical technologies that are able to mimic the native environment and leverage their own intrinsic diversities in order to achieve sustained maintenance and replenish the native function. The wound healing process coordinates a complicated milieu of proteins, cells and other chemicals for the optimal recovery of the injured or diseased tissue. Thus, it is imperative that wound healing scaffolds combine both the chemical and physical attributes of the extracellular matrix to achieve the most desirable outcome.

Particularly in the area of nerve regeneration, there is a need for long range order to impart contact guidance for bridging large injury gaps. Current methods are not able to bridge large nerve injury gaps with efficacy to restore both motor and sensory function comparable to uninjured nerve. Three-dimensional hydrogel polymer matrices boasting internal alignment are an area of active research within tissue engineering.  Hyaluronic acid is a natural polymer intimately involved in the body’s wound healing process commonly employed for neural regenerative therapies. These typically amorphous hydrogels, however, do not provide any significant physical attributes beyond the inherent gel porosity and chemical regenerative support. To this end, the goal of this work is to fabricate three-dimensional biopolymer hydrogel matrices that leverage uniquely patterned crystalline networks.

A novel method of imposing an internal architecture through three-dimensional hydrogels uniquely yields both chemical and physical guidance in the injury site without the need for therapeutic additives. A colloidal crystal dissolved in the hydrogel solution either in excess of its thermal or miscibility limit allows for the formation of pores that are the negative imprint of the crystalline pattern. Restricting the hydrogel to the interstitial crystalline space is a novel method of imposing an internal architecture within three-dimensional gels to uniquely yield chemical and physical properties advantageous for a wide variety of applications. The bulk mechanical properties of these hydrogels have been characterized to demonstrate the extent to which the hydrogels are able to be modulated.

We hypothesize that by exploiting the ability to capture the negative imprint of poragen self-assembly within a hydrogel matrix, the resulting bulk material properties will promote preferential neurite extension along the path mapped by this structural template. Long range internal templating of these uniquely patterned liquid crystals is expected to improve the efficacy of regenerated neural processes. The ability to stabilize native, relevant architectures within hyaluronic acid gels yield a material can be optimized for peripheral nerve regeneration, vascular therapies and drug delivery.