(708b) Nano-Structured PEG-Heparin Hydrogel Characterization by High-Throughput Microrheology

Authors: 
Schultz, K. M., University od Delaware
Baldwin, A. D., University of Delaware
Campo-Deano, L., Katholieke Universiteit Leuven
Clasen, C., Katholieke Universiteit Leuven
Kiick, K. L., University of Delaware
Furst, E. M., University of Delaware


High-throughput screening of material properties of therapeutic hydrogelators enables the engineering of these materials for applications such as wound healing and tissue regeneration. Designing material to mimic biologically relevant environments, such as the extracellular matrix, requires knowledge of both the hydrogelation reaction and the final material assembly conditions over a large composition space. Recently developed covalently cross-linked dithiol poly(ethylene glycol)-maleimide functionalized high molecular weight heparin (PEG-HMWH) hydrogels are of particular interest due to heparin's ability to sequester and stabilize soluble proteins, such as growth factors. Multiple particle tracking microrheology is used to measure the structure and rheological properties of the material. In this technique, probe particles are embedded into the precursor solution, the Brownian motion of the particles is tracked and rheological properties are directly calculated from the probes mean-squared displacement. The hydrogelation kinetics is monitored as the material evolves with time, allowing the critical gelation time and critical relaxation exponent to be determined as a function of cross-linker size. The final material properties are screened using high-throughput microrheology, a technique that couples a microfluidic device and microrheological measurements, over a parameter space that includes the total polymer concentration, cross-linker molecular weight and number of available cross-linkable sites on the heparin or backbone functionality. Gelation state diagrams are created and the area where a cross-linked hydrogel forms, the gelation envelope, is measured for each size of cross-linker and backbone functionality. The borders of the gelation envelope are modeled using Flory-Stockmayer theory. These gelation diagrams enable the composition of the hydrogel with the precise rheological properties suitable for processing this polymeric hydrogel, specifically using electrospinning, to be determined. Electrospinning is an increasingly important polymer processing method for generating nano- and micro-structured biomimetic materials. Electrospun PEG-HMWH hydrogel fibers present the proper chemistry that can deliver soluble growth factors and present non-soluble adhesion and cleavage epitopes that can be engineered to mimic the biochemical and biophysical cues of the native extracellular matrix to elicit cell growth and proliferation.

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