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Patton – Rheology of Hydrogels Made with Healthy and COL3A1 Mutant Cell-Derived Matrix for vascular Ehlers-Danlos Syndrome

 

Rheology of Hydrogels Made with Healthy and COL3A1 Mutant Cell-Derived Matrix for vascular Ehlers-Danlos Syndrome (2024)

Undergraduates: Alexandra Patton, Elizabeth Doherty


Faculty Advisor: William Polacheck
Department: Biomedical Engineering

Hydrogels made with animal decellularized extracellular matrix (dECM) proteins have been used in microfluidic devices to investigate and model vasculature and associated diseases like vascular Ehlers-Danlos Syndrome. Using human dECM is limited by the availability of human tissue for research. Our lab has been making hydrogels using cell-derived matrix (CDM) as an in vitro model for human ECM. The mechanical properties of our CDM hydrogels remain under-characterized and thus preclude use as a tool to engineer the biophysical microenvironment. The mechanical properties of the CDM hydrogels can be manipulated by adding crosslinkers. We previously characterized CDM hydrogels with different crosslinkers using absorbance to determine the gelation kinetics. However, gelation kinetics cannot be related to the resultant mechanical properties of the hydrogel. Shear rheology is the gold standard in the literature to determine viscoelastic mechanical properties. In this study, we designed and implemented a rheological procedure to evaluate gelation and viscoelastic mechanical properties of CDM hydrogels with and without collagen crosslinkers. The hydrogels were made using CDM generated by healthy and vEDS patient-derived dermal fibroblasts. We determined the storage and loss moduli, defined the linear viscoelastic region, completed stress relaxation analysis, and compared strain stiffening properties between conditions by performing strain sweeps on the rheometer. Investigating the viscoelastic properties of CDM hydrogels with different formulations will provide clarity on whether the differences in mechanics associated with vEDS are maintained in the hydrogel state and inform future investigations into the utility of these gels for use within microfluidic vascular disease models.