Biophysical Characterization of Collagen based Hydrogels with the effect of Sulfated Glycosaminoglycans
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Date
2021-05
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The Ohio State University
Abstract
The extracellular matrix (ECM) enveloping cells in living tissue is comprised of signaling and structural support molecules. Two important types of ECM molecules are fibrillar collagen (e.g. type 1) and glycosaminoglycans (GAGs). The ECM is vital to maintenance of normal tissue as it controls cell signaling and is a semiporous barrier to interstitial fluid flow. In malignancies such as cancer, the composition of the ECM is significantly altered. For instance, cancer ECM contains elevated levels of negatively charged GAGs, which causes tissue to swell, alters the ECM architecture, and limits interstitial fluid transport. This thesis uses a microfluidic approach to characterize the effects of hyaluronic acid (HA) and chondroitin sulfate (CS), two GAGs that are known to be unusually abundant in certain solid tumors, on fluid transport (hydraulic permeability), and matrix microstructure (pore size, fiber radius and alignment). The study used 3 mg/ml collagen gels as the control ECM and modified the composition of the gels by adding CS (0.5, 1mg/ml) and CS (0.5, 1mg/ml) with HA (0.5, 1mg/ml). The results of the study demonstrate significant changes in the reconstituted ECM microstructure with the addition of the GAGs. Specifically, all trials have significantly increased the pore size and fiber radius in comparison to the control collagen gels, while alignment had no significant change. Although significant changes in ECM microarchitecture were observed, there were no significant changes in the hydraulic permeability of the gels. The results show how GAGs in collagen-based gels can significantly alter the physical structure of the ECM but has little effect on the transport properties. This study provides further evidence that GAGs play an important role in the physical properties of the ECM and suggests further studies should be conducted to better understand how to counteract the effects of GAGs in the tumor microenvironment.
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Keywords
Extra cellular Matrix, Characterization of Glycosaminoglycans