Twisha
Tirumani Shivashankar

Tuning Matrix Degradability using Hydrogel Composites to Modulate Angiogenesis STEM

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Twisha Tirumani Shivashankar

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Functional vasculature is essential for tissue survival, making angiogenesis, the formation of new blood vessels from existing ones, a key aspect of tissue engineering. To support this process, biomaterials must replicate features of the native extracellular matrix to promote cell growth and organization. Among these, matrix degradability plays a major role by regulating vascular sprouting and 3D cell migration. Norbornene-modified hyaluronic acid (NorHA) hydrogels are widely used for their biocompatibility and tunable crosslinking. However, conventional NorHA is non-degradable, limiting cell spreading and vessel formation. While enzymatically cleavable crosslinkers allow cell-mediated degradation, they offer limited external control over matrix remodeling. To address this, our lab developed degradable NorHA hydrogels by chemically modifying hyaluronic acid through oxidation with sodium periodate and esterification with carbic anhydride. This produced two variants: NorHA-20%Ox and NorHACA-20%Ox, which degrade over 14 and 2 days, respectively, in microgel studies. However, they lack mechanical strength, and their angiogenic potential in bulk systems remains unexplored. This project develops composite hydrogels by blending degradable and non-degradable NorHA in ratios from 95:5 to 50:50. Compression testing showed Young's moduli ranging from 16.23 to 20.66 kPa in NorHA- NorHACA 20%Ox composites. Bulk degradation was also evaluated over time. Cell-matrix interactions were studied by encapsulating GFP-tagged NIH3T3 fibroblasts, while HUVEC-MSC spheroids were embedded to assess angiogenic sprouting. Fibroblasts appeared larger and showed minute extensions in composites with higher degradable content. This project aims to optimize the balance between mechanical integrity and angiogenic potential for vascularized tissue engineering. † Presenting Undergrad Author; ‡ Contributing Undergrad Author; * Undergrad Acknowledgment Keywords: Angiogenesis; Matrix Degradability; NorHA; Composite Hydrogels; Vascularized Tissue Engineering

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Purdue University / 2025

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Twisha Tirumani Shivashankar

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