Browsing by Author "Farsheed, Adam Cyrus"

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    Fabrication of Macroscopic Nanofibrous Multidomain Peptide Hydrogels to Engineer Biological Tissues
    (2024-04-12) Farsheed, Adam Cyrus; Grande-Allen, K. Jane; Hartgerink, Jeffrey
    Fibrous extracellular matrix (ECM) proteins mechanically support cells and are hierarchically organized within macroscopic biological tissues. A longstanding goal of tissue engineering has been to fabricate scaffolds that mimic this organization, but it has been difficult to simultaneously mirror both micro and macroscale tissue complexity. Biomaterial design innovations have fostered the creation of synthetic ECM-mimetic hydrogels that recapitulate the mechanical and chemical properties of soft tissues. Still, the creation of large scaffolds at high fidelity has remained a bottleneck and is especially challenging when using soft biomaterials. Three- dimensional (3D) printing has emerged as a fabrication technology able to meet this goal due to its layer-by-layer working principal, but the number of hydrogels that have been adopted for 3D printing has remained limited. For over a decade, the Hartgerink lab has developed a synthetic class of biomaterials called multidomain peptides (MDPs), which form nanofibrous hydrogels that are useful for a variety of biomedical applications. My thesis presents the optimization of MDPs for 3D printing and the development of methods to create macroscopic MDP hydrogels with hierarchical order. In addition, I explore how biomaterial charge and fibrous alignment cues can be used to direct cellular spreading and engineer tissues from the bottom up. In the first chapter, I contextualize my work by reviewing the extracellular matrix, hydrogels, 3D printing of hydrogels, and MDPs. In the second chapter, I optimize MDPs for extrusion 3D printing and fabricate complex hydrogel structures and multi-material prints. In addition, I show how MDP charge can be used to control cell growth, which allows chemical functionality to provide an additional dimension to printing complexity. In the third chapter, I develop an extrusion-based fabrication strategy using MDPs to generate nanofibrous hydrogels that possess a spectrum of fibrillar alignments. In addition, I show how anisotropic MDP hydrogels can be used to directionally guide cellular growth, while differences in cell-matrix interactions determine a cell’s ability to understand nanofibrous alignment cues. In the fourth chapter, I present progress towards fabricating macroscopic MDP scaffolds with local anisotropy by optimizing support bath assisted 3D printing.