Title:
Proof-of-Concept of a Jagged1-functionalized PEG-4MAL Hydrogel
Proof-of-Concept of a Jagged1-functionalized PEG-4MAL Hydrogel
Author(s)
Ravikumar, Nithin
Advisor(s)
Goudy, Steven L
García, Andrés J.
García, Andrés J.
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Abstract
Craniofacial bone deformities can arise from injuries, congenital defects, cancer, or other causes, leaving patients with impairments and psychological stress. Reconstruction of bone through bone grafts or bone anabolic agents such as bone morphogenetic protein-2 (BMP-2) have been clinically successful but have drawbacks with limited alternative therapies. Growing interest in delivering and presenting the Notch ligand Jagged1 (JAG1) has inspired research into leveraging it for osteoinductive biomaterials. Recent work from our lab as produced a proof-of-concept delivery strategy in which JAG1 is immobilized on dynabeads and delivered in a 4-arm poly(ethylene glycol) maleimide (PEG-4MAL) hydrogel. Despite success in inducing osteogenic differentiation and bone formation, the lack of FDA approval for dynabeads is an obstacle for translation that motivates the search for an alternative immobilization strategy. In this thesis, we explore a potential strategy for immobilizing JAG1 onto a PEG-4MAL hydrogel. We modified JAG1 through PEGylation with a thiol-terminated linear chain PEG that adds free thiols (-SH) capable of conjugating with the maleimide groups of hydrogel backbone. The resulting modified protein, JAG1-PEG-SH, exhibited increased immobilization compared to its unmodified form. Additionally, hydrogels with the PEGylated JAG1 demonstrated osteoinductive properties without diminished bioactivity that suggest that this platform may have future potential as a novel bone-regenerating biomaterial.
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Date Issued
2022-08-01
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Thesis