Development and Characterization of Modular Biomaterial Platforms for Cartilage Tissue Engineering Applications

dc.contributor.advisorMikos, Antonios G
dc.creatorPearce, Hannah Abigail
dc.date.accessioned2022-09-23T16:08:30Z
dc.date.available2022-09-23T16:08:30Z
dc.date.created2022-08
dc.date.issued2022-06-17
dc.date.submittedAugust 2022
dc.date.updated2022-09-23T16:08:30Z
dc.description.abstractBiomaterials are a powerful tool in tissue engineering. Biomaterials impart cues to the body, can be encapsulated with cells, promote cellular infiltration, and direct differentiation. Beneath these functions of biomaterials are the physicochemical properties that drive much of these phenomena. This thesis outlines the systematic characterization and demonstration of how material physicochemical properties dictate biomaterial behavior and ultimately determine the success of achieving tissue remodeling in a cartilage explant model. Firstly, a thiolated gelatin microparticle (GMP) platform was developed and characterized. For this work it was hypothesized that by thiolating gelatin before microparticle formation, a versatile platform would be created that preserves the cytocompatibility of gelatin, while enabling post-fabrication modification. The thiolated GMPs were demonstrated to be a biocompatible platform for mesenchymal stem cell attachment. Additionally, the thiolated particles were able to be covalently modified with a peptide, demonstrating their promise as a platform for drug delivery applications. Focusing next on an injectable carrier, a poly(N-isopropylacrylamide) (p(NiPAAm)) based hydrogel was developed to determine how covalent peptide conjugation influences hydrogel behavior in vitro. Using a modular poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) crosslinker, peptides were synthesized and covalently clicked to PdBT via azide/alkyne click chemistry. The peptides did not significantly impact the mass sol fraction while significantly increasing the equilibrium swelling of the hydrogels. This hydrophilicity of the network was demonstrated to be the most important factor in dictating hydrogel behavior over time in vitro. Focusing next on how these complex physiochemical properties can influence cell behavior in a biologically relevant ex vivo system, a study was designed in which the charge and thermogelation behavior of p(NiPAAm)-based hydrogels was investigated. A positively, neutrally, or negatively charged peptide was conjugated to the PdBT crosslinker and cellular infiltration and tissue integration were assessed in the explant. Negatively charged hydrogels whose thermogelation behavior changed over time were demonstrated to promote the greatest tissue integration when compared to the positive and neutral gels of the same thermogelling polymer formulation. This thesis demonstrates the important role that material physicochemical properties play in dictating cell and tissue behavior and can inform future tissue engineering strategies.
dc.format.mimetypeapplication/pdf
dc.identifier.citationPearce, Hannah Abigail. "Development and Characterization of Modular Biomaterial Platforms for Cartilage Tissue Engineering Applications." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113233">https://hdl.handle.net/1911/113233</a>.
dc.identifier.urihttps://hdl.handle.net/1911/113233
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectGelatin microparticles
dc.subjecthydrogels
dc.subjectthermogels
dc.subjectclick chemistry
dc.subjectpeptides
dc.subjectcartilage
dc.subjecttissue engineering
dc.titleDevelopment and Characterization of Modular Biomaterial Platforms for Cartilage Tissue Engineering Applications
dc.typeThesis
dc.type.materialText
thesis.degree.departmentBioengineering
thesis.degree.disciplineEngineering
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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