Injectable, Click Functionalized Hydrogels for Osteochondral Tissue Engineering
| dc.contributor.advisor | Mikos, Antonios G | |
| dc.creator | Guo, Jason L | |
| dc.date.accessioned | 2020-12-10T17:38:13Z | |
| dc.date.available | 2021-12-01T06:01:11Z | |
| dc.date.created | 2020-12 | |
| dc.date.issued | 2020-12-03 | |
| dc.date.submitted | December 2020 | |
| dc.date.updated | 2020-12-10T17:38:14Z | |
| dc.description.abstract | Articular cartilage injury affects millions around the world and results in hundreds of thousands of procedures being performed in the US alone. Tissue engineering has emerged as a promising strategy for the generation of functional cartilage tissue. Since the repair of articular cartilage and its function depends on the regeneration of multiple tissues within the osteochondral unit – including cartilage and underlying subchondral bone – osteochondral tissue engineering (OTE) is of great interest to scientists and clinicians. The use of injectable hydrogels and three-dimensionally (3D) printed scaffolds represent two approaches in which biomaterial constructs – often encapsulated with cells – are delivered directly to the site of defect, where they will support tissue regeneration. However, these hydrogels and scaffolds, which are often composed of synthetic polymers, are typically bioinert and thus produce a suboptimal biological response from encapsulated and native cells. The conjugation or delivery of tissue-specific biomolecules for cartilage and bone is thus a critical prerequisite for induction of osteochondral tissue regeneration. This doctoral thesis addresses the need for biologically relevant constructs by developing a modular, click functionalized hydrogel system that utilizes tissue-specific biomolecular cues for bone or cartilage regeneration (Figure 1). To achieve this goal, we developed a novel polymeric crosslinker, poly(glycolic acid)–poly(ethylene glycol)–poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) that can click conjugate biomolecules of diverse size and chemical character via mild, aqueous alkyne-azide cycloaddition. PdBT can be functionalized with bone- and cartilage-specific biomolecules and then used as a crosslinker for the thermoresponsive polymer poly(N-isopropylacrylamide-co-glycidyl methacrylate) (P(NIPAAM-co-GMA)), generating rapidly crosslinked, cytocompatible, and highly swollen hydrogels. We characterized the bioactivity of bone- and cartilage-specific hydrogels in vitro, evaluating their capacity to promote the chondrogenesis and osteogenesis of encapsulated mesenchymal stem cells (MSCs). Additionally, we fabricated bilayered hydrogels with bone- and cartilage-specific components for in vivo implantation in a rabbit model. To further explore the utility of our click conjugation scheme, we applied this chemistry to the tissue-specific functionalization of 3D printable polyesters, an emerging area of interest within the field of tissue engineering. Our first objective was to synthesize PdBT and click conjugate it with osteogenic biomolecules – such as osteogenic bone marrow homing peptide 1 (BMHP1) and glycine-histidine-lysine peptide (GHK) – and chondrogenic biomolecules – such as chondroitin sulfate (CS) and N-cadherin peptide (NC). Injectable hydrogels were developed and characterized by mixing biofunctionalized PdBT crosslinkers and P(NIPAAM-co-GMA). Our second objective was to encapsulate MSCs within these hydrogels and characterize the effects of biomolecule identity and concentration on chondrogenesis and osteogenesis in vitro. Our third objective was to implant bilayered hydrogels for the repair of bone and cartilage in a rabbit femoral condyle defect model to study in vivo osteochondral tissue repair. Our last object was to apply this click bioconjugation scheme to a new application in the biological functionalization of 3D printable synthetic polyesters. Ultimately, the bioconjugation toolset developed in this thesis provides a platform for the tissue-specific functionalization of synthetic polymers for tissue engineering applications. | |
| dc.embargo.terms | 2021-12-01 | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.citation | Guo, Jason L. "Injectable, Click Functionalized Hydrogels for Osteochondral Tissue Engineering." (2020) Diss., Rice University. <a href="https://hdl.handle.net/1911/109645">https://hdl.handle.net/1911/109645</a>. | |
| dc.identifier.uri | https://hdl.handle.net/1911/109645 | |
| dc.language.iso | eng | |
| dc.rights | Copyright 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.subject | bioconjugation | |
| dc.subject | osteochondral | |
| dc.subject | tissue engineering | |
| dc.subject | hydrogel | |
| dc.subject | scaffold | |
| dc.subject | printing | |
| dc.title | Injectable, Click Functionalized Hydrogels for Osteochondral Tissue Engineering | |
| dc.type | Thesis | |
| dc.type.material | Text | |
| thesis.degree.department | Bioengineering | |
| thesis.degree.discipline | Engineering | |
| thesis.degree.grantor | Rice University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy |
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