Browsing by Author "Kim, Yu Seon"

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    Evaluating the physicochemical effects of conjugating peptides into thermogelling hydrogels for regenerative biomaterials applications
    (Oxford University Press, 2021) Pearce, Hannah A.; Jiang, Emily Y.; Swain, Joseph W.R.; Navara, Adam M.; Guo, Jason L.; Kim, Yu Seon; Woehr, Andrew; Hartgerink, Jeffrey D.; Mikos, Antonios G.
    Thermogelling hydrogels, such as poly(N-isopropylacrylamide) [P(NiPAAm)], provide tunable constructs leveraged in many regenerative biomaterial applications. Recently, our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol), which crosslinks P(NiPAAm-co-glycidyl methacrylate) via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry. This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels. The physicochemical properties of the hydrogels including the lower critical solution temperature, crosslinking times, swelling, degradation, peptide release and cytocompatibility were evaluated. The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components. Comparable sol fractions were found for all groups, indicating that inclusion of peptides does not impact crosslinking. Moreover, the inclusion of a matrix metalloproteinase-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage. The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time. This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels. These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.
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    Injectable Biomimetic Hydrogel Platforms for Cartilage Regeneration
    (2021-03-04) Kim, Yu Seon; Mikos, Antonios G
    Regeneration of articular cartilage has been a clinical challenge as the tissue lacks the ability to regenerate itself due to its low cell density and avascularity. Surgical methods that are currently being implemented for cartilage repair frequently result in the formation of mechanically inferior fibrous cartilage, leaving a large room for improvement in terms of their clinical outcomes. The field of tissue engineering and regenerative medicine has therefore been exploring innovative solutions for delivering cells and bioactive factors that will, in conjunction, guide the regeneration of healthy cartilage. In this thesis, we sought to develop an injectable therapeutic platform that mimics the cartilage microenvironment and could be used as a cell/biomolecule delivery system for cartilage regeneration applications. To this effect, an injectable hydrogel was developed which consisted of a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and chondroitin sulfate (CS)-based network-forming macromers. In this design, the two CS macromers – modified with adipic acid dihydrazide and N-hydroxysuccinimide, respectively – covalently interacted with each other to form a CS network, with which the TGM could further crosslink and form an injectable hydrogel system. The addition of CS, an anionic polysaccharide, greatly increased the degree of swelling of the hydrogel. The molar content of CS affected the rate of degradation, compressive modulus, as well as cytotoxicity of the hydrogel where hydrogels with higher CS content degraded faster, demonstrated higher compressive strength, but were also more cytotoxic. To establish this system into a cell and biomolecule delivery vehicle, we further reinforced the three-component hydrogel system described in the first study with poly(amidoamine), a crosslinker developed specifically for crosslinking TGM. The resulting TGM-CS dual-network hydrogel was used to investigate the effect of poly(L-lysine) (PLL), a novel bioactive factor shown to affect the skeletal development pathway, on the chondrogenesis of cocultures of mesenchymal stem cells (MSCs) and chondrocytes. PLL did not affect the swelling nor degradation properties of the hydrogel and demonstrated good retention within the bulk hydrogel over 28 days in vitro. In addition, PLL with different molecular weights and concentrations did not affect the viability of encapsulated MSCs. Further studies with different coculture ratios of MSCs and chondrocytes revealed that, while PLL seemed to affect the expression of chondrogenic and hypertrophic genes during early stages of the in vitro culture, the long-term chondrogenesis was mostly governed by the fraction of chondrocytes in cocultures. Histological analysis revealed that the study groups with higher fraction of chondrocytes showed denser secretion of cartilage-like matrix. In the last part of the thesis, we developed an ex vivo study using cartilage explants isolated from articular cartilage of pigs to further investigate the effect of the presence of PLL and chondrocytes on the mechanical properties of the hydrogel. By injecting the hydrogel within the defects generated in the center of the cartilage explants, we were able to analyze both the hydrogel surface stiffness and the degree of integration with the surrounding cartilage.