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Templated Hybrid Hydrogels for Osteochondral Repair
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A synthetic materials-guided approach, wherein the scaffold’s chemical and physical properties alone instruct cellular behavior for tissue regeneration, has the potential to repair clinically pervasive osteochondral defects (OCDs) without the use of exogenous growth factors. Poly(ethylene glycol) diacrylate (PEG-DA) hydrogels are widely utilized in tissue regeneration, but lacks macroporosity for osteoconduction and are also not strongly bioactive (i.e. inducing mineralization for bone bonding) or osteoinductive (i.e. inducing mesenchymal stem cell [MSC] differentiation toward an osteoblastic-lineage). Previously, work by Grunlan and coworkers established that inclusion of star poly(dimethyl siloxane) methacrylate (PDMSstar-MA) with PEG-DA produced hydrogels with enhanced bioactivity and osteoinductivity. Furthermore, fabrication with solvent-induced phase separation and a salt template (“SIPS/salt”) yielded interconnected, macroporous scaffolds with excellent distribution of the siloxane macromer. Towards achieving osteochondral regeneration, this work sought to prepare macroporous PEG-based hydrogel scaffolds that included siloxane or phosphonated-siloxane macromers, ultimately prepared as monolithic scaffolds with spatial control of chemical and physical properties. In a first study, SIPS/salt scaffolds were prepared with PDMSstar-MA of two number average molecular weights (Mn’s) (2k and 7k) with varying PDMSstar-MA:PEG-DA ratios and template salt sizes. Interconnected macropore size was tuned by the salt size, and a more uniform distribution was achieved with a lower Mn PDMSstar-MA. All PDMSstar-PEG hydrogels were confirmed to be bioactive upon exposure to 1X simulated body fluid (SBF) and, when cultured with human bone marrow derived MSCs (hBMSCs) for 14 days, displayed a PDMSstar-MA dose-dependent increase in osteogenesis. In a second study, to further increase bioactivity and osteoinductivity, a siloxane macromer with pendant phosphonate groups, poly(diethyl(2-(propylthio)ethyl) phosphonate methylsiloxane) diacrylate (PPMS-DA), was synthetized. SIPS/salt PPMS:PEG scaffolds showed an enhanced osteogenic potential versus PDMS:PEG scaffolds when cultured with hBMSCs for 14 and 28 days. Finally, to afford spatial control of chemical and physical properties, a method was developed to prepare monolithic scaffolds from such individual scaffolds, termed ‘hydrogel scaffolds with spatially tunable chemistries and arrangements’ (SSTACs). Demonstrated with several SSTAC designs, the desired spatial distribution of chemistry and pore size was confirmed. Moreover, the interfaces of SSTACs were shown to lack a hard boundary and achieved good mechanical integrity.
Frassica, Michael T. (2020). Templated Hybrid Hydrogels for Osteochondral Repair. Doctoral dissertation, Texas A&M University. Available electronically from