Development of polyHIPE scaffolds for improved bone regeneration




Dhavalikar, Prachi Santosh

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Critical size bone defects resulting from trauma or disease are challenging to treat due to the size and shape of the defect. Autologous tissue remains the gold standard due to the superior healing potential but harvesting material is challenging due to donor site complications. We have designed a synthetic scaffold system based on emulsion-templating to create porous scaffolds for bone grafting to address these limitations. These polymerized high internal phase emulsions (polyHIPEs) are biodegradable, maintain strong mechanical properties, and can be applied as injectable bone grafts or 3D printed for improved integration at the defect site. The objective of this work was to increase the regenerative capabilities of polyHIPEs by improving the scaffold structure and biocompatibility to facilitate cell-material interactions. First, a series of novel experimental protocols were developed that advanced fabrication and characterization of polyHIPE grafts. Next, compositional and processing variables of HIPE fabrication were tuned to increase polyHIPE pore size for enabling cell infiltration and vascularization. Studies demonstrated tuning macromer viscosity enabled fabrication of scaffolds with target pore sizes > 100 μm. To supplant the use of organic solvents to control macromer viscosity, a biocompatible, reactive diluent was identified for injectable applications of these materials. Finally, this target composition was used to fabricate emulsions stabilized with hydroxyapatite nanoparticles (nHA) to eliminate use of surfactants and improve scaffold biocompatibility. This strategy enabled in situ surface modification of the pore surface facilitating presentation of bioactive components for directing cell behaviors. nHA-stabilized foams maintained superior mechanical properties, improved biocompatibility, and target pore sizes as compared to the traditional surfactant-stabilized foams. In summary, tuning compositional and fabrication parameters allowed for optimizing structural and biological properties of polyHIPE scaffolds, improving their potential to serve as bone replacements. In parallel, development of novel fabrication and characterization protocols supported current progress. Together, this body of work establishes the fundamental knowledge for various platforms that can be utilized to achieve critical design requirements for future polyHIPEs in tissue engineering and other applications.


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