Biomedical Applications of Emulsion Templated Scaffolds

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2014-03-28

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Abstract

Each year, millions of patients undergo reconstructive surgery to treat injuries caused by trauma, deformities, or tumor resection. Repair of these defects often requires the use of tissue grafts to promote healing. Current treatment options rely on a limited supply of donor tissue or synthetic materials that lack bioactivity and have a high rate of revision treatments. Tissue engineered grafts provide a temporary matrix that supports tissue regeneration and circumvents complications associated with traditional treatment options. In addition to biodegradable and biocompatible requirements, an injectable scaffold would offer the advantage of space-filling irregular defects without the need for expensive fabrication to shape or custom-build devices. To this end, we have utilized emulsion templating to create injectable polyHIPE scaffolds that are biodegradable, highly porous, polymerize at body temperature, and possess appropriate and tunable mechanical properties for tissue regeneration.

PolyHIPE grafts developed for this purpose exhibited tunable pore sizes (5 ?m to 1 mm) and a wide range of mechanical properties (modulus = 50 kPa-50 MPa). The biodegradable macromers used in these polyHIPEs were designed to polymerize at body temperature and have a low viscosity prior to cure, eliminating the use of toxic solvents common in fabricating biodegradable polyHIPEs. New methodology was developed to permit the rational selection of macromers based on prediction of molecular hydrophobicity and structural analysis of surfactant chemical structure in contrast to the traditional trial-and-error approach. Redox initiation was also studied as a means to decrease polyHIPE cure times from hours to minutes, comparable to current bone cements used currently in the clinic. This new initiation method also improved mechanical properties and had minimal effects on pore structure. The use of a double-barrel syringe also allowed emulsions to be stored for up to 6 months prior to cure with no negative effects on pore structure.

Finally, these polyHIPEs were used to make porous microspheres, via a double-emulsion technique, to improve scaffold bioactivity. These microspheres successfully incorporated rhBMP-2 growth factor, a potent osteoinductive agent used in many bone graft procedures. Current rhBMP-2 delivery methods are expensive and pose safety risks due to the excessive amounts of growth factor used. These microspheres offer a means to gradually deliver site-specific dosages of rhBMP-2 directly in the polyHIPE scaffolds, potentially improving tissue regeneration.

In summary, we have developed a library of injectable porous materials that can be used to improve tissue regeneration. Furthermore, the emulsion structure-property relationships explored here can be used in designing future polyHIPEs for tissue engineering or other applications.

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