Vaquette, C., Mitchell, J., Fernandez-Medina, Tulio, Kumar, S., and Ivanovski, S. (2021) Resorbable additively manufactured scaffold imparts dimensional stability to extraskeletally regenerated bone. Biomaterials, 269. 120671.

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Abstract

Dimensionally stable vertical bone regeneration outside of the existing bony envelope is a major challenge in the field of orofacial surgery. In this study, we demonstrate that a highly porous, resorbable scaffold fabricated using additive manufacturing techniques enables reproducible extra-skeletal bone formation and prevents bone resorption. An additively manufactured medical grade polycaprolactone (mPCL) biphasic scaffold mimicking the architecture of the jaw bone, consisting of a 3D-printed outer shell overlying an inner highly porous melt electrowritten scaffold, was assessed for its ability to support dimensionally stable bone regeneration in an extraskeletal ovine calvarial model. To investigate bone formation capacity (stage 1), 7 different constructs placed under a protective dome were assessed 8 weeks post-implantation: Empty control, Biphasic scaffold with hydrogel (PCL-Gel), PCL-Gel with 75 or 150 μg of BMP-2 (PCL-BMP-75 and PCL-BMP-150), hydrogel only (Gel), Gel containing 75 or 150 μg of BMP-2 (Gel-BMP-75 and Gel-BMP-150). To assess dimensional stability (stage 2), in a separate cohort, 5 animals were similarly implanted with 2 samples of each of the Gel-BMP-150 and PCLBMP-150 groups, and after 8 weeks of healing, the protective domes were removed and titanium implants were placed in the regenerated bone and allowed to heal for a further 8 weeks. Bone formation and osseointegration were assessed using micro-computed tomography, histology and histomorphometry. In stage 1, enhanced bone formation was found in the BMP-2 containing groups, especially the PCL-BMP constructs whereby regeneration of full bone height was achieved in a reproducible manner. There was no significant bone volume increase with the higher dose of BMP-2. In the dimensional stability assessment (stage 2), after the rtemoval of the protective dome, the biphasic scaffold prevented bone resorption whereas in the absence of the scaffold, the bone previously formed in the hydrogel underwent extensive resorption. This was attributed to the space maintenance properties and dimensional stability of the biphasic scaffold. Titanium implants osseointegrated into the newly formed bone within the biphasic scaffolds. In conclusion, additively manufactured biphasic scaffolds functionalized with BMP-2 facilitated dimensionally stable bone regeneration that supported dental implant osseointegration.

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