The University of Queensland, School of Dentistry, Herston, Queensland, Australia.
Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Biomaterials. 2021 Feb;269:120671. doi: 10.1016/j.biomaterials.2021.120671. Epub 2021 Jan 8.
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 PCL-BMP-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.
在口腔颌面外科学领域，如何在现有骨组织之外实现三维稳定的骨再生是一个重大挑战。本研究中，我们证明了一种使用增材制造技术制造的高多孔可吸收支架可实现可重复的骨外形成，并防止骨吸收。我们评估了一种使用增材制造技术制造的具有医学级聚己内酯（mPCL）双相支架的能力，该支架模仿颌骨结构，由 3D 打印的外壳覆盖内层高度多孔的熔融静电纺丝支架组成，以评估其在骨外绵羊颅盖模型中支持三维稳定骨再生的能力。为了研究骨形成能力（第 1 阶段），将 7 种不同的构建体置于保护罩下，在植入后 8 周进行评估：空对照、具有水凝胶的双相支架（PCL-Gel）、具有 75 或 150μg BMP-2 的 PCL-Gel（PCL-BMP-75 和 PCL-BMP-150）、仅水凝胶（Gel）、含有 75 或 150μg BMP-2 的水凝胶（Gel-BMP-75 和 Gel-BMP-150）。为了评估尺寸稳定性（第 2 阶段），在另一组中，以类似的方式将每组 Gel-BMP-150 和 PCL-BMP-150 的 2 个样本植入 5 只动物中，在 8 周的愈合后，去除保护罩，并将钛植入物放置在再生骨中，再愈合 8 周。使用微计算机断层扫描、组织学和组织形态计量学评估骨形成和骨整合。在第 1 阶段，发现含有 BMP-2 的组的骨形成增强，特别是 PCL-BMP 构建体，以可重复的方式实现了全骨高度的再生。较高剂量的 BMP-2 并未显著增加骨体积。在尺寸稳定性评估（第 2 阶段）中，去除保护罩后，双相支架可防止骨吸收，而在没有支架的情况下，先前在水凝胶中形成的骨经历了广泛的吸收。这归因于双相支架的空间维持特性和尺寸稳定性。钛植入物与双相支架内新形成的骨整合。总之，用 BMP-2 功能化的增材制造双相支架促进了支持牙种植体骨整合的三维稳定骨再生。
