PDF(Pubmed)
Abstract：
The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 μm as primary pores, 40-70 μm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.
摘要：
大段骨缺损的团聚和修复提出了重大的临床挑战。常规策略主要涉及骨支架与接种细胞和/或生长因子的组合以调节骨生成和血管生成。然而,这些疗法面临着与免疫原性相关的固有问题，肿瘤发生，生物活性，和现成的移植。由植入的骨移植物产生的生物微环境在启动骨再生级联中起着至关重要的作用。为了解决这个问题，高度多孔的双相陶瓷合成骨移植物，由羟基磷灰石(HA)和氧化铝(Al)组成，已开发。该移植物用于修复严重的节段性缺陷，涉及在犬胫骨中产生2厘米的节段性缺陷。使用闪烁显像对合成骨移植物愈合后的骨再生进行评估，Micro-CT,组织学,和动态组织形态计量学。该技术产生了230-430μm范围内的孔径作为主要孔，40-70μm作为次要内部微通道，和200-400nm作为第三亚微米表面孔。这三个组件旨在模拟骨小梁网络并提供体液吸附，扩散,营养供应，细胞周围的交流，和细胞锚定。测量的总孔隙率为82.61±1.28%。Micro-CT成像和组织学分析均提供了可靠的骨形成和关键缺损成功团聚的大量证据。此外，组织学显示新形成的骨骼区域内存在血管化，在植入后8周，可以清楚地显示骨小梁和皮质骨的形成。
