Department of Prosthodontics, College of Dentistry, Yonsei University, Seoul 03722, Republic of Korea.
College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea.
Int J Mol Sci. 2024 Apr 23;25(9):4604. doi: 10.3390/ijms25094604.
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.
大块骨缺损的再连接和修复是临床面临的重大挑战。传统策略主要涉及将骨支架与种子细胞和/或生长因子结合,以调节成骨和血管生成。然而,这些治疗方法存在与免疫原性、致瘤性、生物活性和现货移植相关的固有问题。植入骨移植物所产生的生物微环境在启动骨再生级联反应中起着至关重要的作用。为了解决这个问题,开发了一种由羟基磷灰石(HA)和氧化铝(Al)组成的高多孔双相陶瓷合成骨移植物。该移植物用于修复临界节段性缺损,在犬胫骨中制造了 2 厘米节段性缺损。使用闪烁扫描、微 CT、组织学和动态组织形态计量学评估愈合后合成骨移植物内的骨再生情况。该技术产生的孔径范围为 230-430μm 的初级孔、40-70μm 的二级内微孔和 200-400nm 的三级亚微米表面孔。这三个组件旨在模拟小梁骨网络,并提供体液吸附、扩散、营养供应、细胞周围的交流和细胞锚固。总孔隙率为 82.61±1.28%。微 CT 成像和组织学分析都提供了大量证据,证明了强大的骨形成和临界缺损的成功再连接。此外,组织学显示在新形成的骨区域内存在血管化,在植入后 8 周时清楚地显示出小梁骨和皮质骨形成。