Department of Orthopaedic Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China; Translational Research Centre of Regenerative Medicine and 3D Printing Technologies, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China.
Department of Orthopaedic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.
Biomaterials. 2018 Aug;175:44-60. doi: 10.1016/j.biomaterials.2018.05.017. Epub 2018 May 15.
Great effort has been spent to promote the vascularization of tissue engineering bone grafts (TEBG) for improved therapeutic outcome. However, the thorough vascularization especially in the central region still remained as a major challenge for the clinical translation of TEBG. Here, we developed a new strategy to construct a centrally vascularized TEBG (CV-TEBG) with unique core-shell composite structure, which is consisted of an angiogenic core and an osteogenic shell. The in vivo evaluation in rabbit critical sized femoral defect was conducted to meticulously compare CV-TEBG to other TEBG designs (TEBG with osteogenic shell alone, or angiogenic core alone or angiogenic core+shell). Microfil-enhanced micro-CT analysis has been shown that CV-TEBG could outperform TEBG with pure osteogenic or angiogenic component for neo-vascularization. CV-TEBG achieved a much higher and more homogenous vascularization throughout the whole scaffold (1.52-38.91 folds, p < 0.01), and generated a unique burrito-like vascular network structure to perfuse both the central and peripheral regions of TEBG, indicating a potential synergistic effect between the osteogenic shell and angiogenic core in CV-TEBG to enhance neo-vascularization. Moreover, CV-TEBG has generated more new bone tissue than other groups (1.99-83.50 folds, p < 0.01), achieved successful bridging defect with the formation of both cortical bone like tissue externally and cancellous bone like tissue internally, and restored approximately 80% of the stiffness of the defected femur (benchmarked to the intact femur). It has been further observed that different bone regeneration patterns occurred in different TEBG implants and closely related to their vascularization patterns, revealing the potential profound influence of vascularization patterns on the osteogenesis pattern during defect healing.
人们付出了巨大努力来促进组织工程骨移植物（TEBG）的血管化，以提高治疗效果。然而，彻底的血管化，特别是在中央区域，仍然是 TEBG 临床转化的主要挑战。在这里，我们开发了一种新策略来构建具有独特核心-壳复合结构的中央血管化 TEBG（CV-TEBG），其由血管生成核心和成骨壳组成。在兔临界尺寸股骨缺损的体内评估中，我们精心比较了 CV-TEBG 与其他 TEBG 设计（仅具有成骨壳的 TEBG、仅具有血管生成核心的 TEBG 或血管生成核心+壳）。微柱增强微 CT 分析表明，CV-TEBG 在新血管生成方面优于具有纯成骨或血管生成成分的 TEBG。CV-TEBG 在整个支架中实现了更高和更均匀的血管化（1.52-38.91 倍，p<0.01），并产生了独特的玉米饼状血管网络结构，以灌注 TEBG 的中央和外周区域，表明 CV-TEBG 中成骨壳和血管生成核心之间存在潜在的协同作用，以增强新血管生成。此外，CV-TEBG 比其他组产生了更多的新骨组织（1.99-83.50 倍，p<0.01），成功地桥接了缺损，形成了外部皮质骨样组织和内部松质骨样组织，并恢复了缺损股骨约 80%的刚度（与完整股骨基准）。进一步观察到不同的骨再生模式发生在不同的 TEBG 植入物中，并且与它们的血管化模式密切相关，这揭示了血管化模式对缺损愈合过程中成骨模式的潜在深远影响。
