Department of Biomaterials, New York University College of Dentistry, New York, New York, 10010.
College of Medicine, SUNY Upstate Medical University, Syracuse, New York, New York, 13210.
J Orthop Res. 2019 Dec;37(12):2499-2507. doi: 10.1002/jor.24424. Epub 2019 Aug 8.
There are over two million long bone defects treated in the United States annually, of which 5% will not heal without significant surgical intervention. While autogenous grafting is the standard of care in simple defects, a customized scaffold for large defects in unlimited quantities is not available. Recently, a three-dimensionally (3D)-printed bioactive ceramic (3DPBC) scaffold has been successfully utilized in the of repair critical-sized (CSD) long bone defects in vivo. In this study, 3DPBC scaffolds were augmented with dipyridamole (DIPY), an adenosine A2A receptor (A R) indirect agonist, because of its known effect to enhance bone formation. CSD full thickness segmental defects (11 mm × full thickness) defects were created in the radial diaphysis in New Zealand white rabbits (n = 24). A customized 3DPBC scaffold composed of β-tricalcium phosphate was placed into the defect site. Groups included scaffolds that were collagen-coated (COLL), or immersed in 10, 100, or 1,000 μM DIPY solution. Animals were euthanized 8 weeks post-operatively and the radii/ulna-scaffold complex retrieved en bloc, for micro-CT, histological, and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). MicroCT reconstructions illustrated bone in-growth throughout the scaffold, with an increase in bone volume dependent on the DIPY dosage. The histological evaluation did not indicate any adverse immune response while revealing progressive remodeling of bone. These customized biologic 3DPBC scaffolds have the potential of repairing and regenerating bone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2499-2507, 2019.
美国每年有超过两百万例长骨缺损需要治疗，其中约 5%的患者如果不进行重大手术干预，将无法愈合。虽然自体移植物是治疗简单缺陷的标准方法，但无法获得大量用于治疗大缺陷的定制支架。最近，一种三维（3D）打印的生物活性陶瓷（3DPBC）支架已成功用于体内修复临界尺寸（CSD）长骨缺损。在这项研究中，3DPBC 支架中加入了双嘧达莫（DIPY），一种腺苷 A2A 受体（A R）间接激动剂，因为它具有增强骨形成的已知作用。在新西兰白兔的桡骨干（n = 24）中创建了全厚度节段性缺损（~11mm×全厚度）的 CSD 全厚度节段性缺损。将由β-磷酸三钙组成的定制 3DPBC 支架放置在缺陷部位。实验组包括涂有胶原蛋白（COLL）的支架，或浸入 10、100 或 1000μM DIPY 溶液中的支架。动物在术后 8 周时安乐死，并整块取出桡骨/尺骨-支架复合物，进行 micro-CT、组织学和力学分析。仅在支架孔内评估骨生长，并通过 microCT 和先进的重建软件进行评估。利用纳米压痕法评估新再生骨的弹性模量（E）和硬度（H）来评估生物力学性能。microCT 重建图显示了整个支架内的骨向内生长，骨体积的增加取决于 DIPY 的剂量。组织学评估未表明存在任何不良免疫反应，同时揭示了骨的进行性重塑。这些定制的生物 3DPBC 支架具有修复和再生骨的潜力。©2019 骨科研究协会。由 Wiley Periodicals, Inc. 出版。J Orthop Res 37:2499-2507, 2019.
