From the Hansjörg Wyss Department of Plastic Surgery and the Division of Translational Medicine, Department of Medicine, New York University Langone Health; the Department of Biomaterials and Biomimetics, New York University College of Dentistry; and the Icahn School of Medicine at Mount Sinai.
Plast Reconstr Surg. 2019 Aug;144(2):358-370. doi: 10.1097/PRS.0000000000005840.
Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds.
Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 μm of dipyridamole (n = 6), 10,000 μm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test.
Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-μm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-μm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 μm versus 10,000 μm dipyridamole; p = 0.104), and rhBMP-2-coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 μm dipyridamole, and p = 0.938 versus 10,000 μm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone.
Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.
牙槽裂传统上采用二次骨移植治疗，但这种方法会导致发病率和移植物吸收。虽然重组人骨形态发生蛋白-2（rhBMP-2）正在研究用于牙槽裂修复，但仍存在安全性问题。双嘧达莫是一种已知具有成骨潜力的腺苷受体间接激动剂。本研究比较了双嘧达莫与 rhBMP-2 在使用生物陶瓷支架输送到牙槽裂缺损中的效果。
未成年新西兰白兔行单侧 3.5×3.5mm 牙槽切除，位于生长缝附近。5 只作为阴性对照。其余缺损用三维打印的生物陶瓷支架重建，支架表面涂有 1000μm 的双嘧达莫（n=6）、10000μm 的双嘧达莫（n=7）或 0.2mg/ml 的 rhBMP-2（n=5）。8 周时，定量新骨形成。进行非脱钙组织学评估，并对新骨进行力学评估。统计分析采用广义线性混合模型和 Wilcoxon 秩和检验。
阴性对照组未愈合，而所有三维打印生物陶瓷治疗组均形成新骨桥接。1000μm 双嘧达莫支架再生 28.03±7.38%，10000μm 双嘧达莫支架再生 36.18±6.83%（1000μm 与 10000μm 双嘧达莫相比，p=0.104），rhBMP-2 涂层支架再生 37.17±16.69%的骨（p=0.124 与 1000μm 双嘧达莫相比，p=0.938 与 10000μm 双嘧达莫相比）。组织学/电子显微镜检查未见双嘧达莫改变缝生物，而 rhBMP-2 则显示出早期融合迹象。所有组的愈合均高度细胞化和血管化。与天然骨相比，双嘧达莫或 rhBMP-2 之间在力学性能上无统计学差异。
在未成年骨缺损中，双嘧达莫可产生新骨，无 rhBMP-2 相关的骨溶解和早期融合。
