使用双嘧达莫涂层的三维打印生物陶瓷支架在生长颅骨中进行骨组织工程：构建优化及对颅缝开放的影响。
Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency.
机构信息
From the Hansjörg Wyss Department of Plastic Surgery, New York University Langone Health; New York University School of Medicine; the Icahn School of Medicine at Mount Sinai; the Department of Biomaterials, New York University College of Dentistry; and the Division of Translational Medicine, New York University School of Medicine.
出版信息
Plast Reconstr Surg. 2020 Feb;145(2):337e-347e. doi: 10.1097/PRS.0000000000006483.
BACKGROUND
Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated.
METHODS
Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning.
RESULTS
Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations.
CONCLUSION
The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
背景
由β-磷酸三钙组成的三维打印生物陶瓷支架，递送成骨剂双嘧达莫，可治疗骨骼成熟的转化模型中的临界尺寸颅骨缺损。然而，这种结构尚未应用于生长中的颅面模型。在这项研究中，作者将三维打印的生物陶瓷/双嘧达莫支架植入生长中的颅骨动物模型中，并评估了几何支架设计和双嘧达莫浓度对骨生长的影响。还评估了对生长中的缝的潜在不利影响。
方法
在 5 周龄（约 1.1 公斤）新西兰白兔（16 只分析）中创建双侧颅骨缺损（10 毫米）。三维打印的生物陶瓷支架以四象限形式构建，由不同的孔径（220、330 和 500 μm）组成。每个支架均用胶原蛋白包被，并浸泡在不同浓度的双嘧达莫（100、1000 和 10000 μM）中。对照为空缺陷。术后 8 周处死动物。使用微计算机断层扫描、三维重建和非脱钙组织学切片分析颅骨。
结果
支架诱导的骨生长明显大于空缺陷中的骨生长（p = 0.02）。大支架孔，500 μm，涂有 1000 μM 双嘧达莫，产生了最多的骨生长和最低程度的支架存在于缺陷中。组织学显示血管化编织和板层骨，以及支架格子内血管管的初始形成。微计算机断层扫描和组织学分析显示颅骨缝通畅，所有双嘧达莫浓度均未见异位骨形成。
结论
作者提出了一种有效的儿科骨组织工程支架设计和双嘧达莫浓度，可有效增强颅骨骨生成，同时保持颅骨缝的通畅。
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