The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2
The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2
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DOI：
10.1016/j.biomaterials.2008.12.055
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发表时间：
2009-05-01
期刊：
影响因子：
14
通讯作者：
Cool, S. M.
中科院分区：
文献类型：
--
作者：
Sawyer, A. A.;Song, S. J.;Cool, S. M.
骨形态发生蛋白（BMP）在骨修复中的临床应用已被广泛研究，众所周知，合适的载体基质来输送它们对于特定缺损部位内的最佳骨再生至关重要。熔融沉积建模 (FDM) 可以制造具有高重复性和定制设计尺寸的医用级聚ε-己内酯/磷酸三钙 (mPCL-TCP) 支架。在这里，我们将 FDM 制造的 mPCL-TCP/胶原支架与 5 Pig 重组人 (rh)BMP-2 装载，并评估大鼠颅骨临界尺寸缺损内的骨愈合。本研究采用综合方法，利用微型计算机断层扫描 (mu CT)、组织学/组织形态计量学和机械评估来评估新再生的骨骼。到 15 周时，mPCL-TCP/胶原/rhBMP-2 缺陷显示颅骨完全愈合，而非 BMP-2 负载支架显示骨向内生长显着减少，如 mu CT 所证实。组织形态计量学显示，与未处理的支架相比，在第 4 周和第 15 周时，rhBMP-2 组的骨愈合显着增加，尽管 % BV/TV 并未表明整个缺损部位的完全矿化。因此，我们的研究证实，将 microCt 和组织形态计量学相结合对于能够在 3D 中全面研究骨再生非常重要。 rhBMP-2 组的两个时间点的成骨蛋白、1 型胶原蛋白和骨钙蛋白均显着上调。尽管 15 周时各治疗组的矿物质沉积率在统计上是相当的。微压缩和推出强度表明，使用 mPCL-TCP/胶原蛋白/rhBMP-2 治疗的缺损在 15 周时具有优异的骨质量。在所有方式中，进展或愈合都是从空缺损 < mPCL-TCP/胶原 < mPCL-TCP/胶原/rhBMP-2 开始，这提供了证实的数据来支持以下假设：从 FDM 产生的 mPCL-TCP/胶原支架中释放 rhBMP-2 是修复和再生临界尺寸颅面骨缺损的临床相关方法。 Crown 版权所有 (C) 2008 由 Elsevier Ltd 出版。保留所有权利。
Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly epsilon-caprolactone/tricalcium phosphate (mPCL-TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL-TCP/collagen scaffolds with 5 Pig recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing micro-computed tomography (mu CT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL-TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non-BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by mu CT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type 1 collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups. micro-compression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL-TCP/collagen/rhBMP-2. Consistently over all modalities, the progression or healing was from empty defect < mPCL-TCP/collagen < mPCL-TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL-TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved.