Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, Cleveland, OH, USA.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
J Biomed Mater Res B Appl Biomater. 2018 Feb;106(2):520-532. doi: 10.1002/jbm.b.33857. Epub 2017 Feb 14.
An exploratory pilot study shows that a rodent mandibular defect model is useful in determining the biological response to a nanophase collagen/apatite composite designed as a biomimetic load-bearing bone substitute. Using a critical size defect, eight groups of rats (n = 3) were implanted with four renditions of the nanophase bone substitute (NBS) biomaterial. Each rendition was tested with and without recombinant human bone morphogenetic protein 2 (BMP2). NBS biomaterial renditions were: baseline, hyper-densified, d-ribose crosslinked, and d-ribose crosslinked and hyper-densified. Biological outcomes were assessed surgically, radiologically, and histologically. With the limited power available due to the small N's involved, some interesting hypotheses were generated that will be more fully investigated in future studies. BMP2 loaded NBS, when uncrosslinked, resulted in robust bone formation in the entire defect volume (regardless of porosity). Unloaded NBS were well tolerated but did not cause significant new bone formation in the defect volume. Densification alone had little effect on in vivo performance. Crosslinking thwarted implant uptake of BMP2 and resulted in fibrous encapsulation. It is concluded that the nanophase bone substitute is well tolerated in this bone defect model. When loaded with BMP2, implantation resulted in complete bony healing and defect closure with implant density (porosity) having little effect on bone healing or remodeling. Without BMP2 the biomaterial did not result in defect closure. Crosslinking, necessary to increase mechanical properties in an aqueous environment, disrupts osteointegration and BMP2 uptake. Alternate implant fabrication strategies will be necessary to achieve an improved balance between material strength and osteointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 520-532, 2018.
一项探索性初步研究表明，啮齿动物下颌骨缺损模型可用于确定对纳米相胶原/磷灰石复合材料的生物学反应，该复合材料设计为仿生承重骨替代物。使用临界尺寸缺损，将八组大鼠（n = 3）植入四种纳米相骨替代物（NBS）生物材料。每种材料都进行了不含和含重组人骨形态发生蛋白 2（BMP2）的测试。NBS 生物材料版本为：基线、超致密、d-核糖交联、d-核糖交联和超致密。通过手术、放射学和组织学评估生物结果。由于涉及的 N 较小，因此可用的功率有限，产生了一些有趣的假设，这些假设将在未来的研究中得到更充分的研究。负载 BMP2 的 NBS 在未交联时，导致整个缺陷体积（无论孔隙率如何）都有大量骨形成。未负载的 NBS 耐受良好，但在缺陷体积中未引起明显的新骨形成。单独致密化对体内性能几乎没有影响。交联阻止了 BMP2 对植入物的吸收，并导致纤维包裹。结论是，纳米相骨替代物在这种骨缺损模型中耐受良好。当负载 BMP2 时，植入物导致完全骨性愈合和缺陷闭合，植入物密度（孔隙率）对骨愈合或重塑几乎没有影响。没有 BMP2，生物材料不会导致缺陷闭合。交联对于在水介质中提高机械性能是必要的，但会破坏骨整合和 BMP2 吸收。需要替代植入物制造策略，以在材料强度和骨整合之间实现更好的平衡。 © 2017 Wiley Periodicals, Inc. J 生物医学材料研究部分 B：应用生物材料，106B：520-532，2018。
