Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings
Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings
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DOI：
10.1093/rb/rbu019
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发表时间：
2015-03-01
影响因子：
6.7
通讯作者：
Hollinger, Jeffrey O.
中科院分区：
文献类型：
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作者：
Kim, Jinku;Magno, Maria Hanshella R.;Hollinger, Jeffrey O.
下一代合成骨移植疗法很可能由可吸收聚合物与生物活性成分组合而成。在本文中，我们继续探索 E1001(1k)（一种酪氨酸衍生的聚碳酸酯）作为骨科植入材料。具体来说，我们使用可降解、无毒且具有骨传导性的 E1001(1k) 来制造多孔骨再生支架，并通过两种不同类型的磷酸钙 (CP) 涂层增强：在一种情况下，纯二水合磷酸二钙沉淀在支架表面及其整个多孔结构 (E1001(1k) + CP）。在另一种情况下，骨基质矿物质（BMM）如锌、锰和氟化物在二水磷酸二钙涂层（E1001（1k）+ BMM）内共沉淀。将这些支架组合物相互比较，并与 ChronOS（Synthes USA，West Chester，PA，USA）进行比较，ChronOS 是一种临床使用的骨移植替代品（BGS），在我们的实验设计中充当阳性对照。该 BGS 由聚（丙交酯 co-e-己内酯）和 β-磷酸三钙组成。我们使用已建立的兔颅盖临界尺寸缺损模型来确定三种支架组合物中每一种的缺损内的骨再生。 2、4、6、8和12周后通过微计算机断层扫描（mCT）和组织学测定新骨形成。实验性酪氨酸衍生的聚碳酸酯，用二水合磷酸二钙 E1001(1k) + CP 增强，支持缺损内显着的骨形成，并且优于含有 BMM、E1001(1k) + BMM 混合物的相同支架。与市售 BGS 的比较因 E1001(1k) 支架实验室制剂观察到的骨形成差异较大而变得复杂。在所有时间点上，E1001(1k) + CP 都有优于商业 BGS 的趋势。然而，只有在 6 周的时间点，这种趋势才达到统计显着性。 mCT 数据的详细分析表明，使用 E1001(1k) + CP 处理的种植部位的骨形成从 2 周到 12 周有所增加。植入后 2 周和 4 周，E1001(1k) + CP 支架与植入部位骨边界接触的界面处发生骨形成。此后，在第 6、8 和 12 周期间，整个 E1001(1k) + CP 测试种植体的骨形成不断进展。 E1001(1k) + BMM 支架或临床使用的 BGS 没有观察到这种趋势。我们的结果表明 E1001(1k) + CP 应进一步测试骨再生应用。
Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components. In this article, we continue our exploration of E1001(1k), a tyrosine-derived polycarbonate, as an orthopedic implant material. Specifically, we use E1001(1k), which is degradable, nontoxic, and osteoconductive, to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate (CP) coatings: in one case, pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure (E1001(1k) + CP). In the other case, bone matrix minerals (BMM) such as zinc, manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating (E1001(1k) + BMM). These scaffold compositions were compared against each other and against ChronOS (Synthes USA, West Chester, PA, USA), a clinically used bone graft substitute (BGS), which served as the positive control in our experimental design. This BGS is composed of poly(lactide co-e-caprolactone) and beta-tricalcium phosphate. We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions. New bone formation was determined after 2, 4, 6, 8 and 12 weeks by micro-computerized tomography (mCT) and histology. The experimental tyrosine-derived polycarbonate, enhanced with dicalcium phosphate dihydrate, E1001(1k) + CP, supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM, E1001(1k) + BMM. The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k) scaffolds. At all time points, there was a trend for E1001(1k) + CP to be superior to the commercial BGS. However, only at the 6-week time point did this trend reach statistical significance. Detailed analysis of the mCT data suggested an increase in bone formation from 2 through 12 weeks in implant sites treated with E1001(1k) + CP. At 2 and 4 weeks post-implantation, bone formation occurred at the interface where the E1001(1k) + CP scaffold was in contact with the bone borders of the implant site. Thereafter, during weeks 6, 8 and 12 bone formation progressed throughout the E1001(1k) + CP test implants. This trend was not observed with E1001(1k) + BMM scaffolds or the clinically used BGS. Our results suggest that E1001(1k) + CP should be tested further for osteoregenerative applications.