Huang Peng, Bi Xiaoping, Gao Jin, Sun Lijie, Wang Shaofei, Chen Shuo, Fan Xianqun, You Zhengwei, Wang Yadong
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, 2999 North Renmin Road, Shanghai 201620, P. R. China.
J Mater Chem B. 2016 Mar 28;4(12):2090-2101. doi: 10.1039/c5tb02542g. Epub 2016 Mar 8.
Phosphorylated polymers are promising for bone regeneration because they may recapitulate the essence of the phosphorylated bone extracellular matrix (ECM) to build an instructive environment for bone formation. However, most of the existing synthetic phosphorylated polymers are not fully biodegradable; thus, they are not ideal for tissue engineering. Here, we designed and synthesized a new phosphorylated polymer, poly(sebacoyl diglyceride) phosphate (PSeD-P), based on the biodegradable osteoconductive backbone PSeD. To our knowledge, PSeD-P is the first polymer to integrate the osteoinductive moiety β-glycerol phosphate (β-GP). PSeD-P shows good biodegradability and can be readily fabricated on 3D porous scaffolds. It has a porous structure with interconnected macropores (75-150 μm) and extensive micropores (several microns). PSeD-P promotes the adhesion, proliferation, and maturation of osteoblasts more effectively than poly(lactic-co-glycolic acid) (PLGA). Furthermore, PSeD-P induces a significantly higher expression of osteogenic biomarkers and ALP activity in mesenchymal stem cells (MSCs) compared to its non-phosphorylated precursor, PSeD. The level of improvement is comparable to free β-GP in culture medium. More importantly, without using β-GP, the typical mineralization promoter in osteogenic culture media, PSeD-P substantially induces the mineralization of the ECM in MSCs, which is totally absent using PSeD under identical culture conditions. PSeD-P provides a new strategy to integrate bioactive phosphates viaβ-GP into biomaterial, and has promise for bone regeneration applications. In addition, the synthetic method is versatile; both the backbone and the side phosphate groups could be readily tailored to generate a family of phosphorylated polymers for a wide range of biomedical applications.
磷酸化聚合物在骨再生方面具有潜力，因为它们可能重现磷酸化骨细胞外基质（ECM）的本质，为骨形成构建一个具有指导作用的环境。然而，现有的大多数合成磷酸化聚合物并非完全可生物降解；因此，它们并非组织工程的理想选择。在此，我们基于可生物降解的骨传导主链聚癸二酸二甘油酯（PSeD）设计并合成了一种新型磷酸化聚合物——聚（癸二酰二甘油）磷酸酯（PSeD-P）。据我们所知，PSeD-P是第一种整合了骨诱导部分β-甘油磷酸酯（β-GP）的聚合物。PSeD-P具有良好的生物降解性，并且能够很容易地制备在三维多孔支架上。它具有相互连通的大孔（75 - 150μm）和广泛的微孔（几微米）的多孔结构。与聚乳酸-乙醇酸共聚物（PLGA）相比，PSeD-P能更有效地促进成骨细胞的黏附、增殖和成熟。此外，与未磷酸化的前体PSeD相比，PSeD-P在间充质干细胞（MSCs）中诱导成骨生物标志物的表达和碱性磷酸酶（ALP）活性显著更高。改善程度与培养基中的游离β-GP相当。更重要的是，在不使用成骨培养基中典型的矿化促进剂β-GP的情况下，PSeD-P能显著诱导MSCs中细胞外基质的矿化，而在相同培养条件下使用PSeD时则完全没有矿化现象。PSeD-P提供了一种通过β-GP将生物活性磷酸盐整合到生物材料中的新策略，在骨再生应用方面具有前景。此外，合成方法具有通用性；主链和侧链磷酸基团都可以很容易地进行调整，以生成一系列用于广泛生物医学应用的磷酸化聚合物。
