Novel Surface Coatings Using Oxidized Glycosaminoglycans as Delivery Systems of Bone Morphogenetic Protein 2 (BMP-2) for Bone Regeneration
Novel Surface Coatings Using Oxidized Glycosaminoglycans as Delivery Systems of Bone Morphogenetic Protein 2 (BMP-2) for Bone Regeneration
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DOI：
10.1002/mabi.201800283
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发表时间：
2018-11-01
影响因子：
4.6
通讯作者：
Groth, Thomas
中科院分区：
文献类型：
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作者：
Anouz, Reema;Repanas, Alexandros;Groth, Thomas
骨的组织工程需要以局部、持续的方式输送生长因子。其中，壳聚糖作为聚阳离子，肝素和硫酸软骨素作为天然或氧化的聚阴离子，通过逐层技术形成多层膜。使用氧化的肝素和氧化的硫酸软骨素可以通过在多阳离子的氨基和氧化的糖胺多聚糖(OGAGs)的醛之间形成亚胺键来实现额外的稳定性。由于这些多层膜是高度亲水性的，C2C12成肌细胞的粘附性可以通过使用特定的4+9 pH区与天然糖胺聚糖或在oGAGs的情况下使用末端的I型胶原层来改善。对种植在骨形态发生蛋白(BMP-2)负载或非负载多层膜上的C2C12成肌细胞的黏附和增殖研究表明，基于OGAG的多层膜中的内在交联性支持细胞黏附、扩散、增殖和随后的细胞分化为成骨细胞。这与用椭偏仪和原子力显微镜研究的oGAGs多层膜的厚度和粗糙度比本地对应的膜厚和粗糙度有关。总而言之，oGAG多层系统提供了稳定的表面涂层，并可作为生物相容性储存库用于BMP-2的持续释放，为涂层植入物和骨修复和再生支架铺平了道路。
Tissue engineering of bone requires the delivery of growth factors in a localized, sustained manner. Here, chitosan is used as polycation, while heparin and chondroitin sulfate are employed either as native or oxidized polyanions for formation of multilayers by layer-by-layer technique. The use of oxidized heparin and oxidized chondroitin sulfate permits additional stabilization by cross-linking through imine bond formation between amino groups of polycations and aldehydes of oxidized glycosaminoglycans (oGAGs). Since these multilayers are highly hydrophilic, adhesion of C2C12 myoblasts is improved either by the use of a specific 4 + 9 pH regime with native glycosaminoglycans or a terminal collagen I layer in case of oGAGs. Adhesion and proliferation studies with C2C12 myoblasts, seeded either on bone morphogenetic protein (BMP-2) loaded or non-loaded multilayers, show that intrinsic cross-linking in oGAG-based multilayers supports cell adhesion, spreading, proliferation, and subsequent cell differentiation into osteoblasts. This is related to higher thickness and roughness of multilayers made of oGAGs compared to their native counterparts studied by ellipsometry and atomic force microscopy. Taken together, oGAG multilayer systems provide stable surface coatings and are useful as biocompatible reservoirs for sustained release of BMP-2, paving the way for coating implants and scaffolds for repair and regeneration of bone.