Influence of Mussel-Derived Bioactive BMP-2-Decorated PLA on MSC Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo
Influence of Mussel-Derived Bioactive BMP-2-Decorated PLA on MSC Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo
复制标题
贻贝生物活性 BMP-2 修饰的 PLA 对 MSC 体外行为的影响及体内异位点成骨性的验证
DOI：
10.1021/acsami.8b01547
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发表时间：
2018-04-11
影响因子：
9.5
通讯作者：
Shang, Lijun
中科院分区：
文献类型：
--
作者：
Chen, Zhuoyue;Zhang, Zhen;Shang, Lijun
骨诱导活性在骨愈合和再生中的应用仍是一个具有挑战性的研究课题。重组人骨形态发生蛋白-2 （BMP-2）的治疗应用是一种很有前景的促进成骨的方法。然而，高剂量和不受控制的BMP-2爆发释放可引起水肿、骨过度生长、囊肿样骨形成和炎症。本研究采用1 μ g的低剂量BMP-2设计PLA-PD- bmp，通过贻贝激发的聚多巴胺（PD）辅助实现聚乳酸（PLA）植入物的功能化。首次通过抗原抗体反应直接验证并分析了PD涂层与BMP-2的结合性能和效率，获得的低剂量BMP-2固定的PLA-PD-BMP表面可以使植入物具有引入强干细胞粘附的能力，增强了成骨性。此外，通过大鼠异位骨模型证实了PLA-PD-BMP-2支架的体内成骨作用，这被标记为成骨活性证据的“金标准”。显微计算机断层扫描、杨氏模量和组织学分析也证明了移植1 μ g BMP-2的PLA-PD-BMP可以诱导骨形成。因此，本研究的方法可以作为一个模型系统，将其他生长因子固定在各种不同类型的聚合物基质上。高度仿生学的贻贝衍生策略可以！因此，以一种简便、安全、有效的方式提高聚合物基医用植入物的临床效果。
Osteoinductive activity of the implant in bone healing and regeneration is still a challenging research topic. Therapeutic application of recombinant human bone morphogenetic protein-2 (BMP-2) is a promising approach to enhance osteogenesis. However, high dose and uncontrolled burst release of BMP-2 may introduce edema,bone overgrowth, cystlike bone formation, and inflammation. In this study, low-dose BMP-2 of 1 mu g was used to design PLA-PD-BMP for functionalization of polylactic acid (PLA) implants via mussel inspired polydopamine (PD) assist. For the first time, the binding property and efficiency of the PD coating with BMP-2 were directly demonstrated and analyzed using an antigen antibody reaction The obtained PLA-PD-BMP surface immobilized with this low BMP-2 dose can endow the implants with abilities of introducing strong stem cell adhesion add enhanced osteogenicity. Furthermore, in vivo osteoinduction of the PLA-PD-BMP-2 scaffolds was confirmed by a rat ectopic bone model, which is marked as the "gold standard" for the evidence of osteoinductive activity. The microcomputed tomography, Young's modulus, and histology analyses were also employed to demonstrate that PLA-PD-BMP grafted with 1 mu g of BMP-2 can induce bone formation. Therefore, the method in this study can be used as a model system to immobilize other growth factors onto various different types of polymer substrates. The highly biomimetic mussel-derived strategy can! therefore improve the clinical outcome of polymer-based medical implants in a facile, safe, and effective way.