Effect of Biomaterial Electrical Charge on Bone Morphogenetic Protein-2-Induced In Vivo Bone Formation.
Effect of Biomaterial Electrical Charge on Bone Morphogenetic Protein-2-Induced In Vivo Bone Formation.
复制标题
生物材料电荷对骨形态发生蛋白 2 诱导的体内骨形成的影响。
DOI：
10.1089/ten.tea.2018.0140
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发表时间：
2019
影响因子：
--
通讯作者：
Lu,Lichun
中科院分区：
文献类型：
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作者：
Olthof,MauritsGL;Kempen,DiederikHR;Liu,Xifeng;Dadsetan,Mahrokh;Tryfonidou,MariannaA;Yaszemski,MichaelJ;Dhert,WouterJA;Lu,Lichun
生物材料作为蛋白质载体和支架可以提高骨形态发生蛋白-2（BMP-2）临床应用的安全性和有效性。然而，最佳的支架特性是未知的。固定的带电表面的骨诱导和骨传导能力迄今尚未探索。因此，在这项研究中，我们的目的是研究不同的电状态对BMP-2诱导的骨形成的寡聚[（聚乙二醇）富马酸盐]（OPF）水凝胶的影响。分别使用未改性的OPF（中性电荷）、甲基丙烯酸钠交联的OPF（负电荷）或[2-（甲基丙烯酰氧基）乙基]三甲基氯化铵交联的OPF（正电荷）制备中性、带负电荷或带正电荷的支架。为了研究不同BMP-2释放速率的表面电荷，通过蛋白质包封到聚（乳酸-共-乙醇酸）微球和/或吸附在OPF复合材料上产生三种BMP-2释放曲线。放射性标记的125 I-BMP-2在体外和体内的释放进行了分析，并在大鼠皮下植入9周后评估了骨形成。与中性和带正电的OPF相比，带负电的OPF产生更多的骨形成。对于所有三种加载方法和随后的BMP-2释放曲线都观察到这种效果。沿着电荷修饰，BMP-2的更持续释放改善了OPF复合材料中的整体骨形成。总的来说，这项研究清楚地表明，与OPF复合材料中的中性和正电荷相比，负电荷可以增强骨形成。Impact StatementBiomaterials在骨再生中可以发挥双重作用：它们能够局部持续输送生长因子，如骨形态发生蛋白-2（BMP-2），同时它们作为支架提供结构支撑。通过更好地模仿天然骨组织的特性，支架可以是骨传导性和骨诱导性的。后者可以通过改变表面的电荷来实现。目前的工作使用可调寡聚[（聚乙二醇）富马酸盐]水凝胶，并表明，负电荷增强BMP-2诱导的骨形成相比，中性或正电荷。总之，这表明生物材料的组织特异性表面电荷修饰在组织再生领域具有很大的前景。
Biomaterials that act as both protein delivery vehicle and scaffold can improve the safety and efficacy of bone morphogenetic protein-2 (BMP-2) for clinical applications. However, the optimal scaffold characteristics are not known. The osteoinductive and osteoconductive capacity of a fixed electrically charged surface is thus far unexplored. Therefore, in this study, we aim to investigate the effect of different electrical states on BMP-2-induced bone formation in oligo[(polyethylene glycol) fumarate] (OPF) hydrogels. Neutral, negatively, or positively charged scaffolds were fabricated using unmodified OPF (neutral charge), sodium methacrylate crosslinked OPF (negative charge), or [2-(methacryloyloxy) ethyl] trimethylammonium chloride crosslinked OPF (positive charge), respectively. To allow investigation of surface charge for different BMP-2 release rates, three BMP-2 release profiles were generated by protein encapsulation into poly(lactic-co-glycolic acid) microspheres and/or adsorption on the OPF composite. Release of radiolabeled125I-BMP-2 was analyzedin vitroandin vivoand bone formation was assessed after 9 weeks of subcutaneous implantation in rats. Negatively charged OPF generated significantly more bone formation compared with neutral and positively charged OPF. This effect was seen for all three loading methods and subsequent BMP-2 release profiles. Along with charge modifications, a more sustained release of BMP-2 improved overall bone formation in OPF composites. Overall, this study clearly shows that negative charge enhances bone formation compared with neutral and positive charge in OPF composites.Impact StatementBiomaterials can play a dual role in bone regeneration: they enable local sustained delivery of growth factors, such as bone morphogenetic protein-2 (BMP-2), while they provide structural support as scaffold. By better imitating the properties of native bone tissue, scaffolds may be both osteoconductive and osteoinductive. The latter can be achieved by modifying the electrical charge of the surface. The present work uses tunable oligo[(polyethylene glycol) fumarate] hydrogel and demonstrates that negative charge enhances BMP-2-induced bone formation compared with neutral or positive charge. Altogether, this indicates that tissue-specific surface charge modifications of biomaterials hold great promise in the field of tissue regeneration.