Functionalization of scaffolds with chimeric anti-BMP-2 monoclonal antibodies for osseous regeneration.

Functionalization of scaffolds with chimeric anti-BMP-2 monoclonal antibodies for osseous regeneration.
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DOI:
10.1016/j.biomaterials.2013.08.069
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发表时间:
2013-12
期刊:
影响因子:
14
通讯作者:
Zadeh, Homayoun H.
Zadeh, Homayoun H.
中科院分区:
工程技术1区
文献类型:
--
作者:
Ansari, Sahar;Moshaverinia, Alireza;Pi, Sung Hee;Han, Alexander;Abdelhamid, Alaa I.;Zadeh, Homayoun H.

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最近的研究已经证明了固定在可吸收胶原海绵(ACS)上的鼠抗BMP-2单克隆抗体(mAb)介导从头骨形成的能力,该过程称为抗体介导的骨再生(AMOR)。本研究的目的是评估新产生的嵌合抗BMP-2单克隆抗体在介导AMOR中的功效,以及评估不同生物材料作为支架参与AMOR的适用性。将嵌合抗BMP-2单克隆抗体固定在钛微珠(Ti)、藻酸盐水凝胶、大孔双相磷酸钙(MBCP)和ACS 4种生物材料上,然后植入大鼠颅骨缺损。8周后处死动物,使用显微CT和组织形态计量学评估骨填充程度。结果表明嵌合抗BMP-2 mAb的局部持久性长达8周,以及在植入固定在4种支架中的每一种上的嵌合抗BMP-2抗体的部位中显著的从头骨再生。Ti和MBCP显示出最高的骨再生量,可能是由于其抗压缩性。藻酸盐和ACS也介导了新生骨形成,尽管观察到显著的体积收缩。体外试验证明了嵌合抗BMP-2 mAb与BMP-4和BMP-7的交叉反应性。抗BMP-2单克隆抗体与BMP-2免疫复合物诱导C2 C12细胞体外成骨分化,涉及RUNX 2表达和Smad 1磷酸化。目前的数据证明了嵌合抗BMP-2 mAb功能化具有不同特征的不同生物材料以介导骨生成的能力。
Recent studies have demonstrated the ability of murine anti-BMP-2 monoclonal antibodies (mAb) immobilized on an absorbable collagen sponge (ACS) to mediate de novo bone formation, a process termed antibody mediated osseous regeneration (AMOR). The objectives of this study were to assess the efficacy of a newly generated chimeric anti-BMP-2 mAb in mediating AMOR, as well as to evaluate the suitability of different biomaterials as scaffolds to participate in AMOR. Chimeric anti-BMP-2 mAb was immobilized on 4 biomaterials, namely, titanium microbeads (Ti), alginate hydrogel, macroporous biphasic calcium phosphate (MBCP) and ACS, followed by surgical implantation into rat critical-size calvarial defects. Animals were sacrificed after 8 weeks and the degree of bone fill was assessed using micro-CT and histomorphometry. Results demonstrated local persistence of chimeric anti-BMP-2 mAb up to 8 weeks, as well as significant de novo bone regeneration in sites implanted with chimeric anti-BMP-2 antibody immobilized on each of the 4 scaffolds. Ti and MBCP showed the highest volume of bone regeneration, presumably due to their resistance to compression. Alginate and ACS also mediated de novo bone formation, though significant volumetric shrinkage was noted. In vitro assays demonstrated cross-reactivity of chimeric anti-BMP-2 mAb with BMP-4 and BMP-7. Immune complex of anti-BMP-2 mAb with BMP-2 induced osteogenic differentiation of C2C12 cells in vitro, involving expression of RUNX2 and phosphorylation of Smad1. The present data demonstrated the ability of chimeric anti- BMP-2 mAb to functionalize different biomaterial with varying characteristics to mediate osteogenesis.
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发表时间: 2011-05-01
期刊: THERIOGENOLOGY
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期刊: GROWTH FACTORS
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