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通过寡核苷酸介导的骨形态发生蛋白-2固定化改善骨质疏松大鼠中Ti6Al4V骨科骨植入物的锚固

Improved anchorage of Ti6Al4V orthopaedic bone implants through oligonucleotide mediated immobilization of BMP-2 in osteoporotic rats.

作者信息

Wölfle Julia V, Fiedler Jörg, Dürselen Lutz, Reichert Judith, Scharnweber Dieter, Förster Anne, Schwenzer Bernd, Reichel Heiko, Ignatius Anita, Brenner Rolf E

机构信息

Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.

Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.

出版信息

PLoS One. 2014 Jan 21;9(1):e86151. doi: 10.1371/journal.pone.0086151. eCollection 2014.

Abstract

The aim of the present study was to test the biocompatibility and functionality of orthopaedic bone implants with immobilized oligonucleotides serving as anchor stands for rhBMP-2 and rhVEGF-A conjugated with complementary oligonucleotides in an osteoporotic rat model. Al2O3-blasted acid etched Ti6Al4V implants, carrying oligonucleotide anchor strands and hybridized with rhBMP-2 or rhVEGF-A through complementary 31-mer oligonucleotide stands were inserted into the proximal tibia of ovariectomized rats. At the time of surgery (15 weeks after ovariectomy) microCT analysis showed significantly lower bone mineral density compared to non-ovariectomized animals. Bone-implant contact (BIC) and pullout-force were not negatively affected by non-hybridized anchor strands. Twelve weeks after surgery, a significantly higher pullout force was found for BMP-2 hybridized to the anchor strands compared to non-hybridized anchor strands or native samples, and on histomorphometric analysis BIC was highest in the BMP group. Thus, we could show the biocompatibility and in vivo functionality of this modular, self-organizing system for immobilization and subsequent release of BMP-2 in vivo.

摘要

本研究的目的是在骨质疏松大鼠模型中,测试作为rhBMP-2和rhVEGF-A锚定支架的固定化寡核苷酸与互补寡核苷酸缀合的骨科骨植入物的生物相容性和功能。将携带寡核苷酸锚定链并通过互补的31聚体寡核苷酸链与rhBMP-2或rhVEGF-A杂交的Al2O3喷砂酸蚀Ti6Al4V植入物插入去卵巢大鼠的胫骨近端。手术时(去卵巢15周后),与未去卵巢的动物相比,microCT分析显示骨矿物质密度显著降低。未杂交的锚定链对骨-植入物接触(BIC)和拔出力没有负面影响。术后12周,与未杂交的锚定链或天然样品相比,与锚定链杂交的BMP-2的拔出力显著更高,并且在组织形态计量分析中,BMP组的BIC最高。因此,我们可以证明这种模块化、自组织系统在体内固定和随后释放BMP-2的生物相容性和体内功能。

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