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生物活性聚合物功能化Ti6Al4V表面诱导的骨组织反应:体外和体内研究

Bone tissue response induced by bioactive polymer functionalized Ti6Al4V surfaces: In vitro and in vivo study.

作者信息

Felgueiras Helena P, Decambron Adeline, Manassero Mathieu, Tulasne Louise, Evans Margaret D M, Viateau Véronique, Migonney Véronique

机构信息

Laboratory of Biomaterials and Polymers of Specialty, LBPS-CSPBAT CNRS UMR 7244, Université Paris 13, Sorbonne Paris Cité, 93430 Villetaneuse, France.

Laboratoire de Bioingénierie et Bioimagerie Ostéo-articulaires (B2OA), UMR 7052, Université Paris Diderot, 75010 Paris, France; École Nationale Vétérinaire d'Alfort, Service de Chirurgie, Université Paris Est, 94700 Maisons-Alfort, France.

出版信息

J Colloid Interface Sci. 2017 Apr 1;491:44-54. doi: 10.1016/j.jcis.2016.12.023. Epub 2016 Dec 18.

DOI:10.1016/j.jcis.2016.12.023
PMID:28012912
Abstract

Ti6Al4V is commonly used for orthopedic applications. This study was designed to test the potentially added benefit of Ti6Al4V functionalized with a bioactive polymer poly(sodium styrene sulfonate) both in vitro and in vivo. Cell-based assays with MC3T3-E1 osteoblast-like cells were used to measure the cell adhesion strength, cell spreading, focal contact formation, cell differentiation and the mineralization of extracellular matrix on grafted and ungrafted Ti6Al4V discs in combination with FBS and collagen type I. Bone morphogenetic protein-2 (BMP-2) was also included in the cell differentiation assay. Results showed that the grafted surface combined with collagen I gave superior levels in every parameter tested with cell-based assays and was almost equivalent to BMP-2 for cell differentiation. In vivo testing was conducted in rabbits (n=42) with cylinders of grafted and ungrafted Ti6Al4V implanted in defects made to the femoral and lateral condyles and animals that were maintained to 1, 3 and 12months. Hydroxyapatite coated Ti6Al4V cylinders were included as a clinical reference control. Osseointegration was assessed post-mortem using histomorphometric analysis conducted on resin sections of explanted undecalcified bone. Two histomorphometric parameters, that of bone-to-implant contact and the bone area, were analyzed by a trained observer blinded to sample identity. Results showed osseointegration on grafted Ti6Al4V was marginally better than both ungrafted and hydroxyapatite coated Ti6Al4V. Overall, the study found that the grafted Ti6Al4V significantly promoted all aspects of osteogenesis tested in vitro and, although in vivo outcomes were less compelling, histomorphometry showed osseointegration of grafted Ti6Al4V implants was equivalent or better than controls.

摘要

Ti6Al4V常用于骨科应用。本研究旨在测试用生物活性聚合物聚(苯乙烯磺酸钠)功能化的Ti6Al4V在体外和体内的潜在附加益处。使用MC3T3-E1成骨样细胞进行基于细胞的测定,以测量在添加胎牛血清(FBS)和I型胶原蛋白的情况下,接种和未接种Ti6Al4V圆盘上的细胞粘附强度、细胞铺展、粘着斑形成、细胞分化以及细胞外基质矿化情况。细胞分化测定中还加入了骨形态发生蛋白-2(BMP-2)。结果表明,接种表面与I型胶原蛋白结合后,在基于细胞的测定中所测试的每个参数上都给出了更高的水平,并且在细胞分化方面几乎与BMP-2相当。在兔子(n = 42)身上进行体内测试,将接种和未接种的Ti6Al4V圆柱体植入股骨和外侧髁的缺损处,并将动物饲养1、3和12个月。羟基磷灰石涂层的Ti6Al4V圆柱体作为临床参考对照。在取出的未脱钙骨的树脂切片上进行组织形态计量分析,以评估死后的骨整合情况。由对样本身份不知情的训练有素的观察者分析两个组织形态计量参数,即骨与植入物接触面积和骨面积。结果表明,接种的Ti6Al4V的骨整合略优于未接种和羟基磷灰石涂层的Ti6Al4V。总体而言,该研究发现,接种的Ti6Al4V在体外显著促进了所测试的成骨的各个方面,尽管体内结果不太令人信服,但组织形态计量学显示接种的Ti6Al4V植入物的骨整合与对照相当或更好。

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