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Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo
Biomedical Materials ( IF 4 ) Pub Date : 2020-11-21 , DOI: 10.1088/1748-605x/abb12b
Anwesha Barik 1 , Suman Kumar Ray 1 , Prasanna Kumar Byram 1 , Rashmi Sinha 2, 3 , Nishant Chakravorty 1
Affiliation  

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.



中文翻译:

骨质疏松大鼠模型中前成骨细胞的广泛早期矿化、破骨细胞生成的抑制和更快的种植体周围骨愈合:体外和体内评估的替勃龙骨特异性递送的主要有效性

疏水药物分子在固定在超疏水金属表面(如常规钛植入物)上提出了重大挑战。为此目的,预涂层表面改性可以产生具有改进润湿性的更好平台。正如本研究中所描述的,这些修饰被假设为提供必要的粗糙度,以帮助像丝素蛋白 (SF) 这样的聚合物沉积作为药物结合基质,此外还显着改善早期蛋白质吸附,从而促进更快的细胞粘附和增殖. 在钛表面上开发了一种基于丝绸的局部给药模块,并对其表面粗糙度、润湿性、生物相容性和体外进行了测试在有/没有外部补充替勃龙活性代谢物的情况下,在涂覆的金属表面上培养的细胞的分化潜能。用添加替勃龙的成骨培养基和破骨培养基对基质涂层植入物进行调理刺激了早期成骨基因的表达和细胞外基质中的钙沉积。在药物存在下也观察到吸收活性的显着抑制。为了评估通过拓扑修饰的钛植入物局部递送替勃龙以诱导早期植入物周围骨形成的功效,在进行双侧卵巢切除术的大鼠中人工诱导骨质疏松症,然后放置植入物。与假涂层植入物相比,p < 0.05)。这些发现首次表明,SF 基质涂层植入物释放的替勃龙可以加速骨固定物的生物稳定性。

更新日期:2020-11-21
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