School of Medical science and Technology, IIT Kharagpur, Kharagpur, West Bengal Pin code-721302, India.
Dr. B. C. Roy Technology Hospital, IIT Kharagpur, Kharagpur, West Bengal Pin code-721302, India.
Biomed Mater. 2020 Nov 21;15(6):064102. doi: 10.1088/1748-605X/abb12b.
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.
疏水性药物分子在固定于超疏水金属表面（如传统钛植入物）方面存在重大挑战。预先涂覆的表面改性可能会提供更好的平台，改善润湿性，以达到这种目的。如本研究所述，这种改性被假设为提供必要的粗糙度，以帮助聚合物（如丝素蛋白（SF））的沉积作为药物结合基质，此外还可以显著改善早期蛋白质吸附，从而促进更快的细胞黏附和增殖。在钛表面上开发了一种基于丝的局部药物输送模块，并对其表面粗糙度、润湿性、生物相容性以及在涂覆金属表面上培养的细胞的体外分化潜力进行了测试，这些表面涂覆了 Tibolone 的活性代谢物。用成骨和破骨细胞培养基对基质涂层植入物进行条件处理，并补充 Tibolone，刺激了早期成骨基因的表达和细胞外基质中的钙沉积。在存在药物的情况下，还观察到对吸收活性的显著抑制。为了评估通过拓扑改性钛植入物局部递送 Tibolone 诱导早期种植体周围骨形成的效果，在接受双侧卵巢切除术的大鼠中人为诱导骨质疏松症，然后放置植入物。骨质疏松大鼠通过仿生基质中 Tibolone 的骨特异性释放表明，在 2 周和 4 周后（与假涂层植入物相比，p < 0.05），种植体周围骨生长有显著改善。这些发现首次表明，从 SF 基质涂层植入物释放的 Tibolone 可以加速骨固定器的生物学稳定性。
