Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, Xueyuan West Road, Lucheng District, Wenzhou 325000, Zhejiang Province, People's Republic of China. These authors contributed equally to this work.
Biomed Mater. 2020 Jun 16;15(4):045011. doi: 10.1088/1748-605X/ab7b3d.
Osteoporosis is a severe health problem causing bone fragility and consequent fracture. Titanium (Ti) implants, used in patients with osteoporotic fractures, are prone to failure because of the decreased bone mass and strength. Therefore, it is of utmost importance to fabricate implants possessing osteogenic properties to improve implant osseointegration. To improve the long-term survival rate of Ti implants in osteoporotic patients, hyaluronic acid/ϵ-polylysine multilayers containing the parathyroid hormone (PTH)-related protein (PTHrP) were deposited on Ti implants by a layer-by-layer (LBL) electro assembly technique. The murine pre-osteoblast cell line MC3T3-E1, possessing a high potential of osteoblast differentiation, was used to evaluate the osteo-inductive effects of Ti-LBL-PTHrP in vitro. In addition, the performance of the Ti (Ti-LBL-PTHrP) implant was evaluated in vivo in a femoral intramedullary implantation in Sprague Dawley rats. The Ti-LBL-PTHrP implant regulated the release of the loaded PTHrP to increase bone formation in the early stage of implantation. The in vitro results revealed that cells on Ti-LBL-PTHrP did not show any evident proliferation, but a high level of alkaline phosphatase activity and osteoblast-related protein expression was found, compared to the uncoated Ti group (p < 0.05). In addition, in vivo micro-CT and histological analysis demonstrated that the Ti-LBL-PTHrP implants could significantly promote the formation and remodeling of new bone in osteoporotic rats at 14 d after implantation. Overall, this study established a profound and straightforward methodology for the manufacture of biofunctional Ti implants for the treatment of osteoporosis.
骨质疏松症是一种严重的健康问题，会导致骨骼脆弱和随之而来的骨折。在骨质疏松性骨折患者中使用的钛（Ti）植入物由于骨量和强度的减少而容易失效。因此，制造具有成骨特性的植入物以改善植入物的骨整合至关重要。为了提高骨质疏松症患者中 Ti 植入物的长期存活率，通过层层（LBL）电组装技术在 Ti 植入物上沉积了含有甲状旁腺激素（PTH）相关蛋白（PTHrP）的透明质酸/ε-聚赖氨酸多层。使用具有高成骨细胞分化潜力的鼠前成骨细胞系 MC3T3-E1 在体外评估 Ti-LBL-PTHrP 的诱导成骨作用。此外，还在 Sprague Dawley 大鼠股骨髓内植入物中评估了 Ti（Ti-LBL-PTHrP）植入物的体内性能。Ti-LBL-PTHrP 植入物调节了加载的 PTHrP 的释放，以增加植入早期的骨形成。体外结果表明，与未涂层的 Ti 组相比，Ti-LBL-PTHrP 上的细胞没有明显的增殖，但发现碱性磷酸酶活性和骨细胞相关蛋白表达水平较高（p < 0.05）。此外，体内 micro-CT 和组织学分析表明，Ti-LBL-PTHrP 植入物在植入后 14 天可以显著促进骨质疏松大鼠新骨的形成和重塑。总体而言，这项研究为治疗骨质疏松症的生物功能 Ti 植入物的制造建立了一种深刻而直接的方法。
