Biomaterials Field, Research Center for Functional Materials , National Institute for Materials Science , 1-1 Namiki , Tsukuba , Ibaraki 305-0044 , Japan.
Biomacromolecules. 2019 Mar 11;20(3):1385-1393. doi: 10.1021/acs.biomac.8b01767. Epub 2019 Feb 25.
An injectable bone may serve as a minimally invasive therapy for large orthopedic defects and osteoporosis and an alternative to allografting and surgical treatment. However, conventional bone substitutes lack the desirable biodegradability, bioresponsibility, and functionality to regulate the bone regeneration process. Here, we report an injectable, bioresponsive bone composed of bisphosphonate-modified nanocellulose (pNC) as a bone substitute for bone regeneration. Composites composed of nanofibrillated cellulose and β-tricalcium phosphate (β-TCP) mimic bone structures in which apatite reinforces collagen fibrils. Bisphosphonate groups on nanocellulose provide reversible, physical cross-linking with β-TCP, apatite formation, binding property to bone, and pH responsiveness. When the pH drops to ∼4.5, which corresponds to an osteoclast-induced pH decrease, pNC-β-TCP composite degrades and releases pNC. pNC suppresses osteoclast formation and pit formation. This osteoclast-responsive property allows for controlling the degradation rate of the composite. Moreover, the composite of pNC, α-tricalcium phosphate (α-TCP), and β-TCP enhances osteoblast differentiation. This injectable bone substitute of pNC that regulates osteoclast/osteoblast activity has enormous potential for the treatment of bone diseases and prevention of locomotive syndrome.
可注射骨可作为治疗大骨科缺陷和骨质疏松症的微创疗法，也可替代同种异体移植物和手术治疗。然而，传统的骨替代物缺乏理想的生物降解性、生物响应性和功能性，无法调节骨再生过程。在这里，我们报告了一种可注射的、生物响应性的骨，由双膦酸盐修饰的纳米纤维素 (pNC) 组成，作为骨再生的骨替代物。由纳米原纤维纤维素和 β-磷酸三钙 (β-TCP) 组成的复合材料模拟了骨结构，其中磷灰石增强了胶原纤维。纳米纤维素上的双膦酸盐基团提供了与 β-TCP、磷灰石形成、与骨结合的可逆物理交联以及 pH 响应性。当 pH 值下降到约 4.5 时，对应于破骨细胞诱导的 pH 值下降，pNC-β-TCP 复合材料降解并释放 pNC。pNC 抑制破骨细胞的形成和凹陷的形成。这种破骨细胞响应性特性允许控制复合材料的降解速率。此外，pNC、α-磷酸三钙 (α-TCP) 和 β-TCP 的复合材料增强成骨细胞分化。这种可注射的 pNC 骨替代物可调节破骨细胞/成骨细胞的活性，对治疗骨疾病和预防运动障碍综合征具有巨大潜力。
