Xie Denghui, Guo Jinshan, Mehdizadeh Mohammadreza, Tran Richard T, Chen Ruisong, Sun Dawei, Qian Guoying, Jin Dadi, Bai Xiaochun, Yang Jian
Department of Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University; Academy of Orthopedics, Guangdong Province; Biology Department, Southern Medical University, Guangzhou, 510515, China ; Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
Department of Biomedical Engineering, Materials Research Institutes, The Huck Institutes of The Life Sciences, The Pennsylvania State University, University Park 16802, USA.
J Mater Chem B. 2015 Jan 21;3:387-398. doi: 10.1039/C4TB01498G.
Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2-4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF.
可注射骨植入物已广泛应用于骨组织修复，包括粉碎性骨折（CBF）的治疗。然而，大多数可注射骨植入物由于其较弱的组织粘附强度和最小的骨诱导性，并不适合治疗CBF。最近有报道称柠檬酸盐可通过增强生物陶瓷整合和骨诱导性来促进骨形成。在此，开发了一种新型的基于柠檬酸盐的贻贝启发式生物粘附羟基磷灰石（iCMBA/HA）骨替代物用于治疗CBF。iCMBA/HA可在2 - 4分钟内凝固，制备好的（湿的）iCMBA/HA具有低膨胀率、高达3.2±0.27 MPa的抗压机械强度、30天内完全降解、合适的生物相容性和骨诱导性。这也是首次证明在成骨培养基中添加柠檬酸盐以及iCMBA/HA降解释放的柠檬酸盐可促进成骨定向的人骨髓间充质干细胞（hMSCs）的矿化。在兔桡骨粉碎性骨折模型中对iCMBA/HA进行的体内评估显示，与阴性对照相比，骨形成显著增加，三点弯曲强度明显增强。还观察到了新血管形成、骨长入以及高度有序的骨形成，表明iCMBA/HA在治疗CBF方面具有潜力。
