Departments of Orthopedic Surgery, Clinical Laboratory Medicine, Breast Surgery, Burn and Plastic Surgery, Otolaryngology-Head and Neck Surgery, and Obstetrics and Gynecology , the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016 , China.
Institute for Molecular Engineering , The University of Chicago , Chicago , Illinois 60637 , United States.
ACS Appl Mater Interfaces. 2019 Mar 6;11(9):8749-8762. doi: 10.1021/acsami.8b19094. Epub 2019 Feb 25.
Effective bone tissue engineering can restore bone and skeletal functions that are impaired by traumas and/or certain medical conditions. Bone is a complex tissue and functions through orchestrated interactions between cells, biomechanical forces, and biofactors. To identify ideal scaffold materials for effective mesenchymal stem cell (MSC)-based bone tissue regeneration, here we develop and characterize a composite nanoparticle hydrogel by combining carboxymethyl chitosan (CMCh) and amorphous calcium phosphate (ACP) (designated as CMCh-ACP hydrogel). We demonstrate that the CMCh-ACP hydrogel is readily prepared by incorporating glucono δ-lactone (GDL) into an aqueous dispersion or rehydrating the acidic freeze-dried nanoparticles in a pH-triggered controlled-assembly fashion. The CMCh-ACP hydrogel exhibits excellent biocompatibility and effectively supports MSC proliferation and cell adhesion. Moreover, while augmenting BMP9-induced osteogenic differentiation, the CMCh-ACP hydrogel itself is osteoinductive and induces the expression of osteoblastic regulators and bone markers in MSCs in vitro. The CMCh-ACP scaffold markedly enhances the efficiency and maturity of BMP9-induced bone formation in vivo, while suppressing bone resorption occurred in long-term ectopic osteogenesis. Thus, these results suggest that the pH-responsive self-assembled CMCh-ACP injectable and bioprintable hydrogel may be further exploited as a novel scaffold for osteoprogenitor-cell-based bone tissue regeneration.
有效的骨组织工程可以恢复因创伤和/或某些疾病而受损的骨骼功能。骨骼是一种复杂的组织，通过细胞、生物力学和生物因素的协调相互作用发挥功能。为了确定用于有效的间充质干细胞（MSC）为基础的骨组织再生的理想支架材料，我们在此开发并表征了一种通过将羧甲基壳聚糖（CMCh）和无定形磷酸钙（ACP）结合在一起（命名为 CMCh-ACP 水凝胶）的复合纳米颗粒水凝胶。我们证明，CMCh-ACP 水凝胶可以通过将葡庚糖内酯（GDL）掺入水性分散体中或通过在 pH 触发的受控组装方式中重新水合酸性冻干纳米颗粒来容易地制备。CMCh-ACP 水凝胶具有出色的生物相容性，可有效支持 MSC 的增殖和细胞黏附。此外，在增强 BMP9 诱导的成骨分化的同时，CMCh-ACP 水凝胶本身具有成骨性，并在体外诱导 MSC 中成骨细胞调节剂和骨标志物的表达。CMCh-ACP 支架显著提高了 BMP9 诱导的体内骨形成的效率和成熟度，同时抑制了异位成骨中长期发生的骨质吸收。因此，这些结果表明，pH 响应性自组装的 CMCh-ACP 可注射和生物可打印水凝胶可进一步开发为基于成骨前体细胞的骨组织再生的新型支架。
