First Hip Department of Orthopedics, Tianjin Hospital, Tianjin 300211, People's Republic of China. Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, United States of America. Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America.
Biofabrication. 2020 Jun 12;12(3):035020. doi: 10.1088/1758-5090/ab906e.
Functional reconstruction of craniomaxillofacial defects is challenging, especially for the patients who suffer from traumatic injury, cranioplasty, and oncologic surgery. Three-dimensional (3D) printing/bioprinting technologies provide a promising tool to fabricate bone tissue engineering constructs with complex architectures and bioactive components. In this study, we implemented multi-material 3D printing to fabricate 3D printed PCL/hydrogel composite scaffolds loaded with dual bioactive small molecules (i.e. resveratrol and strontium ranelate). The incorporated small molecules are expected to target several types of bone cells. We systematically studied the scaffold morphologies and small molecule release profiles. We then investigated the effects of the released small molecules from the drug loaded scaffolds on the behavior and differentiation of mesenchymal stem cells (MSCs), monocyte-derived osteoclasts, and endothelial cells. The 3D printed scaffolds, with and without small molecules, were further implanted into a rat model with a critical-sized mandibular bone defect. We found that the bone scaffolds containing the dual small molecules had combinational advantages in enhancing angiogenesis and inhibiting osteoclast activities, and they synergistically promoted MSC osteogenic differentiation. The dual drug loaded scaffolds also significantly promoted in vivo mandibular bone formation after 8 week implantation. This work presents a 3D printing strategy to fabricate engineered bone constructs, which can likely be used as off-the-shelf products to promote craniomaxillofacial regeneration.
颅颌面缺损的功能重建具有挑战性，特别是对于创伤、颅骨修复和肿瘤手术患者。三维（3D）打印/生物打印技术为制造具有复杂结构和生物活性成分的骨组织工程构建体提供了有前途的工具。在这项研究中，我们实施了多材料 3D 打印来制造负载双生物活性小分子（即白藜芦醇和雷奈酸锶）的 3D 打印 PCL/水凝胶复合支架。预期掺入的小分子可以靶向几种类型的骨细胞。我们系统地研究了支架形态和小分子释放曲线。然后，我们研究了载药支架释放的小分子对间充质干细胞（MSCs）、单核细胞来源的破骨细胞和成血管细胞行为和分化的影响。进一步将具有和不具有小分子的 3D 打印支架植入具有临界尺寸下颌骨缺损的大鼠模型中。我们发现，含有双小分子的骨支架在促进血管生成和抑制破骨细胞活性方面具有组合优势，并且它们协同促进 MSC 成骨分化。双药物负载支架在植入 8 周后也显著促进了体内下颌骨形成。这项工作提出了一种 3D 打印策略来制造工程化骨构建体，这些构建体可能用作现成产品来促进颅颌面再生。
