期刊
BIOFABRICATION
卷 12, 期 3, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/1758-5090/ab906e
关键词
tissue engineering; vascularization; craniomaxillofacial reconstruction; Osteogenesis
资金
- Mary & Dick Holland Regenerative Medicine Program
- University of Nebraska Collaboration Initiative Seed Grant
- China Scholarship Council
- Nebraska Research Initiative
- Fred and Pamela Buffett Cancer Center Support Grant [P30CA036727]
- Institutional Development Award (IDeA) from the NIGMS of the NIH [P30GM106397]
- University of Nebraska Foundation
- NIH [R01 AR073225, R21AI140026]
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 promotedin vivomandibular 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.
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