Controlled co-delivery system of magnesium and lanthanum ions for vascularized bone regeneration.

For craniofacial bone regeneration, how to promote vascularized bone regeneration is still a significant problem, and the controlled release of trace elements vital to osteogenesis has attracted attention. In this study, an ion co-delivery system was developed to promote angiogenesis and osteogenesis. Magnesium ions (Mg2+) and lanthanum ions (La3+) were selected as biosignal molecules because Mg2+can promote angiogenesis and both of them can enhance bone formation. Microspheres made of poly(lactide-co-glycolide) were applied to load La2(CO3)3, which was embedded into a MgO/MgCO3-loaded cryogel made of photocrosslinkable gelatin methacryloyl to enable co-delivery of Mg2+and La3+. Evaluations of angiogenesis and osteogenesis were conducted via bothin vitrocell culture using human bone marrow mesenchymal stromal cells andin vivoimplantation using a rat model with calvarial defect (5 mm in diameter). Compared to systems releasing only Mg2+or La3+, the combination system demonstrated more significant effects on blood vessels formation, thereby promoting the regeneration of vascularized bone tissue. At 8 weeks post-implantation, the new bone volume/total bone volume ratio reached a value of 40.1 ± 0.9%. In summary, a properly designed scaffold system with the capacity to release ions of different bioactivities in a desired pattern can be a promising strategy to meet vascularized bone regeneration requirements.

Injectable GelMA Cryogel Microspheres for Modularized Cell Delivery and Potential Vascularized Bone Regeneration.

Cell therapeutics hold tremendous regenerative potential and the therapeutic effect depends on the effective delivery of cells. However, current cell delivery carriers with unsuitable cytocompatibility and topological structure demonstrate poor cell viability during injection. Therefore, porous shape-memory cryogel microspheres (CMS) are prepared from methacrylated gelatin (GelMA) by combining an emulsion technique with gradient-cooling cryogelation. Pore sizes of the CMS are adjusted via the gradient-cooling procedure, with the optimized pore size (15.5 ± 6.0 µm) being achieved on the 30-min gradient-cooled variant (CMS-30). Unlike hydrogel microspheres (HMS), CMS promotes human bone marrow stromal cell (hBMSC) and human umbilical vein endothelial cell (HUVEC) adhesion, proliferated with high levels of stemness for 7 d, and protects cells during the injection process using a 26G syringe needle. Moreover, CMS-30 enhances the osteogenic differentiation of hBMSCs in osteoinductive media. CMS can serve as building blocks for delivering multiple cell types. Here, hBMSC-loaded and HUVEC-loaded CMS-30, mixed at a 1:1 ratio, are injected subcutaneously into nude mice for 2 months. Results show the development of vascularized bone-like tissue with high levels of OCN and CD31. These findings indicate that GelMA CMS of a certain pore size can effectively deliver multiple cells to achieve functional tissue regeneration.

Radiographic and Histologic Evaluation of Experimentally Induced Severe Intrusive Luxation of Immature Teeth in Rats.

INTRODUCTION: The aim of this study was to establish an intrusive luxation model in rats and observe the pulpal and periodontal outcomes. METHODS: The intrusion was experimentally induced by an application of 20-N force on the occlusal surface of maxillary right second molar along the tooth axial using a striking instrument in 3-week-old male Sprague-Dawley rats. Thirty rats were divided into 6 groups (n = 5) and were sacrificed after 3, 7, 14, 30, 60, and 90 days of the surgery. The occurrence of pulpal and periodontal complications was observed by micro-computed tomographic scanning and hematoxylin-eosin staining. RESULTS: All experimental teeth were fully intruded into the alveolar bone with their occlusal surface located at the cervical level of the adjacent first molar. Spontaneous re-eruption initiated at 7 days. At 14 days, 4 teeth (80%, 4/5) partially re-erupted, whereas 2 (40%), 3 (75%), and 4 (100%) teeth completely re-erupted at 30, 60, and 90 days, respectively. Pulp degeneration and inflammation mainly occurred in 4 teeth at 3 days, 5 at 7 days, and 2 at 14 days; after 14 days, pulp calcification was observed in 8 teeth. Ankylosis and replacement root resorption mainly occurred in 1 tooth at 30 days, 2 teeth at 60 days, and 3 at 90 days. Marginal bone loss was observed in 3 teeth (60%) at 30 days, 3 (75%) at 60 days, and 2 (50%) at 90 days. CONCLUSIONS: An animal model of intrusive dentoalveolar trauma was successfully established in rats. Pulpal and periodontal complications similar to clinical tooth intrusion were observed, which provided a basis for exploring the mechanisms of complications in the future.