Dental caries is prevalent worldwide. Tooth cavity restorations cost more than $46 billion annually in the United States alone. The current generation of esthetic polymeric restorations have unsatisfactory failure rates. Replacing the failed restorations accounts for 50–70% of all the restorations. This article reviewed developments in producing a new generation of bioactive and therapeutic restorations. This includes: Protein-repellent and anti-caries polymeric dental composites, especially the use of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); protein-repellent adhesives to greatly reduce biofilm acids; bioactive cements to inhibit tooth lesions; combining protein-repellency with antibacterial nanoparticles of silver; tooth surface coatings containing calcium phosphate nanoparticles for remineralization; therapeutic restorations to suppress periodontal pathogens; and long-term durability of bioactive and therapeutic dental polymers. MPC was chosen due to its strong ability to repel proteins. DMAHDM was selected because it had the most potent antibacterial activity when compared to a series of antibacterial monomers. The new generation of materials possessed potent antibacterial functions against cariogenic and periodontal pathogens, and reduced biofilm colony-forming units by up to 4 logs, provided calcium phosphate ions for remineralization and strengthening of tooth structures, and raised biofilm pH from a cariogenic pH 4.5 to a safe pH 6.5. The new materials achieved a long-term durability that was significantly beyond current commercial control materials. This new generation of bioactive and nanostructured polymers is promising for wide applications to provide therapeutic healing effects and greater longevity for dental restorations.

Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo. hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC + hPDLSC-fibers + 0% Met (CPC + hPDLSCs + 0%Met); (3) CPC + hPDLSC-fibers + 0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC + hPDLSC-fibers + 0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC + hPDLSC-fibers + 0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation. The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p＜0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p＜0.05). Among all groups, CPC+hPDLSCs+ 0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5-10 folds those without Met (p＜0.05). Compared to CPC control, CPC+hPDLSCs+ 0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p＜0.05). The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+ 0.1%Met is highly promising for dental and craniofacial applications.

Objectives. The objective of this study is to develop a load-bearing prevascularized construct by combining calcium phosphate cement (CPC) with cells within a three-dimensional (3D) hydrogel culture system, to accelerate the regeneration of alveolar bone defects. Methods. A 3D co-culture system was established by encapsulating human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) within a gelatin methacryloyl (GelMA) hydrogel on 3D-printed porous CPC scaffolds. The mechanical properties, pore structure and angiogenic potency were determined in vitro. In vivo performance was evaluated using a nude rat subcutaneous implantation model and a rat alveolar bone defect model. Four groups were tested: (1) Blank group (surgery-only group); (2) CPC+GelMA group (non-prevascularized group)；(3) CPC+GelMA-cell group (prevascularized group)；(4) Natural Periodontiumgroup. Results. The novel construct had good mechanical properties and biocompatibility. The 3D co-culture in GelMA successfully induced microvascular formation in vitro. Subcutaneous implantation in nude rats showed that the CPC+GelMA-cell group exhibited markedly greater angiogenic capacity than the CPC+GelMA group after 6 weeks, with a neovascular density 1.93-fold higher than that of the non-prevascularized group. Among all groups, the CPC+GelMA-cell group exhibited the strongest capacity for repairing rat alveolar bone defects. Compared to CPC+GelMA group, CPC+GelMA-cell group significant enhanced bone regeneration in rats by 1.23-1.37 folds, and increased vascularization by 2.65 folds (p＜0.05). Conclusions: The novel three-dimensional prevascularized CPC construct combined appropriate mechanical properties with great efficacy for alveolar bone regeneration and vascularization in vivo in an animal model.

The objective of this study is to develop a load-bearing prevascularized construct by combining calcium phosphate cement (CPC) with cells within a three-dimensional (3D) hydrogel culture system, to accelerate the regeneration of alveolar bone defects. A 3D co-culture system was established by encapsulating human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) within a gelatin methacryloyl (GelMA) hydrogel on 3D-printed porous CPC scaffolds. The mechanical properties, pore structure and angiogenic potency were determined in vitro. In vivo performance was evaluated using a nude rat subcutaneous implantation model and a rat alveolar bone defect model. Four groups were tested: (1) Blank group (surgery-only group); (2) CPC+GelMA group (non-prevascularized group); (3) CPC+GelMA-cell group (prevascularized group)༛(4) Natural Periodontium group. The novel construct had good mechanical properties and biocompatibility. The 3D co-culture in GelMA successfully induced microvascular formation in vitro. Subcutaneous implantation in nude rats showed that the CPC+GelMA-cell group exhibited markedly greater angiogenic capacity than the CPC+GelMA group after 6 weeks, with a neovascular density 1.93-fold higher than that of the non-prevascularized group. Among all groups, the CPC+GelMA-cell group exhibited the strongest capacity for repairing rat alveolar bone defects. Compared to CPC+GelMA group, CPC+GelMA-cell group significant enhanced bone regeneration in rats by 1.23-1.37 folds, and increased vascularization by 2.65 folds (p<0.05). The novel 3D prevascularized CPC construct combined appropriate mechanical properties with great efficacy for alveolar bone regeneration and vascularization in vivo in an animal model.