Therapeutic ions, such as Si and Mg, play vital roles in regulating metabolism and promoting tissue repair, hence providing an efficient strategy in tissue engineering. The regenerative outcome is strongly dependent on the targeted delivery and controlled release of therapeutic ions. Nevertheless, it remains challenging to deliver multiple ions at controlled manners and ratios. Herein, hierarchical therapeutic ion‐based microspheres are fabricated. The coordinated release of Mg and Si ions at pre‐set ratios is achieved, based on which, Mg favors osteogenesis by inducing highly efficient cell recruitment and angiogenesis, and Si promotes massive collagen secretion and biomineralization to accelerate the bone maturation process. These therapeutic ion‐based microspheres (namely PNM2) can steadily release Mg and Si ions at an optimized ratio of 2:1, which shows the most significant synergistic effect on angiogenesis and osteogenesis. Furthermore, in a rat calvarial defects model, the volume and maturity of the vascularized neo‐bone tissue regenerated with PNM2 microspheres are comparable with or even surpassing those defects regenerated with growth factors and/or cell‐laden scaffolds. Overall, this platform provides a controllable strategy for the coordinated delivery of Mg/Si ions, opening a new avenue for developing therapeutic ion‐based microscaffold for tissue engineering.
This study intends to improve the antibacterial and mineralization performance of photocurable dental resin composites (DRCs) to reduce the possibility of repair failure caused by secondary caries. To the end, functionalized hydroxyapatite (HAp), including Zn-doped (Zn/HAp) and Sr-doped HAp (Sr/HAp), were added into the bisphenol A glycidyl methacrylate and triethylene glycol dimethacrylate mixture, providing the DRCs with antibacterial and mineralization capacity, respectively. By controlling the total amount of inorganic filler at 70 wt%, these HAp powders were introduced into the resin matrix with barium glass powder (BaGP), while the ratios of HAp to aGP varied from 0:70 to 8:62. And the 8 wt% of HAp could be pure HAp, Zn/HAp, Sr/HAp, or Zn/HAp +Sr/HAp in different ratios (i.e. 2:6, 4:4, 6:2). Though the fillers varied, the obtained DRCs displayed similar micro-morphology, flexural strength (∼110 MPa) and modulus (∼7 GPa), and Vickers hardness (∼65). When the doping amounts of Sr2+/Zn2+ reached 15 mol% of Ca2+ in the Sr/HAp and Zn/HAp, the DRCs displayed a high antibacterial activity by killing ∼95% Staphylococcus aureus, and induced rich mineral deposition on surface in simulated body fluid. The incorporation of the Zn/HAp and Sr/HAp into the DRCs did not cause significant cytotoxicity, with L929 fibroblasts remaining >99% viability as cultured in extracts made from the DRCs. Therein, the DRC preparations containing both Zn/HAp and Sr/HAp have achieved improvements in both the biomineralization and antibacterial performance, as well as, having sufficient mechanical properties and excellent biocompatibility for dental restoration.
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