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Controlled synthesis of mussel-inspired Ag nanoparticle coatings with demonstrated in vitro and in vivo antibacterial properties

2021, Wang, Xiaowei, Xu, Kehui, Cui, Wendi, Yang, Xi, Maitz, Manfred F., Li, Wei, Li, Xiangyang, Chen, Jialong

The in-situ formation of silver nanoparticles (AgNPs) via dopamine-reduction of Ag+ has been widely utilized for titanium implants to introduce antibacterial properties. In previous studies, the preparation of AgNPs has focused on controlling the feeding concentrations, while the pH of the reaction solution was ignored. Herein, we systematically determined the influence of various pH (4, 7, 10) and Ag+ concentrations (0.01, 0.1 mg/mL) on the AgNPs formation, followed by the evaluation of the antibacterial properties in vitro and in vivo. The results revealed that an alkaline environment was favourable for AgNP formation and resulted in more particles. Although the AgNPs bearing Ti had lower biocompatibilities, it was significantly improved after 7 days of mineralization in simulated body fluid. The outstanding antibacterial property of the AgNPs was well maintained after one day and seven days of implantation. Moreover, 3D micro-CT modelling showed that the pH 10/0.1 group exhibited remarkable osteogenesis, which may be due to their strong antibacterial properties and ability to promote mineralization. Therefore, we have demonstrated that the solution pH was as important as the feeding Ag+ concentration in determining AgNP formation, and it has paved the way for developing various AgNP-loaded surfaces that could meet different antibacterial needs.

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Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts

2019, Krieghoff, Jan, Picke, Ann-Kristin, Salbach-Hirsch, Juliane, Rother, Sandra, Heinemann, Christiane, Bernhardt, Ricardo, Kascholke, Christian, Möller, Stephanie, Rauner, Martina, Schnabelrauch, Matthias, Hintze, Vera, Scharnweber, Dieter, Schulz-Siegmund, Michaela, Hacker, Michael C., Hofbauer, Lorenz C., Hofbauer, Christine

Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial. Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by cross-polymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using student's t-test or two-way ANOVA. Results: We succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%. Conclusion: In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies. © 2019 The Author(s).