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Abstract In this work, a tumor microenvironment (TME)-responsive biodegradable MnSiO 3 @Fe 3 O 4 nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe 3 O 4 nanoparticles decorated on the surface of MnSiO 3 could effectively obstruct the pores of MnSiO 3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe 3 O 4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe 3 O 4 and released Mn2+ can help reduce the interference between their T 1 and T 2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe 3 O 4 nanocrystals, the catalytic activity of the Fe 3 O 4 nanocrystals toward a Fenton-like reaction within cancer cells could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T 1 -T 2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy. Graphical abstract A multifunctional MnSiO 3 @Fe 3 O 4 nanoplatform is constructed by decorating Fe 3 O 4 nanoparticles on the surface of MnSiO 3 , followed by amination and grafting PEG on the surface and subsequently loading cisplatin into the nanoplatform. This well-engineered nanoplatform with tumor microenvironment-responsive biodegradable ability displays outstanding dual-mode MRI-guided combinatorial catalytic nanotherapeutics (the generation of ·OH) and chemotherapy for cancer treatment. Image 1 [ABSTRACT FROM AUTHOR]

Abstract: Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF165) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF165 and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF165 (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF165/BMP-2 (group V + B) (n = 6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF165 promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V + B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V + B were larger than those of the Silk gel and VEGF groups, and the V + B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V + B. In conclusion, VEGF165 and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities. [Copyright &y& Elsevier]

A tissue-engineered bone has become a viable alternative to autologous bone for bone augmentation in atrophy alveolar ridge. The aim of the present study was to evaluate porous beta-tricalcium phosphate (beta-TCP) combined with autologous osteoblasts to augment edentulous alveolar ridge in a canine model. Autologous osteoblasts were expanded and combined with beta-TCP scaffold to fabricate a tissue-engineered bone. 12 bilateral alveolar ridge augmentation surgeries were carried out in 6 beagle dogs with the following 3 groups: beta-TCP/osteoblasts, beta-TCP alone and autogenous iliac bone control (n=4 per group). Sequential fluorescent labeling and radiographs were used to compare new bone formation and mineralization in each group. 24 weeks later, animals were sacrificed and non-decalcified and decalcified sections were evaluated histologically and histomorphometrically. Results indicated that the tissue-engineered bone dramatically enhanced new bone formation and mineralization, increase the new bone area, and maintain the height and thickness of the augmented alveolar ridge when compared with beta-TCP alone group. More importantly, the tissue-engineered bone achieved an elevated bone height and thickness comparable to that of autogenous iliac bone graft. This study demonstrated the potential of porous beta-TCP as a substrate for autogenous osteoblasts in bone tissue engineering for alveolar ridge augmentation.