ROS-Targeted Depression Therapy via BSA-Incubated Ceria Nanoclusters.

Depression is one of the most fatal mental diseases, and there is currently a lack of efficient drugs for the treatment of depression. Emerging evidence has indicated oxidative stress as a key pathological feature of depression. We targeted reactive oxygen species (ROS) and synthesized CeO2@BSA nanoclusters as a novel antidepression nanodrug via a convenient, green, and highly effective bovine serum albumin (BSA) incubation strategy. CeO2@BSA has ultrasmall size (2 nm) with outstanding ROS scavenging and blood-brain barrier crossing capacity, rapid metabolism, and negligible adverse effects in vitro and in vivo. CeO2@BSA administration alleviates depressive behaviors and depression-related pathological changes of the chronic restraint stress-induced depressive model, suggesting promising therapeutic effects of CeO2@BSA for the treatment of depression. Our study proved the validity by directly using nanodrugs as antidepression drugs instead of using them as a nanocarrier, which greatly expands the application of nanomaterials in depression treatment.

Insulin-incubated palladium clusters promote recovery after brain injury.

Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.

3D printed porous ß-Ca2SiO4 scaffolds derived from preceramic resin and their physicochemical and biological properties.

Silicate bioceramic scaffolds are of great interest in bone tissue engineering, but the fabrication of silicate bioceramic scaffolds with complex geometries is still challenging. In this study, three-dimensional (3D) porous ß-Ca2SiO4 scaffolds have been successfully fabricated from preceramic resin loaded with CaCO3 active filler by 3D printing. The fabricated ß-Ca2SiO4 scaffolds had uniform interconnected macropores (ca. 400 µm), high porosity (>78%), enhanced mechanical strength (ca. 5.2 MPa), and excellent apatite mineralization ability. Importantly, the results showed that the increase of sintering temperature significantly enhanced the compressive strength and the scaffolds sintered at higher sintering temperature stimulated the adhesion, proliferation, alkaline phosphatase activity, and osteogenic-related gene expression of rat bone mesenchymal stem cells. Therefore, the 3D printed ß-Ca2SiO4 scaffolds derived from preceramic resin and CaCO3 active fillers would be promising candidates for bone tissue engineering.

Bismuth-coated 80S15C bioactive glass scaffolds for photothermal antitumor therapy and bone regeneration.

Background: Malignant bone tumors usually occur in young people and have a high mortality and disability rate. Surgical excision commonly results in residual bone tumor cells and large bone defects, and conventional radiotherapy and chemotherapy may cause significant side effects. In this study, a bifunctional Bi-BG scaffold for near-infrared (NIR)-activated photothermal ablation of bone tumors and enhanced bone defect regeneration is fabricated. Methods: In this study, we prepared the Bi-BG scaffold by in-situ generation of NIR-absorbing Bi coating on the surface of a 3D-printing bioactive glass (BG) scaffold. SEM was used to analyze the morphological changes of the scaffolds. In addition, the temperature variation was imaged and recorded under 808 nm NIR laser irradiation in real time by an infrared thermal imaging system. Then, the proliferation of rat bone mesenchymal stem cells (rBMSCs) and Saos-2 on the scaffolds was examined by CCK-8 assay. ALP activity assay and RT-PCR were performed to test the osteogenic capacity. For in vivo experiments, the nude rat tumor-forming and rat calvarial defect models were established. At 8 weeks after surgery, micro-CT, and histological staining were performed on harvested calvarial samples. Results: The Bi-BG scaffolds have outstanding photothermal performance under the irradiation of 808 nm NIR at different power densities, while no photothermal effects are observed for pure BG scaffolds. The photothermal temperature of the Bi-BG scaffold can be effectively regulated in the range 26-100°C by controlling the NIR power density and irradiation duration. Bi-BG scaffolds not only significantly induces more than 95% of osteosarcoma cell death (Saos-2) in vitro, but also effectively inhibit the growth of bone tumors in vivo. Furthermore, they exhibit excellent capability in promoting osteogenic differentiation of rBMSCs and finally enhance new bone formation in the calvarial defects of rats. Conclusion: The Bi-BG scaffolds have bifunctional properties of photothermal antitumor therapy and bone regeneration, which offers an effective method to ablate malignant bone tumors based on photothermal effect.

3D printing of layered mesoporous bioactive glass/sodium alginate-sodium alginate scaffolds with controllable dual-drug release behaviors.

Scaffolds with controlled drug release are valuable for bone tissue engineering, but constructing the scaffolds with controllable dual-drug release behaviors is still a challenge. In this study, layered mesoporous bioactive glass/sodium alginate-sodium alginate (MBG/SA-SA) scaffolds with controllable dual-drug release behaviors were fabricated by 3D printing. The porosity and compressive strength of three-dimensional (3D) printed MBG/SA-SA scaffolds by cross-linking are about 78% and 4.2 MPa, respectively. As two model drugs, bovine serum albumin (BSA) and ibuprofen (IBU) were separately loaded in SA layer and MBG/SA layer, resulting in a relatively fast release of BSA and a sustained release of IBU. Furthermore, layered MBG/SA-SA scaffolds were able to stimulate human bone mesenchymal stem cells (hBMSCs) adhesion, proliferation and osteogenic differentiation than SA scaffolds. Hence, the 3D printed MBG/SA-SA scaffolds would be prospective for the treatment of bone defects.

3D printing of ceramic-based scaffolds for bone tissue engineering: an overview.

Currently, one of the most promising strategies in bone tissue engineering focuses on the development of biomimetic scaffolds. Ceramic-based scaffolds with favorable osteogenic ability and mechanical properties are promising candidates for bone repair. Three-dimensional (3D) printing is an additive manufacturing technique, which allows the fabrication of patient-specific scaffolds with high structural complexity and design flexibility, and gains growing attention. This review aims to highlight advances in 3D printing of ceramic-based scaffolds for bone tissue engineering. Technical limitations and practical challenges are emphasized and design considerations are also discussed.