Recent Advances on Cerium Oxide-Based Biomaterials: Toward the Next Generation of Intelligent Theranostics Platforms.

Disease or organ damage due to unhealthy living habits, or accidents, is inevitable. Discovering an efficient strategy to address these problems is urgently needed in the clinic. In recent years, the biological applications of nanotechnology have received extensive attention. Among them, as a widely used rare earth oxide, cerium oxide (CeO2 ) has shown good application prospects in biomedical fields due to its attractive physical and chemical properties. Here, the enzyme-like mechanism of CeO2 is elucidated, and the latest research progress in the biomedical field is reviewed. At the nanoscale, Ce ions in CeO2 can be reversibly converted between +3 and +4. The conversion process is accompanied by the generation and elimination of oxygen vacancies, which give CeO2 the performance of dual redox properties. This property facilitates nano-CeO2 to catalyze the scavenging of excess free radicals in organisms, hence providing a possibility for the treatment of oxidative stress diseases such as diabetic foot, arthritis, degenerative neurological diseases, and cancer. In addition, relying on its excellent catalytic properties, customizable life-signaling factor detectors based on electrochemical techniques are developed. At the end of this review, an outlook on the opportunities and challenges of CeO2 in various fields is provided.

A Unified Therapeutic-Prophylactic Tissue-Engineering Scaffold Demonstrated to Prevent Tumor Recurrence and Overcoming Infection toward Bone Remodeling.

Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and it is difficult for them to self-repair large bone defects. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS2 improves the hydrogel system, which has excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on the Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradually released Gd3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, this strategy supplies a method to prepare multifunctional bone-defect-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for bone tissue engineering.

Spatial Distribution of Biomaterial Microenvironment pH and Its Modulatory Effect on Osteoclasts at the Early Stage of Bone Defect Regeneration.

It is generally accepted that biodegradable materials greatly influence the nearby microenvironment where cells reside; however, the range of interfacial properties has seldom been discussed due to technical bottlenecks. This study aims to depict biomaterial microenvironment boundaries by correlating interfacial H+ distribution with surrounding cell behaviors. Using a disuse-related osteoporotic mouse model, we confirmed that the abnormal activated osteoclasts could be suppressed under relatively alkaline conditions. The differentiation and apatite-resorption capability of osteoclasts were "switched off" when cultured in titrated material extracts with pH values higher than 7.8. To generate a localized alkaline microenvironment, a series of borosilicates were fabricated and their interfacial H+ distributions were monitored spatiotemporally by employing noninvasive microtest technology. By correlating interfacial H+ distribution with osteoclast "switch on/off" behavior, the microenvironment boundary of the tested material was found to be 400 ± 50 µm, which is broader than the generally accepted value, 300 µm. Furthermore, osteoporotic mice implanted with materials with higher interfacial pH values and boarder effective ranges had lower osteoclast activities and a thicker new bone. To conclude, effective proton microenvironment boundaries of degradable biomaterials were depicted and a weak alkaline microenvironment was shown to promote regeneration of osteoporotic bones possibly by suppressing abnormal activated osteoclasts.

Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence.

Polyethylenimine (PEI) functionalized carbon dots (CD-PEI) were fabricated by one-step microwave assisted pyrolysis of glycerol and branched PEI25k mixture where the formation of carbon nanoparticles and the surface passivation were accomplished simultaneously. In this hybrid C-dot, PEI molecule played two key roles in the system - as a nitrogen-rich compound to passivate surface to enhance the fluorescence and as a polyelectrolyte to condense DNA. This CD-PEI was shown to be water soluble and emit stable bright multicolor fluorescence relying on excitation wavelength. The DNA condensation capability and cytotoxicity of CD-PEI could be regulated by pyrolysis time possibly due to the somewhat destruction of PEI during the formation of carbon dots. CD-PEI obtained at an appropriate pyrolysis time exhibited lower toxicity, higher or comparable gene expression of plasmid DNA in COS-7 cells and HepG2 cells relative to control PEI25k. Intriguingly, the CD-PEIs internalized into cells displayed tunable fluorescent emission under varying excitation wavelength, suggesting the potential application of CD-PEI in gene delivery and bioimaging.