Novel pH-Responsive CaO2@ZIF-67-HA-ADH Coating That Efficiently Enhances the Antimicrobial, Osteogenic, and Angiogenic Properties of Titanium Implants.

Titanium-based implants often lead to premature implant failure due to the lack of antimicrobial, osteogenic, and angiogenic properties. To this end, a new strategy was developed to fabricate CaO2@ZIF-67-HA-ADH coating on titanium surfaces by combining calcium peroxide (CaO2) nanoparticles, zeolite imidazolate framework-67 (ZIF-67), and the chemical coupling hyaluronic acid-adipic acid dihydrazide (HA-ADH). We characterized CaO2@ZIF-67-HA-ADH with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-atomic emission spectrometry (ICP-AES). The results demonstrated that CaO2@ZIF-67-HA-ADH was pH-sensitive and decomposed rapidly under acidic conditions, and it released inclusions slowly under neutral conditions. Antibacterial experiments showed that the CaO2@ZIF-67-HA-ADH coating had excellent antibacterial properties and effectively killed methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1). Cell experiments revealed that the CaO2@ZIF-67-HA-ADH coating promoted pro-osteoblast adhesion, proliferation, and differentiation and also promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs), exhibiting excellent osteogenic and angiogenic properties. In in vivo animal implantation experiments, the CaO2@ZIF-67-HA-ADH coating exhibited strong antimicrobial activity early after implantation and excellent osseointegration later after implantation. In conclusion, the pH-responsive CaO2@ZIF-67-HA-ADH coating conferred excellent antibacterial, osteogenic, and angiogenic properties to titanium implants, which effectively enhanced osseointegration of the implants and prevented bacterial infection; the coating shows promise for use in the treatment of bone defects.

Doped Multiple Nanoparticles with Hydroxyapatite Coating Show Diverse Health Effects in vivo.

Introduction: The lack of osteoinductive, angiogenic and antimicrobial properties of hydroxyapatite coatings (HA) on titanium surfaces severely limits their use in orthopedic and dental implants. Therefore, we doped SiO2, Gd2O3 and CeO2 nanoparticles into HA to fabricate a HASiGdCe coating with a combination of decent antibacterial, angiogenic and osteogenic properties by the plasma spraying technique. Methods: The HASiGdCe coating was analyzed by SEM (EDS), surface roughness tests, contact angle tests, XRD, FTIR spectroscopy, tensile tests and electrochemical dynamic polarization tests. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO-1) were used as representative bacteria to verify the antibacterial properties of the HASiGdCe coating. We evaluated the cytocompatibility and in vitro osteoinductivity of the HASiGdCe coating by investigating its effect on the cell viability and osteogenic differentiation of MC3T3-E1 cells. We assessed the in vitro angiogenic activity of the HASiGdCe coating by migration assay, tube formation assay, and RT‒PCR analysis of angiogenic genes in HUVECs. Finally, we used infected animal femur models to investigate the biosafety, antimicrobial and osteointegration properties of the HASiGdCe coating in vivo. Results: Through various characterization experiments, we demonstrated that the HASiGdCe coating has suitable microscopic morphology, physical phase characteristics, bonding strength and bioactivity to meet the coating criteria for orthopedic implants. The HASiGdCe coating can release Gd3+ and Ce4+, showing strong antibacterial properties against MRSA and PAO-1. The HASiGdCe coating has been shown to have superior osteogenic and angiogenic properties compared to the HA coating in in vitro cellular experiments. Animal implantation experiments have shown that the HASiGdCe coating also has excellent biosafety, antimicrobial and osteogenic properties in vivo. Conclusion: The HASiGdCe coating confers excellent antibacterial, angiogenic and osteogenic properties on titanium implants, which can effectively enhance implant osseointegration and prevent bacterial infections, and it accordingly has promising applications in the treatment of bone defects related to orthopedic and dental sciences.

Functional hydrogels for the repair and regeneration of tissue defects.

Tissue defects can be accompanied by functional impairments that affect the health and quality of life of patients. Hydrogels are three-dimensional (3D) hydrophilic polymer networks that can be used as bionic functional tissues to fill or repair damaged tissue as a promising therapeutic strategy in the field of tissue engineering and regenerative medicine. This paper summarises and discusses four outstanding advantages of hydrogels and their applications and advances in the repair and regeneration of tissue defects. First, hydrogels have physicochemical properties similar to the extracellular matrix of natural tissues, providing a good microenvironment for cell proliferation, migration and differentiation. Second, hydrogels have excellent shape adaptation and tissue adhesion properties, allowing them to be applied to a wide range of irregularly shaped tissue defects and to adhere well to the defect for sustained and efficient repair function. Third, the hydrogel is an intelligent delivery system capable of releasing therapeutic agents on demand. Hydrogels are capable of delivering therapeutic reagents and releasing therapeutic substances with temporal and spatial precision depending on the site and state of the defect. Fourth, hydrogels are self-healing and can maintain their integrity when damaged. We then describe the application and research progress of functional hydrogels in the repair and regeneration of defects in bone, cartilage, skin, muscle and nerve tissues. Finally, we discuss the challenges faced by hydrogels in the field of tissue regeneration and provide an outlook on their future trends.

Hydrogel systems for targeted cancer therapy.

When hydrogel materials with excellent biocompatibility and biodegradability are used as excellent new drug carriers in the treatment of cancer, they confer the following three advantages. First, hydrogel materials can be used as a precise and controlled drug release systems, which can continuously and sequentially release chemotherapeutic drugs, radionuclides, immunosuppressants, hyperthermia agents, phototherapy agents and other substances and are widely used in the treatment of cancer through radiotherapy, chemotherapy, immunotherapy, hyperthermia, photodynamic therapy and photothermal therapy. Second, hydrogel materials have multiple sizes and multiple delivery routes, which can be targeted to different locations and types of cancer. This greatly improves the targeting of drugs, thereby reducing the dose of drugs and improving treatment effectiveness. Finally, hydrogel can intelligently respond to environmental changes according to internal and external environmental stimuli so that anti-cancer active substances can be remotely controlled and released on demand. Combining the abovementioned advantages, hydrogel materials have transformed into a hit in the field of cancer treatment, bringing hope to further increase the survival rate and quality of life of patients with cancer.

VEGF mitigates bisphosphonate-induced apoptosis and differentiation inhibition of MC3T3-E1 cells.

The present study aimed to investigate whether VEGF was involved in bisphosphonate (BP)-induced apoptosis and differentiation of osteoblasts. Murine MC3T3-E1 osteoblasts were stimulated with zoledronic acid (ZA) for 7 days. VEGF mRNA and protein expression levels were determined via reverse transcription-quantitative PCR and western blot analysis, respectively. Cell viability was evaluated using Cell Counting Kit-8 assay. In addition, the cell apoptotic rate and the expression levels of apoptosis-related proteins were measured using a TUNEL staining kit and western blot analysis, respectively. To evaluate mineralization, cells were stained with alizarin red, while the secretion levels of alkaline phosphatase (ALP) were measured using the corresponding assay kit. Finally, the expression levels of differentiation-related proteins and proteins of the Nod-like receptor family pyrin domain-containing 3 (NLRP3)/caspase 1/gasdermin D (GSDMD) pyroptosis pathway were measured by western blot analysis. VEGF expression level was notably decreased in ZA-stimulated MC3T3-E1 cells. However, the viability of these cells was enhanced following VEGF addition. Furthermore, VEGF attenuated apoptosis, promoted mineralization and increased ALP activity in ZA-stimulated MC3T3-E1 cells. The ZA-mediated decrease in the protein expression of the osteogenic genes osteopontin, osteocalcin and runt-related transcription factor 2 was restored after MC3T3-E1 cell treatment with 10 ng/ml VEGF. The present study demonstrated that VEGF could attenuate BP-induced apoptosis and differentiation of MC3T3 cells by regulating the NLRP3/caspase 1/GSDMD pathway.

Fabrication of substituted hydroxyapatite-starch-clay bio-composite coated titanium implant for new bone formation.

The clay/polymeric matrices have much attention from researchers in bio-medical applications due to their numerous uses. This study introduces new orthopedic titanium (Ti) implant with increasing bio-activity by treating the surface of the Ti implant with bio-compatible composite coating. Wollastonite (WST) clay combined minerals (Mg2+and Gd3+) substituted hydroxyapatite (HAP)/Starch composite was prepared using in-situ co-precipitation method. It was successfully coated on the orthopedic grade Ti plate by the Electrophoretic Deposition (EPD) method. The functionality, phase, morphology, and bio-activity analysis of the composite were evaluated by FT-IR, XRD, HR-TEM, and SEM analysis, respectively. The mechanical property, i.e., Vickers microhardness value of the MHAP/Starch/WST composite coated Ti plate, showed 242 ± 1.92 Hv. The in-vitro MG-63 osteoblast cells viability, differentiation, and Ca mineralization of MHAP/Starch/WST composite suggests that this new implant will be used for bone regeneration application after careful evaluation of in-vivo and clinical studies.

Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells.

Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.