Weizhen Chen

Regulation of the biological functions of osteoblasts and bone formation by Zn-incorporated coating on microrough titanium.

To improve the biological performance of titanium implant, a series of Zn-incorporated coatings were fabricated on the microrough titanium (Micro-Ti) via sol-gel method by spin-coating technique. The successful fabrication of the coating was verified by combined techniques of scanning electron microscopy, surface profiler, X-ray diffraction, X-ray photoelectron spectroscopy, and water contact angle measurements. The incorporated zinc existed as ZnO, which released Zn ions in a sustained manner. The Zn-incorporated samples (Ti-Zn0.08, Ti-Zn0.16, and Ti-Zn0.24) efficiently inhibited the adhesion of both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria. The in vitro evaluations including cell activity, alkaline phosphatase (ALP), mineralization, osteogenic genes expressions (Runx2, ALP, OPG, Col I, OPN, and OC), and tartrate-resistant acid phosphatase, confirmed that Ti-Zn0.16 sample was the optimal one to regulate the proliferation or differentiation for both osteoblasts and osteoclasts. More importantly, in vivo evaluations including Micro-CT analysis, push-out test, and histological observations verified that Ti-Zn0.16 implants could efficiently promote new bone formation after implantation for 4 and 12 weeks, respectively. The resulting material thus has potential application in orthopedic field.

Alendronate-loaded hydroxyapatite-TiO2 nanotubes for improved bone formation in osteoporotic rabbits

Early mechanical fixation between an implant and native bone is critically important for successful orthopedic implantation, especially for hosts suffering osteoporosis with reduced bone mass. To endow a titanium-based implant with a desirable local anti-osteoporosis property for enhancing its early osseointegration, alendronate-loaded hydroxyapatite-TiO2 nanotube (TNT-HA-Aln) substrates were fabricated and systematically characterized in this study. The results of Aln/Ca2+ release and Ca2+ concentration in an osteoclast medium verified that the release of Aln was significantly accelerated along with the acidity rise caused by osteoclast differentiation. Other in vitro tests, such as CCK-8, alkaline phosphatase (ALP), mineralization, gene expression (Runx2, Osterix, ALP, Col I, OPN, OC, OPG and RANKL), protein production (OPG and RANKL) and tartrate-resistant acid phosphatase (TRAP), proved that TNT-HA-Aln substrates have great potential for improving osteoblast proliferation/differentiation and inhibiting osteoclast differentiation. Moreover, in vivo tests, such as the push-out test, micro-CT and H&E staining proved that TNT-HA-Aln implants could efficiently improve local osseointegration after implantation for 3 months. The study provides an alternative to exploiting drug-device combinations to enhance early osseointegration in osteoporosis.

Influence of strontium ions incorporated into nanosheet-pore topographical titanium substrates on osteogenic differentiation of mesenchymal stem cells in vitro and on osseointegration in vivo

Biophysical cues or biochemical cues were proved to efficiently regulate the fate of mesenchymal stem cells (MSCs), but their synergistic effects on the biological functions of MSCs remain to be further investigated. In this study, titanium (Ti) substrates were fabricated with distinct sub-micrometer nanosheet-pore topography via a vapor alkaline treatment method. Strontium (Sr) ions were then incorporated into the Ti substrates via ion exchange. Apart from the influence of biophysical cues from topography, MSCs were simultaneously affected by the biochemical cues from the continuously released Sr ions. The MSCs grown onto Ti substrates with Sr incorporated in them displayed higher (p < 0.05 or p < 0.01) cellular functions than those of pure Ti substrates, including proliferation, the genes and proteins expressions of osteogenic markers and mineralization potential when comparing them with the results of those MSCs grown onto pure Ti substrates. Furthermore, the in vivo investigations demonstrated that the Sr incorporated Ti implants promoted new bone formation. All the results indicated that the incorporated Sr ions and the nanosheet-pore topography of the Ti substrates synergistically enhanced the osteogenic differentiation of MSCs in vitro and osseointegration in vivo. This study advances the understanding of the synergistic influence of biophysical cues and biochemical cues on MSC osteogenic differentiation.

Nanosheet-pore topographical titanium substrates: a biophysical regulator of the fate of mesenchymal stem cells

Recent reports have demonstrated that nano- or micro-scale topography could enhance the cellular functions of stem cells. In this study, a sub-micrometer topography composed of nanosheet-pore structures was fabricated on the pure titanium surface by a simple vapor alkaline-treatment method to understand more profoundly sub-micrometer topography mediated stem cell behaviors. The topography was characterized by scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, X-ray diffraction and contact angle measurements, respectively. It specifically mediated cellular functions of rat bone marrow-derived mesenchymal stem cells (MSCs) on cellular and molecular levels under either normal medium or osteoinductive medium conditions. The experimental results indicated that the topography dramatically promoted the adhesion of MSCs grown on the surface, but the shape, morphology and spreading of cells were not significantly affected. In addition, the study demonstrated that the formation of focal adhesion complexes (FAs) were highly dependent on the topography, which in turn affects the subsequent biological functions of MSCs, especially accelerating osteogenic differentiation of MSCs under different conditions. Overall, the sub-micrometer topographical titanium substrate was an excellent biophysical regulator of the fate of mesenchymal stem cells, specifically inducing their differentiation into osteoblasts.

Strontium folic acid derivative functionalized titanium surfaces for enhanced osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo

The introduction of the bioactive strontium (Sr) element has become an attractive method in the design of bio-functional layers on titanium surfaces. However, there are still no effective solutions to some of the associated problems including the toxicity of free Sr2+ ions and the rapid and irreversible loss of the strontium element from the bio-functional layers. In this study, we successfully fabricated a bioactive layer on Ti substrates with a strontium folic acid derivative (FASr). About 3.11 at% Sr was incorporated into the Ti surface. The characterization results showed that FASr was stable over a long period of time and minimal free Sr2+ ions were detected in simulated body fluid (SBF). In the in vitro experiment, the FASr could significantly promote the cell adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) over a short period. Furthermore, it could dramatically accelerate the bone formation around the implant. In vivo, a total of 30 7-week old male Sprague Dawley (SD) rats were applied for implantation tests. The results showed that this positive stimulatory effect became more evident in the later stages of the in vivo observation. This study provides an effective strategy for designing and optimizing Ti-based implants.

Phenylboronic acid-modified hollow silica nanoparticles for dual-responsive delivery of doxorubicin for targeted tumor therapy

Abstract This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for targeting tumor therapy. Doxorubicin (DOX) was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid (CytC–LA) via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers. The CytC–LA was used both as sealing agent and targeting motif. A series of characterizations demonstrated the successful construction of the drug delivery system. The system demonstrated pH and redox dual-responsive drug release behavior in vitro. The DOX loading HMSNs system displayed a good biocompatibility, which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis. In vivo data (tumor volume, tumor weight, terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining) proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect.

Deferoxamine loaded titania nanotubes substrates regulate osteogenic and angiogenic differentiation of MSCs via activation of HIF-1α signaling

To develop biomaterials for inducing osteogenic and angiogenic differentiation of mesenchymal stem cells (MSCs) is crucial for bone repair. In this study, we employed titania nanotubes (TNT) as drug nanoreservoirs to load deferoxamine (DFO), and then deposited chitosan (Chi) and gelatin (Gel) multilayer as coverage structure via layer-by-layer (LBL) assembly technique, resulting in TNT-DFO-LBL substrates. Scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements were employed to characterize the physical and chemical properties of the substrates. The results proved the successful fabrication of multilayer coating on TNT array. DFO released from the TNT arrays in a sustained manner. The drug-device combination titanium (Ti) substrates positively improved the adhesion, proliferation, osteogenic/angiogenic differentiation of MSCs and mediated the growth behavior of human umbilical vein endothelial cells (HUVECs). Moreover, the TNT-DFO-LBL substrates up-regulated osteogenic and angiogenic differentiation related genes expression of MSCs by activating HIF-1α signaling pathway. The approach presents here has a potential impact on the development of high quality Ti-based orthopedic implants.