Loading rutin on surfaces by the layer-by-layer assembly technique to improve the oxidation resistance and osteogenesis of titanium implants in osteoporotic rats.

The purpose of this study was to construct a rutin-controlled release system on the surface of Ti substrates and investigate its effects on osteogenesis and osseointegration on the surface of implants. The base layer, polyethylenimine (PEI), was immobilised on a titanium substrate. Then, hyaluronic acid (HA)/chitosan (CS)-rutin (RT) multilayer films were assembled on the PEI using layer-by-layer (LBL) assembly technology. We used scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and contact angle measurements to examine all Ti samples. The drug release test of rutin was also carried out to detect the slow-release performance. The osteogenic abilities of the samples were evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The results (SEM, FTIR and contact angle measurements) all confirmed that the PEI substrate layer and HA/CS-RT multilayer film were effectively immobilised on titanium. The drug release test revealed that a rutin controlled release mechanism had been successfully established. Furthermore, thein vitrodata revealed that osteoblasts on the coated titanium matrix had greater adhesion, proliferation, and differentiation capacity than the osteoblasts on the pure titanium surface. When MC3T3-E1 cells were exposed to H2O2-induced oxidative stressin vitro, cell-based tests revealed great tolerance and increased osteogenic potential on HA/CS-RT substrates. We also found that the HA/CS-RT coating significantly increased the new bone mass around the implant. The LBL-deposited HA/CS-RT multilayer coating on the titanium base surface established an excellent rutin-controlled release system, which significantly improved osseointegration and promoted osteogenesis under oxidative stress conditions, suggesting a new implant therapy strategy for patients with osteoporosis.

Coating Polyelectrolyte Multilayers Loaded with Quercetin on Titanium Surfaces by Layer-By-Layer Assembly Technique to Improve Surface Osteogenesis Under Osteoporotic Condition.

Titanium (Ti) and its alloy implants are widely used in the field of orthopedics, and osteoporosis is an important reason for implantation failure. This study aimed to establish a quercetin (QTN) controlled release system on the surface of titanium implants and to study its effects on osteogenesis and osseointegration on the surface of implants. Polyethylenimine (PEI) was first immobilized on a titanium substrate as the base layer, and then, hyaluronic acid/chitosan-quercetin (HA/CS-QTN) multilayer films were assembled on the PEI layer by a self-assembly technique. Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and contact angle measurements were used to characterize and analyze the samples. The release characteristics of QTN were studied by release assays. The osteogenic ability of the samples was evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The FTIR, SEM, and contact angle measurements all showed that the PEI substrate layer and HA/CS-QTN multilayer film were successfully immobilized on the titanium matrix. The drug release test showed the successful establishment of a QTN controlled release system. The in vitro results showed that osteoblasts exhibited higher adhesion, proliferation and differentiation ability on the coated titanium matrix than on the pure titanium surface. In addition, the in vivo results showed that the HA/CS-QTN coating significantly increased the new bone mass around the implant. By depositing a PEI matrix layer and HA/CS-QTN multilayer films on titanium implants, a controlled release system of QTN was established, which improved implant surface osseointegration under osteoporotic conditions. This study proposes a new implant therapy strategy for patients with osteoporosis.

Surface Functionalization with Proanthocyanidins Provides an Anti-Oxidant Defense Mechanism That Improves the Long-Term Stability and Osteogenesis of Titanium Implants.

PURPOSE: Aseptic loosening is a major complication after total joint replacement. Reactive oxygen species generated by local tissue cells and liberated from implant surfaces have been suggested to cause implant failures. Surface modification of titanium (Ti)-based implants with proanthocyanidins (PAC) is a promising approach for the development of anti-oxidant defense mechanism to supplement the mechanical functions of Ti implants. In this study, a controlled PAC release system was fabricated on the surface of Ti substrates using the layer-by-layer (LBL) assembly. MATERIALS AND METHODS: Polyethyleneimine (PEI) base layer was fabricated to enable layer-by-layer (LBL) deposition of hyaluronic acid/chitosan (HA/CS) multi-layers without or with the PAC. Surface topography and wettability of the fabricated HA/CS-PAC substrates were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR) and contact angle measurement. PAC release profiles were investigated using drug release assays. MC3T3-E1 pre-osteoblast cells were used to assess the osteo-inductive effects of HA/CS-PAC substrates under conditions H2O2-induced oxidative stress in vitro. A rat model of femoral intramedullary implantation evaluated the osseo-integration and osteo-inductive potential of the HA/CS-PAC coated Ti implants in vivo. RESULTS: SEM, AFM, FTIR and contact angle measurements verified the successful fabrication of Ti surfaces with multi-layered HA/CS-PAC coating. Drug release assays revealed controlled and sustained release of PAC over 14 days. In vitro, cell-based assays showed high tolerability and enhanced the osteogenic potential of MC3T3-E1 cells on HA/CS-PAC substrates when under conditions of H2O2-induced oxidative stress. In vivo evaluation of femoral bone 14 days after femoral intramedullary implantation confirmed the enhanced osteo-inductive potential of the HA/CS-PAC coated Ti implants. CONCLUSION: Multi-layering of HA/CS-PAC coating onto Ti-based surfaces by the LBL deposition significantly enhances implant osseo-integration and promotes osteogenesis under conditions of oxidative stress. This study provides new insights for future applications in the field of joint arthroplasty.

The fast degradation of ß-TCP ceramics facilitates healing of bone defects by the combination of BMP-2 and Teriparatide.

Accumulating evidence suggests that the degradation and resorption of calcium phosphate ceramics is always relatively slow, which may inhibit calcium phosphate ceramics' replacement by new bone tissues and the ultimate bone defect repair. Bone morphogenetic proteins (BMPs) and Teriparatide (PTH) are extensively applied in the treatment of bone pathologies, while their effects on the degradation of calcium phosphate ceramics is limited. In this study, we tested the effects of BMP and PTH on degradation of ß-tricalcium phosphate (ß-TCP) ceramics and bone formation on ß-TCP in ovariectomized (OVX) rat models. After establishment of femur defect model on OVX rats, the BMP + PTH group's rats were injected Teriparatide (30 µg/kg) subcutaneous every other day, while rats of control group and group BMP were injected equal-to-group volume sterilized saline water. Twelve weeks after femur surgery, all rats were sacrificed for Micro-CT scanning and histology tests. The results showed that BMP facilitated degradation of ß-TCP and new bone formation on ß-TCP ceramics. And PTH showed an additional effect on degradation of ß-TCP when combined with BMP. In addition, the results explained that PTH promoted the remodeling of the bone callus occurred during repair.