3D-printed Strontium-Titanium Scaffolds Incorporated with Highly Bioactive Serum Exosomes Promotes Critical Bone Defect Repair by Enhancing Osteogenesis and Angiogenesis

AUTHORS

Hao Liu, Ranli Gu, Wei Li, Lijun Zeng, Yuan Zhu, Siyi Wang, Xuenan Liu, Boon Chin Heng, Yunsong Liu, Yongsheng Zhou

ABSTRACT

Background

Large bone defect healing faces significant challenges because of inadequate bone regeneration and revascularization. Serum exosomes (sEXO) during bone defect repair are rich in osteogenic factors. Titanium (Ti) scaffolds and low dose strontium (Sr) can promote bone regeneration. Here, a “cell-free scaffold engineering” strategy that incorporates strontium and highly bioactive sEXO within a 3D-printed Ti scaffold is developed.

Methods

Sr-Ti-sEXO composite was prepared by ion implantation and ultra-high-speed centrifugation. Alkaline phosphatase (ALP), Alizarin red (ARS), immunofluorescence (IF) staining, and polymerase chain reaction (PCR) were used to detect the osteogenic effect of Sr-Ti-sExo on bone marrow mesenchymal stem cells (BMSCs). Tartrate-resistant acid phosphatase (TRAP) staining, and PCR were used to detect the osteoclast effect of Sr-Ti-sEXO on RAW264.7. The vascularization effect of Sr-Ti-sEXO on human umbilical vein endothelial cells (HUVECs) was investigated by scratch and migration experiments. Micro-CT and histological staining were used to study the osteogenic and vasculogenic effects of Sr-Ti-sEXO implanted in rabbit large radius defect at 6 and 12 weeks in vivo. RNA-seq was used to explore the potential mechanism.

Results

Sr-Ti-sEXO composite promoted early osteogenesis and inhibited osteoclast formation through the combined release of Sr ions and sEXO, and sustained release of Sr ions enhanced bone conduction, bone induction and inhibited fibroblasts. sEXO can promote the vascular reconstruction of CBD in fracture stage, which has the dual effect of promoting bone and promoting angiogenesis in critical bone defect repair. These effects are regulated by multiple miRNAs that shuttle in sEXO.

Conclusions

Sr-Ti-sEXO has favourable sustained release performance, osteogenic and vasogenic effects, which is a biocompatible and clinically feasible critical bone defect repair strategy. This study also broadens the biomedical potential of exosomes with specific functions such as sEXO in fracture stage. Based on the relative abundance of sEXO, a sEXO library for clinical treatment can be established.

Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

AUTHORS

Ying Yang, Min Li, Bixia Zhou, Xulei Jiang, Dou Zhang, Hang Luo

ABSTRACT

Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.

TiO2 Nanocoatings with Controllable Crystal Type and Nanoscale Topography on Zirconia Implants to Accelerate Bone Formation

AUTHORS

Nan Li, Zhichao Liu, Guanqi Liu, Zhi Wang, Xianwei Guo, Chuanbin Guo, Jianmin Han

ABSTRACT

In dentistry, zirconia implants have emerged as a promising alternative for replacing missing teeth due to their superior aesthetic performance and chemical stability. To improve the osseointegration of zirconia implants, modifying their surface with hierarchical micro/nanotopography and bioactive chemical composition are two effective ways. In this work, a microscale topography was prepared on a zirconia surface using hydrofluoric acid etching, and then a 50 nm TiO2 nanocoating was deposited via atomic layer deposition (ALD). Subsequently, an annealing treatment was used to transform the TiO2 from amorphous to anatase and simultaneously generate nanoscale topography. Various investigations into the coating surface morphology, topography, wettability, and chemical composition were carried out using scanning electron microscopy, white light interferometry, contact-angle measurement, X-ray diffraction, and X-ray photoelectron spectroscopy. In addition, in vitro cytocompatibility and osteogenic potential performance of the coatings were evaluated by human bone marrow mesenchymal stem cells (hBMSCs), and in vivo osseointegration performance was assessed in a rat femoral condyle model. Moreover, the possible mechanism was also investigated. The deposition of TiO2 film with/without annealing treatment did not alter the microscale roughness of the zirconia surface, whereas the nanotopography changed significantly after annealing. The in vitro studies revealed that the anatase TiO2 coating with regular wavelike nanostructure could promote the adhesion and proliferation of osteoblasts and further improve the osteogenic potential in vitro and osseointegration in vivo. These positive effects may be caused by nanoscale topography via the canonical Wnt/β-catenin pathway. The results suggest that using ALD in combination with annealing treatment to fabricate a nanotopographic TiO2 coating is a promising way to improve the osteogenic properties of zirconia implants.

3D gel-printed porous magnesium scaffold coated with dibasic calcium phosphate dihydrate for bone repair in vivo

AUTHORS

Yuxuan Zhang, Tao Lin, Haoye Meng, Xueting Wang, Hong Peng, Guangbo Liu, Shuai Wei, Qiang Lu, Yu Wang, Aiyuan Wang, Wenjing Xu, Huiping Shao, Jiang Peng

ABSTRACT

Background

Objective: The treatment of bone defect has always been a difficult problem in orthopedic clinic. The search for alternative biodegradable implants is a hot topic. The development of biodegradable magnesium scaffolds for the treatment of bone defects has long been a goal of the public.

Methods

In this study, we proposed a porous magnesium scaffold prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material. The porous magnesium granular scaffold was prepared by 3D gel printing technology and modified by DCPD (Dibasic Calcium Phosphate Dihydrate) coating. The biocompatibility, degradation rate, and osteogenic ability of the scaffold were evaluated in vitro and in vivo.

Results

The biocompatibility, in vivo degradation and bone defect healing response of the implants were investigated. Porous magnesium scaffolds were successfully prepared, and the strength of sintered scaffolds reached 5.38 ​MPa. The degradation rates of scaffolds were significantly reduced after coating with DCPD. The cell compatibility evaluation showed that DCPD-coated Mg scaffold was suitable for cell proliferation. In vivo biosafety monitoring showed that scaffold implantation did not cause an increase in Mg ion concentration in vivo, and no toxic damage was detected in the liver or kidney. Micro-CT and pathological results showed that a large amount of new bone was formed at 6 weeks. At 12 weeks, approximately 52% of the scaffold volume remained. At 24 weeks, osteogenesis, which was stimulated by some residual scaffold, still can be observed. In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.

Conclusion

In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.

The Translational potential of this article

The translational potential of this article is to make use of the advantages of 3D gel printing technology with higher efficiency and lower cost compared with SLM and SLS technologies, and use pure magnesium powder as raw material to prepare degradable porous magnesium metal scaffolds, opening up a new technical route for the preparation of degradable porous magnesium scaffolds which are made for bone defect regeneration in the future.

Decaffeinated green tea extract as a nature-derived antibiotic alternative: An application in antibacterial nano-thin coating on medical implants

AUTHORS

Jihyo Park, Lianhua Chi, Hee-Young Kwon, Jisoo Lee, Seunghwi Kim, Seonki Hong

ABSTRACT

Plant-derived polyphenols have emerged as molecular building blocks for biomedical architectures. However, the isolation of polyphenols from other components requires labor-intensive procedures, which increases costs and often raises environmental concerns. Here, we suggest that decaffeination can be a convenient and cost-effective method for enhancing the antibacterial performance of polyphenol-rich tea extracts. As a demonstration, we compared the properties of a nano-thin coating made of decaffeinated (dGT coating) and raw green tea extract (GT coating). The dGT coating exhibited enhanced antibacterial performance with regard to bacterial killing and prevention of bacterial attachment compared with the GT coating. Moreover, the chemical reactivity of the dGT coating was further utilized for secondary modifications, which enhanced the overall antibacterial performance of the modified surface. Given its intrinsic low toxicity, we envision that the developed antibacterial coating is ready for the next steps toward application in real clinical settings.

Preliminary study on the osseointegration effects of contactless automated implant cavity preparation via femtosecond laser ablation

AUTHORS

Shanshan Liang, Jianqiao Zheng, and Fusong Yuan

ABSTRACT

Microrobots were used to control the femtosecond laser ablation of bone tissues to prepare implant cavities for dental implant surgery. The method was optimized through depth-of-cut experiments of ex vivo rabbit femurs, and the optimized method was used to prepare implant cavities on the left femurs of eight live rabbits. A power of 10 W and a scanning rate of 4000 mm/s were found to be optimal. After seven days of osteoinduction, the expression of collagen type I was significantly higher in the experimental group than in the control group (manually drilled implant cavities). The bone–implant contacts of the experimental group at 4 and 8 weeks were 9.65% and 23.08%, respectively.