3D printed porous titanium cages filled with simvastatin hydrogel promotes bone ingrowth and spinal fusion in rhesus macaques

Zhang, Wen; Sun, Chuiguo; Zhu, Junxiong; Zhang, Weifang; Leng, Huijie; Song, Chunli

doi:10.1039/d0bm00361a

Cited by 30 publications

(26 citation statements)

References 30 publications

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“…The VPA hydrogel was synthesized as described [ 20 ]. Briefly, 200 μl of poloxamer 407 hydrogel (BASF, Ludwigshafen, Germany) (1/4 volume ratio) was mixed with 50 μg of valproic acid and 0.01 M phosphate-buffered saline (PBS) (pH 7.4, at 4 °C).…”

Section: Methodsmentioning

confidence: 99%

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Tao

et al. 2021

J Mater Sci: Mater Med

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The purpose was to observe whether valproic acid (VPA) has a positive effect on bone-defect repair via activating the Notch signaling pathway in an OVX rat model. The MC3T3-E1 cells were cocultured with VPA and induced to osteogenesis, and the osteogenic activity was observed by alkaline phosphatase (ALP) staining, Alizarin Red (RES) staining and Western blotting (WB). Then the hydrogel-containing VPA was implanted into the femoral epiphysis bone-defect model of ovariectomized (OVX) rats for 12 weeks. Micro-CT, biomechanical testing, histology, immunofluorescence, RT-qPCR, and WB analysis were used to observe the therapeutic effect and explore the possible mechanism. ALP and ARS staining and WB results show that the cell mineralization, osteogenic activity, and protein expression of ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, and JAG1 of VPA group is significantly higher than the control group. Micro-CT, biomechanical testing, histology, immunofluorescence, and RT-qPCR evaluation show that group VPA presented the stronger effect on bone strength, bone regeneration, bone mineralization, higher expression of VEGFA, BMP-2, ALP, OPN, RUNX-2, OC, Notch 1, HES1, HEY1, and JAG1 of VPA when compared with OVX group. Our current study demonstrated that local treatment with VPA could stimulate repair of femoral condyle defects, and these effects may be achieved by activating Notch signaling pathway and acceleration of blood vessel and bone formation.

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Section: Methodsmentioning

confidence: 99%

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Tao

et al. 2021

J Mater Sci: Mater Med

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“…Our large animal study showed that 0.5 and 1 mg injections of simvastatin in minipig vertebrae were effective to enhance implant fixation and improve bone quality 8,9 . Our previous data showed that 3D‐printed porous cages with 0.5 mg simvastatin in hydrogel can promote bone ingrowth and spinal fusion in adult male rhesus macaques 10 . The possible overdose in this study may also explain the phenomenon that we did not find any difference between the SIM‐C 0.5 mg and SIM‐BPC 0.5 mg group in the osteoporosis model.…”

Section: Discussionmentioning

confidence: 74%

“…Local delivery of simvastatin is another option that can be used. Our previous studies have shown that locally applied statins with sustained release can improve the quality of osteoporotic bone, promote defect healing, or enhance pedicle‐screw fixation in animals, from rats 6 and rabbits, 7 to minipigs 8,9 and rhesus macaques 10 …”

Section: Introductionmentioning

confidence: 99%

Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals

Zhu

Zhang

Jia

et al. 2020

Annals of the New York Academy of Sciences

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Simvastatin is a translational drug that may be used to induce local bone formation. In this study, simvastatin microcrystals were made by a wet media milling method, and then we verified the osteogenic effect of the microcrystals in rat ovariectomy (OVX)–induced osteoporosis and femur defect models. For the osteoporosis model, we delivered simvastatin microcrystals to the tibia with poloxamer hydrogels via an intraosseous injection. Bone mineral density and the ultimate force of the treated tibia were significantly improved after injection of simvastatin microcrystals at 0.5 and 1 mg compared with the OVX or 0‐mg control groups. For the femur defect model, simvastatin microcrystals were incorporated in clinically used calcium phosphate cements (CPCs) as an implant. Quantitative analysis of bone regeneration by microcomputed tomography (μCT) showed improved bone morphology with simvastatin microcrystals at 50 and 100 μg, compared with the CPC vehicle. A semiquantitative scale for histology assessment further demonstrated a higher bone regeneration score in the drug‐loaded groups. Our study shows that simvastatin microcrystals can promote bone formation by local delivery using a poloxamer hydrogel or CPC, which may be translationally useful.

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“…When hydrogel is used as a drug carrier, it disseminates drug molecules into surrounding tissues or cells through interconnected pores ( Chyzy and Plonska-Brzezinska, 2020 ). For instance, Zhang W et al (2020) developed a poloxamer 407 hydrogel loaded with simvastatin for filling porous 3D-printed titanium alloy intervertebral cages that achieved stable drug release and significantly promoted bone growth. Furthermore, the strategy of promoting bone regeneration through stem cell transplantation has become an important research topic to repair bone defects and promote bone integration.…”

Section: Surface Modification Technologymentioning

confidence: 99%

Advanced Surface Modification for 3D-Printed Titanium Alloy Implant Interface Functionalization

Sheng

Wang

et al. 2022

Front. Bioeng. Biotechnol.

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With the development of three-dimensional (3D) printed technology, 3D printed alloy implants, especially titanium alloy, play a critical role in biomedical fields such as orthopedics and dentistry. However, untreated titanium alloy implants always possess a bioinert surface that prevents the interface osseointegration, which is necessary to perform surface modification to enhance its biological functions. In this article, we discuss the principles and processes of chemical, physical, and biological surface modification technologies on 3D printed titanium alloy implants in detail. Furthermore, the challenges on antibacterial, osteogenesis, and mechanical properties of 3D-printed titanium alloy implants by surface modification are summarized. Future research studies, including the combination of multiple modification technologies or the coordination of the structure and composition of the composite coating are also present. This review provides leading-edge functionalization strategies of the 3D printed titanium alloy implants.

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3D printed porous titanium cages filled with simvastatin hydrogel promotes bone ingrowth and spinal fusion in rhesus macaques

Abstract: Sustainable release of simvastatin from poloxamer 407 hydrogel in 3D-printed porous Ti6Al4V for spinal fusion in rhesus macaques.

Cited by 30 publications

References 30 publications

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals

Advanced Surface Modification for 3D-Printed Titanium Alloy Implant Interface Functionalization

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