Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

Ma, Xiao; Gao, Yun; Zhao, Duoyi; Zhang, Weilin; Zhao, Wei; Wu, Meng; Cui, Yan; Li, Qin; Zhang, Zhe; Ma, Chengbin

doi:10.3390/nano12010047

Cited by 20 publications

(12 citation statements)

References 127 publications

(171 reference statements)

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“…Therefore, patients are not required to rely on continuous and repeated oral intake of medication, which will improve patient compliance [ 7 ]. A wide variety of implantable drug delivery systems have been described, including subcutaneous implants [ 10 , 11 , 12 , 13 , 14 ], cardiovascular devices [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ], or orthopaedic implants [ 22 , 23 ]. Among these type of implantable devices, intranasal implants have been described for local drug delivery [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

et al. 2023

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The use of intranasal implantable drug delivery systems has many potential advantages for the treatment of different diseases, as they can provide sustained drug delivery, improving patient compliance. We describe a novel proof-of-concept methodological study using intranasal implants with radiolabeled risperidone (RISP) as a model molecule. This novel approach could provide very valuable data for the design and optimization of intranasal implants for sustained drug delivery. RISP was radiolabeled with 125I by solid supported direct halogen electrophilic substitution and added to a poly(lactide-co-glycolide) (PLGA; 75/25 D,L-Lactide/glycolide ratio) solution that was casted on top of 3D-printed silicone molds adapted for intranasal administration to laboratory animals. Implants were intranasally administered to rats, and radiolabeled RISP release followed for 4 weeks by in vivo non-invasive quantitative microSPECT/CT imaging. Percentage release data were compared with in vitro ones using radiolabeled implants containing either 125I-RISP or [125I]INa and also by HPLC measurement of drug release. Implants remained in the nasal cavity for up to a month and were slowly and steadily dissolved. All methods showed a fast release of the lipophilic drug in the first days with a steadier increase to reach a plateau after approximately 5 days. The release of [125I]I− took place at a much slower rate. We herein demonstrate the feasibility of this experimental approach to obtain high-resolution, non-invasive quantitative images of the release of the radiolabeled drug, providing valuable information for improved pharmaceutical development of intranasal implants.

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Section: Introductionmentioning

confidence: 99%

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

et al. 2023

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“…Systemic use of antibiotics can easily lead to low concentrations of antibiotics around the implant, making it difficult to effectively fight against bacteria; in addition, high concentrations of systemic antibiotics can also cause damage to other tissues in the body. However, the topical delivery system of titanium implants allows higher concentrations of antibiotics to penetrate the biofilm and bone tissue, solving the above problems to some extent [12,13]. Compared with systemic drug delivery systems, the advantages of topical drug delivery systems on titanium implants are that they can provide better drug concentrations in the bone microenvironment, improve bioavailability, and provide more personalized disease treatment [12].…”

Section: Introductionmentioning

confidence: 99%

“…However, the topical delivery system of titanium implants allows higher concentrations of antibiotics to penetrate the biofilm and bone tissue, solving the above problems to some extent [12,13]. Compared with systemic drug delivery systems, the advantages of topical drug delivery systems on titanium implants are that they can provide better drug concentrations in the bone microenvironment, improve bioavailability, and provide more personalized disease treatment [12].…”

Section: Introductionmentioning

confidence: 99%

In vitro application of drug-loaded hydrogel combined with 3D-printed porous scaffolds

Huang

Wu²,

Yang³

et al. 2022

Biomed. Mater.

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The two main causes of implant surgery failure are aseptic loosening and bacterial-induced implant-associated infections. To make bone defect implants effective for a long time, the ideal scaffold should take into account the two functions of osseointegration and anti-infection. Therefore, on the basis of the low-elastic-modulus Ti-10Ta-2Nb-2Zr (TTNZ) alloys developed by the research group in the early stage, this study intends to combine the vancomycin-loaded hydrogel with the 3D-printed through-hole porous titanium alloy scaffold to endow 3D-printed TTNZ scaffolds with antibac-terial properties. The local release rate of vancomycin and the effect of this composite system on osseointegration from the aspects of cell adhesion, cell proliferation, osteogenesis-related gene expression, and the antibacterial properties were investigated by the inhibition zone test and the adhesion/free antibacterial test. The results showed that loading 2.5 wt.% and 5 wt.% vancomycin did not affect the structure of chitosan–hyaluronic acid hydrogel. The properties of the hydrogels were examined by scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR), and vancomycin release experiments in vitro. When combined with porous scaffolds, the drug-loaded hydrogels exhibited slower drug release rates and longer release times. In addition, in vitro studies found that the TTNZ scaffolds loaded with 5 wt.% vancomycin had a certain effect on the expression of osteogenesis-related genes in cells, but the antibacterial effect was the best. The porous scaffolds loaded with 2.5 wt.% vancomycin hydrogel TTNZ scaffolds did not inhibit cell proliferation, adhesion, alkaline phosphatase activity, and osteogenesis-related gene expression, but the antibacterial effect on free bacteria was not as good as that of TTNZ scaffolds loaded with 5 wt.% vancomycin. This study, complementing the advantages of the two and controlling the local release rate of vancomycin, provides a new idea for future 3D printing of titanium alloy stents for anti-infection.

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“…Long-term intravenous or oral antibiotics are the main traditional approaches to treat bacterial infection after implant surgery 13 , which have severe drawbacks including harmful side effects, toxicity, uneven bio-distribution, and less bioavailability 14 , 15 . Staphylococcus aureus is considered the main bacteria that causes implant infection after surgery 16 – 18 .…”

Section: Introductionmentioning

confidence: 99%

Effect of electrochemical oxidation and drug loading on the antibacterial properties and cell biocompatibility of titanium substrates

Nowruzi

Imani

Faghihi

2022

Sci Rep

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A combination of $${\text{ TiO}}_{2}$$ TiO 2 nanotube array (TON) and controlled drug release system is employed to provide enhanced surface properties of titanium implants. Electrochemical anodization process is used to generate TON for introducing, vancomycin, an effective antibacterial drug against Staphylococcusaureus. TON loaded vancomycin is then coated with a number of layers of 10% gelatin using spin coating technique. The gelatin film is reinforced with graphene oxide (GO) nanoparticles to improve the surface bioactivity. The surface of the samples is characterized by field emission electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), and contact angle measurement. The results illustrate that the TON was constructed and vancomycin molecules are successfully loaded. The drug release study shows that the amount of released vancomycin is controlled by the thickness of gelatin layers. With an increase in gelatin film layers from 3 to 7, the release of vancomycin in the burst release phase decreased from 58 to 31%, and sustained release extended from 10 to 17 days. The addition of GO nanoparticles seems to reduce drug release in from 31 to 22% (burst release phase) and prolonged drug release (from 17 to 19 days). MTT assay indicates that samples show no cytotoxicity, and combination of GO nanoparticles with gelatin coating could highly promote MG63 cell proliferation. Soaking the samples in SBF solution after 3 and 7 days demonstrates that hydroxy apatite crystals were deposited on the TON surface with GO-gelatin coating more than surface of TON with gelatin. Moreover, based on the results of disc diffusion assay, both samples (loaded with Vancomycin and coated with gelatin and gelatin-GO) with the inhibition zones equaled to 20 mm show effective antibacterial properties against S. aureus. The evidence demonstrates that titania nanotube loaded with vancomycin and coated with gelatin-GO has a great potential for general applicability to the orthopedic implant field.

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Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics

Cited by 20 publications

References 127 publications

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

Radiolabeled Risperidone microSPECT/CT Imaging for Intranasal Implant Studies Development

In vitro application of drug-loaded hydrogel combined with 3D-printed porous scaffolds

Effect of electrochemical oxidation and drug loading on the antibacterial properties and cell biocompatibility of titanium substrates

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