Zinc-/copper-substituted dicalcium silicate cement: advanced biomaterials with enhanced osteogenesis and long-term antibacterial properties

Zhang, Feng; Zhou, Mingming; Gu, Weizhong; Shen, Zheng; Ma, Xiaohui; Lu, Fengling; Yang, Xianyan; Zheng, Yifeng; Gou, Zhongru

doi:10.1039/c9tb02691f

Cited by 30 publications

(23 citation statements)

References 45 publications

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“…Cu, Co, and Zn were studied here as recognized components of solid osteogenic materials [ 11 , 12 , 13 , 49 ]; however, therapeutic effects of these TMs in cryogel scaffolds toward soft tissues have not been compared to date. The composition of TM-containing cryogels was optimized so that the metal dopants did not show a cytotoxic effect, while they were able to stimulate the proliferative and functional activity of mammalian cells ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Implanted Co-containing borosilicate glass-based scaffolds remarkably enhanced bone regeneration and the vascularized network of the calvarial defective site in rats [ 12 ]. Likewise, Zn incorporation into Ca-silicate-based cements increased the osteostimulative activity of the composite material in a maxillofacial bone defect model in rabbits [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Regenerative Activities of ROS-Modulating Trace Metals in Subcutaneously Implanted Biodegradable Cryogel

Yergeshov

Zoughaib

Ishkaeva

et al. 2022

Gels

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Divalent trace metals (TM), especially copper (Cu), cobalt (Co) and zinc (Zn), are recognized as essential microelements for tissue homeostasis and regeneration. To achieve a balance between therapeutic activity and safety of administered TMs, effective gel formulations of TMs with elucidated regenerative mechanisms are required. We studied in vitro and in vivo effects of biodegradable macroporous cryogels doped with Cu, Co or Zn in a controllable manner. The extracellular ROS generation by metal dopants was assessed and compared with the intracellular effect of soluble TMs. The stimulating ability of TMs in the cryogels for cell proliferation, differentiation and cytokine/growth factor biosynthesis was characterized using HSF and HUVEC primary human cells. Multiple responses of host tissues to the TM-doped cryogels upon subcutaneous implantation were characterized taking into account the rate of biodegradation, production of HIF-1α/matrix metalloproteinases and the appearance of immune cells. Cu and Zn dopants did not disturb the intact skin organization while inducing specific stimulating effects on different skin structures, including vasculature, whereas Co dopant caused a significant reorganization of skin layers, the appearance of multinucleated giant cells, along with intense angiogenesis in the dermis. The results specify and compare the prooxidant and regenerative potential of Cu, Co and Zn-doped biodegradable cryogels and are of particular interest for the development of advanced bioinductive hydrogel materials for controlling angiogenesis and soft tissue growth.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regenerative Activities of ROS-Modulating Trace Metals in Subcutaneously Implanted Biodegradable Cryogel

Yergeshov

Zoughaib

Ishkaeva

et al. 2022

Gels

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“…Ewald et al (2012) [ 34 ] observed an enhancement of the expression of bone-specific proteins in osteoblastic cells seeded on a scaffold loaded with Cu ions. Recently, Zhang et al (2020) [ 35 ] synthesized a Cu-substituted dicalcium silicate cement and showed that the quantitative new bone formation was significantly higher with Cu cement than for undoped cement. Thus, the use of materials doped with copper ions, able to both prevent infections and promote wound healing, represents a promising research subject.…”

Section: Discussionmentioning

confidence: 99%

Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties

et al. 2021

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Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates (x = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in Ca10Cux(PO4)6(OH)2-2xO2x). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and E. coli, releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against P. aeruginosa. This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu2+ were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.

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“…However, the Zn 2+ toxicity level reported in the literature seems to be very close to the maximum concentration of Zn 2+ in GPCA. Studies have indicated that the addition of low levels of Zn in biomaterials enhances cell proliferation and protein synthesis [27,79,80]. Brauer et al showed that the addition of Zn has a dose-dependent effect on the cytotoxicity of GPC, on which the addition of 300 µM of Zn increased mouse osteoblast metabolic activity, while the GPC exposed to 400 µM of Zn showed a reduction in cell metabolic activity [73].…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

Hasandoost

Marx

Zalzal

et al. 2021

JFB

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Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.

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Zinc-/copper-substituted dicalcium silicate cement: advanced biomaterials with enhanced osteogenesis and long-term antibacterial properties

Abstract: Dicalcium silicate (C2S) cements doped with Zn or Cu exhibited appreciable osteogenic activity and prolonged antibacterial potential in comparison with C2S cement.

Cited by 30 publications

References 45 publications

Regenerative Activities of ROS-Modulating Trace Metals in Subcutaneously Implanted Biodegradable Cryogel

Regenerative Activities of ROS-Modulating Trace Metals in Subcutaneously Implanted Biodegradable Cryogel

Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties

Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

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