Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets

Sá, Marcos Augusto de; Andrade, Vanessa Barbosa; Mendes, Renato M.; Caliari, Marcelo Vidigal; Ladeira, Luiz Orlando; Silva, E E; Silva, G A B; Corrêa-Júnior, J D; Ferreira, Anderson J.

doi:10.1111/odi.12030

Cited by 34 publications

(19 citation statements)

References 24 publications

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“…HY-CNTs have been reported to accelerate the bone repair process in rats following an interval of 7 days after extraction of the upper first molar, when applied to the tooth sockets (9). They have also been shown to enhance bone repair in the tooth sockets of diabetic rats, suggesting usefulness in therapies for bone reconstruction in adverse metabolic states (10). CNTs are allotropic forms of carbon in which a hexagonal matrix is arranged along cylindrical surfaces with diameters on the order of nanometers and lengths on the order of micrometers.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

Joviano‐Santos

Maria

Almeida

et al. 2014

Braz J Med Biol Res

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It has been demonstrated that carbon nanotubes (CNTs) associated with sodium hyaluronate (HY-CNTs) accelerate bone repair in the tooth sockets of rats. Before clinical application of HY-CNTs, it is important to assess their biocompatibility. Moreover, cardiac toxicity may be caused by the translocation of these particles to the blood stream. The aim of this study was to evaluate possible changes in cardiovascular function in male Wistar rats whose tooth sockets were treated with either CNTs or HY-CNTs (100 μg/mL, 0.1 mL). Blood pressure and heart rate were monitored in conscious rats 7 days after treatment. Cardiac function was evaluated using the Langendorff perfusion technique. The data showed no changes in blood pressure or heart rate in rats treated with either CNTs or HY-CNTs, and no significant changes in cardiac function were found in any of the groups. To confirm these findings, experiments were conducted in rats injected intraperitoneally with a high concentration of either CNTs or HY-CNTs (0.75 mg/kg). The same parameters were analyzed and similar results were observed. The results obtained 7 days following injection indicate that the administration of low concentrations of CNTs or HY-CNTs directly into tooth sockets did not cause any significant change in cardiovascular function in the rats. The present findings support the possibility of using these biocomposites in humans.

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Section: Introductionmentioning

confidence: 99%

Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

Joviano‐Santos

Maria

Almeida

et al. 2014

Braz J Med Biol Res

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“…[17][18][19] In addition, in closely related bioengineering fields, chemically modified CNTs alone or in combination with distinct composite materials have been applied to facilitate neuronal growth, cartilage, and myocardial tissue differentiation, among other applications. [20][21][22][23][24][25][26][27][28][29][30][31][32] Furthermore, CNTs in suspension have also been investigated as potential carriers for drug delivery, and have been shown to have no effect on vital functions of cells. 31,32 In the current work, we have evaluated the bone-inducing properties of carboxyl (COOH)-modified CNTs by conducting in vitro experiments on two models of progenitor cells, human fetal osteoblasts (hFOBs) and murine embryonic stem cells (mESCs), and we have further investigated bone induction in vivo in a rat model.…”

Section: Introductionmentioning

confidence: 99%

Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

Barrientos‐Durán¹,

Carpenter²,

Nieden³

et al. 2014

IJN

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The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH–SWCNTs) were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH–SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH–SWCNTs’ use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 μg/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the combination of demineralized bone matrix or cartilage particles with SWCNTs were implanted into nude rats, and ectopic bone formation was analyzed. Histological analysis of both types of implants showed high permeability and pore connectivity of the carbon nanotube-soaked implants. Numerous vascularization channels appeared in the formed tissue, additional progenitor cells were recruited, and areas of de novo ossification were found 4 weeks post-implantation. Induction of the expression of bone-related genes and the presence of secreted osteopontin protein were also confirmed by quantitative polymerase chain reaction analysis and immunofluorescence, respectively. In summary, these results are in line with prior contributions that highlight the suitability of SWCNTs as scaffolds with high bone-inducing capabilities both in vitro and in vivo, confirming them as alternatives to current bone-repair therapies.

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“…Corroborating these findings, it has been reported that HY and HY-SWCNTs accelerate the bone repair of tooth sockets of normal and diabetic rats [Mendes et al, 2008;Sá et al, 2013]. Nevertheless, these studies were performed using tooth sockets as a model for bone defect, which is a very small defect in a spongy bone.…”

Section: Discussionmentioning

confidence: 91%

“…In this context, we have previously demonstrated that HY and HY-CNTs were able to accelerate the healing process of tooth sockets of normal and diabetic rats after tooth extraction [Mendes et al, 2008;Sá et al, 2013;Martins-Júnior et al, 2016] without any significant changes in the cardiovascular function of animals [Joviano-Santos et al, 2014]. These studies were performed using tooth sockets as a model for bone repair, which is a very small area in a spongy bone.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Bone Healing by Local Administration of Carbon Nanotubes Functionalized with Sodium Hyaluronate in Rat Tibiae

Andrade

Sá

Mendes

et al. 2017

Cells Tissues Organs

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It has been reported that carbon nanotubes (CNTs) serve as nucleation sites for the deposition of bone matrix and cell proliferation. Here, we evaluated the effects of multi-walled CNTs (MWCNTs) on bone repair of rat tibiae. Furthermore, because sodium hyaluronate (HY) accelerates bone restoration, we associated CNTs with HY (HY-MWCNTs) in an attempt to boost bone repair. The bone defect was created by a 1.6-mm-diameter drill. After 7 and 14 days, tibiae were processed for histological and morphometric analyses. Immunohistochemistry was used to evaluate the expression of vascular endothelial growth factor (VEGF) in bone defects. Expression of osteocalcin (OCN), bone morphogenetic protein-2 (BMP-2), and collagen I (Col I) was assessed by real-time PCR. Histomorphometric analysis showed a similar increase in the percentage of bone trabeculae in tibia bone defects treated with HY and HY-MWCNTs, and both groups presented more organized and thicker bone trabeculae than nontreated defects. Tibiae treated with MWCNTs or HY- MWCNTs showed a higher expression of VEGF. Treatment with MWCNTs or HY-MWCNTs increased the expression of molecules involved in the bone repair process, such as OCN and BMP-2. Also, HY- and MWCNT-treated tibiae had an increased expression of Col I. Thus, it is tempting to conclude that CNTs associated or not with other materials such as HY emerged as a promising biomaterial for bone tissue engineering.

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Carbon nanotubes functionalized with sodium hyaluronate restore bone repair in diabetic rat sockets

Abstract: Our results indicate that HY and HY-CNT restore bone repair in the tooth sockets of diabetic rats, suggesting that these biomaterials are potential adjuvant therapies for the management of diabetes.

Cited by 34 publications

References 24 publications

Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

Evaluation of cardiovascular toxicity of carbon nanotubes functionalized with sodium hyaluronate in oral regenerative medicine

Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

Enhancement of Bone Healing by Local Administration of Carbon Nanotubes Functionalized with Sodium Hyaluronate in Rat Tibiae

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