Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication,
                    <i>in vitro</i>
                    and
                    <i>in vivo</i>
                    evaluation

Mikael, Paiyz E.; Amini, Ami R.; Basu, Joysurya; Arellano-Jiménez, M. Josefina; Laurencin, Cato T.; Sanders, Mary M.; Carter, C. Barry; Nukavarapu, Syam P.

doi:10.1088/1748-6041/9/3/035001

Cited by 77 publications

(54 citation statements)

References 48 publications

(63 reference statements)

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“…12,13 In the medical field, biomaterials using CNTs are expected to be useful as local drug-delivery systems or scaffolds for promoting and guiding bone-tissue regeneration. Previous reports have shown that CNTs possess good osteoconductivity 14,15 and biocompatibility, 16 as well as excellent affinity for cell adhesion.…”

mentioning

confidence: 99%

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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Exfoliated carbon nanofibers (ExCNFs) are expected to serve as excellent scaffolds for promoting and guiding bone-tissue regeneration. We aimed to enhance the effects of ExCNFs with bone morphogenetic proteins (BMPs) and examine their feasibility and safety in clinical applications using a rat femoral fracture model. Group I (n ¼ 16) animals were implanted with control MedGEL. Group II (n ¼ 17) animals were implanted with MedGEL containing ExCNFs. Group III (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2. Group IV (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2 and ExCNFs. The rats were euthanized after 6 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, and highresolution microcomputerized tomography (micro-CT); the femurs were also subjected to biomechanical and histological analysis. The fusion rates in Group IV (73.3%) were considerably higher than those in Groups I (25. Keywords: exfoliated carbon nanofiber; bone morphogenetic protein; fracture healing; rat femoral fracture model; scaffold Bone morphogenetic proteins (BMPs) are members of the transforming growth factor b superfamily and are powerful osteoinductive molecules. The osteoinductive effects of recombinant human BMPs (rhBMPs) in surgical procedures such as fracture repair, healing of critical-size bone defects, and spinal fusion have been demonstrated in animal models and clinical trials; furthermore, rhBMP-2 and rhBMP-7 have been approved for clinical use. [1][2][3][4][5] Unfortunately, the results of clinical trials show that high doses of BMPs are required to induce adequate bone fusion, as the molecules are soluble and easily diffuse away from the fusion site, becoming inactivated in vivo. 6 In addition, the usefulness of BMPs is limited by their high costs. To address these problems, a number of strategies are being developed to generate safer, less expensive, and more efficacious spinal fusion using rhBMP. However, the efficient immobilization of BMPs onto carriers at low dosage while maintaining desirable in vivo regenerative action remains as a major challenge in bone regeneration research and practice. 7,8 The required rhBMP-2 level in humans, even for the FDA-approved collagen sponge-incorporated treatment, is much higher (over six orders of magnitude greater) than that used for in vitro cell level evaluation and in vivo animal studies. 7,9 Several ongoing investigations aim to develop a scaffold that functions as a delivery vehicle, providing cells with a more controlled and sustained release of bioactive molecules to maintain the local growth factor concentration within the therapeutic range.Carbon nanotubes (CNTs) have received much attention because of their interesting properties, including their exceptional mechanical 10 and high electrical and thermal conductivity, 11 which facilitate their use as reinforcements or additives in materials such as plastics, metals, and ceramics to improve the properties of the materials and introduce nove...

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mentioning

confidence: 99%

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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“…Although other groups have used hydroxyapatite-sintered microspheres and carbon-nanotube reinforced scaffolds, no studies have fully characterized homogenous TCP-encapsulated, microsphere-based scaffold degradation in comparison to the polymer alone [16-18]. …”

Section: Discussionmentioning

confidence: 99%

Material characterization of microsphere-based scaffolds with encapsulated raw materials

Sridharan

Mohan

Berkland

et al. 2016

Materials Science and Engineering: C

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“Raw materials,” or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and β-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated groups were compared to ‘blank’ groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4 weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering.

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“…Finally, PLGA-graphene composite fibers are collected continuously from the bottom of the coagulation bath on a spool. Despite the ability of PLGA to mimic natural ECMs, the clinical application of pure PLGA is hampered due to the poor mechanical properties of PLGA for maintaining a robust 3D structure [9] . PLGA reinforced with graphene may help overcome this limitation [44] .…”

Section: Wet-spinning Of Graphene-plga Biomimetic Fibersmentioning

confidence: 99%

“…As such, the first step is to employ a polymer which can mimic natural extracellular matrix (ECM) to match the mechanical properties of the surrounding tissue and display biochemical cues that influence cell behavior. The FDA approved poly lactic-co-glycolic acid (PLGA) is well known to be biocompatible through the copolymer composition, it has tunable mechanical properties and the biodegradation rate can be adjusted [3,5,[9][10][11] . Here we introduce electrical conductivity to the PLGA fibers, while maintaining or enhancing other important properties.…”

Section: Introductionmentioning

confidence: 99%

High‐Performance Multifunctional Graphene‐PLGA Fibers: Toward Biomimetic and Conducting 3D Scaffolds

Esrafilzadeh

Jalili

Stewart

et al. 2016

Adv Funct Materials

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The development of electrically conducting fibers based on known cytocompatible materials is of interest to those engaged in tissue regeneration using electrical stimulation. Herein, it is demonstrated that with the aid of rheological insights, optimized formulations of graphene containing spinnable poly(lactic-co-glycolic acid) (PLGA) dopes can be made possible. This helps extend the general understanding of the mechanics involved in order to deliberately translate the intrinsic superior electrical and mechanical properties of solutionprocessed graphene into the design process and practical fiber architectural engineering. The as-produced fibers are found to exhibit excellent electrical conductivity and electrochemical performance, good mechanical properties, and cellular affinity. At the highest loading of graphene (24.3 wt%), the conductivity of as-prepared fibers is as high as 150 S m-1 (more than two orders of magnitude higher than the highest conductivity achieved for any type of nanocarbon-PLGA composite fibers) reported previously. Moreover, the Young's modulus and tensile strength of the base fiber are enhanced 647-and 59-folds, respectively, through addition of graphene. Disciplines Engineering | Physical Sciences and Mathematics Publication DetailsEsrafilzadeh, D., Jalili, R., Stewart, E. M., Aboutalebi, S. H., Razal, J. M., Moulton, S. The development of electrically conducting fibers based on known cytocompatible materials is of interest to those engaged in tissue regeneration using electrical stimulation. Herein, we demonstrate that with the aid of rheological insights, optimized formulations of graphene 2 containing spinnable Poly Lactic-co-Glycolic Acid (PLGA) dopes can be made possible. This helps us extend our general understanding of the mechanics involved in order to deliberately translate the intrinsic superior electrical and mechanical properties of solution-processed graphene into the design process and practical fiber architectural engineering. The asproduced fibers were found to exhibit excellent electrical conductivity, and electrochemical performance, good mechanical properties, and cellular affinity. At the highest loading of graphene (24.3 wt. %), the conductivity of as-prepared fibers was as high as 150 S m −1 (more than 2 orders of magnitude higher than the highest conductivity achieved for any type of nanocarbon-PLGA composite fibers) reported previously. Moreover, the Young's modulus and tensile strength of the base fiber were enhanced 647-and 59-folds, respectively, through addition of graphene.

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Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication, in vitro and in vivo evaluation

Cited by 77 publications

References 48 publications

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Material characterization of microsphere-based scaffolds with encapsulated raw materials

High‐Performance Multifunctional Graphene‐PLGA Fibers: Toward Biomimetic and Conducting 3D Scaffolds

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