Comprehensive Appraisal of Graphene–Oxide Ratio in Porous Biopolymer Hybrids Targeting Bone-Tissue Regeneration

The bone-tissue engineering (BTE) field is continuously growing due to a major need for bone substitutes in cases of serious traumas, when the bone tissue has reduced capacity for self-regeneration. So far, graphene oxide (GO)-reinforced natural materials provide satisfactory results for BTE, for both in vitro and in vivo conditions. In this study, we aimed to evaluate the biocompatibility of a new biocomposite consisting of chitosan and fish gelatin crosslinked with genipin and loaded with various concentrations of GO (0.5, 1, 2, 3 wt.%) for prospective BTE applications. Scaffold characterizations revealed a constant swelling degree and good resistance to enzyme degradation. The composites presented a porous structure with pores of similar size, thus mimicking the bone structure. In vitro biocompatibility assays demonstrated an overall beneficial interaction between preosteoblasts, and these particular composites, particularly with 0.5 wt.% GO, reinforced composition. Next, the materials were implanted subcutaneously in 6-week old CD1 mice for in vivo evaluation of biocompatibility and inflammatory activity. Immunohistochemical staining revealed maximal cell infiltration and minimal inflammatory reaction for fish gelatin/chitosan/genipin with 0.5 wt.% GO scaffold, thus demonstrating the best biocompatibility for this particular composition, confirming the in vitro results. This study revealed the potential use of fish gelatin/chitosan GO composites for further implementation in the BTE field.

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Scaffolds containing chitosan, gelatin and graphene oxide for bone tissue regeneration in vitro and in vivo

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2017.01.034 ◽

2017 ◽

Vol 104 ◽

pp. 1975-1985 ◽

Cited By ~ 78

Author(s):

S. Saravanan ◽

Anjali Chawla ◽

M. Vairamani ◽

T.P. Sastry ◽

K.S. Subramanian ◽

...

Keyword(s):

Graphene Oxide ◽

Bone Tissue ◽

Tissue Regeneration ◽

Bone Tissue Regeneration ◽

Regeneration In Vitro

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Silicate-doped nano-hydroxyapatite/graphene oxide composite reinforced fibrous scaffolds for bone tissue engineering

Journal of Biomaterials Applications ◽

10.1177/0885328218763665 ◽

2018 ◽

Vol 32 (10) ◽

pp. 1392-1405 ◽

Cited By ~ 15

Author(s):

Ali Deniz Dalgic ◽

Ammar Z. Alshemary ◽

Ayşen Tezcaner ◽

Dilek Keskin ◽

Zafer Evis

Keyword(s):

Tissue Engineering ◽

Graphene Oxide ◽

Bone Tissue Engineering ◽

Protein Adsorption ◽

Bone Tissue ◽

Three Dimensional ◽

Osteosarcoma Cell ◽

In Vitro Biocompatibility ◽

Microscopy Techniques

In this study, novel graphene oxide–incorporated silicate-doped nano-hydroxyapatite composites were prepared and their potential use for bone tissue engineering was investigated by developing an electrospun poly(ε-caprolactone) scaffold. Nanocomposite groups were synthesized to have two different ratios of graphene oxide (2 and 4 wt%) to evaluate the effect of graphene oxide incorporation and groups with different silicate-doped nano-hydroxyapatite content was prepared to investigate optimum concentrations of both silicate-doped nano-hydroxyapatite and graphene oxide. Three-dimensional poly(ε-caprolactone) scaffolds were prepared by wet electrospinning and reinforced with silicate-doped nano-hydroxyapatite/graphene oxide nanocomposite groups to improve bone regeneration potency. Microstructural and chemical characteristics of the scaffolds were investigated by X-ray diffraction, Fourier transform infrared spectroscope and scanning electron microscopy techniques. Protein adsorption and desorption on material surfaces were studied using fetal bovine serum. Presence of graphene oxide in the scaffold, dramatically increased the protein adsorption with decreased desorption. In vitro biocompatibility studies were conducted using human osteosarcoma cell line (Saos-2). Electrospun scaffold group that was prepared with effective concentrations of silicate-doped nano-hydroxyapatite and graphene oxide particles (poly(ε-caprolactone) – 10% silicate-doped nano-hydroxyapatite – 4% graphene oxide) showed improved adhesion, spreading, proliferation and alkaline phosphatase activity compared to other scaffold groups.

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Design and development of Biomimetic electrospun Sulphonated polyether ether ketone Nanofibrous scaffold for bone tissue regeneration applications: In vitro and In vivo study

Journal of Biomaterials Science Polymer Edition ◽

10.1080/09205063.2022.2025637 ◽

2022 ◽

pp. 1-24

Author(s):

Rajalakshmi Ekambaram ◽

Sangeetha Dharmalingam

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Nanofibrous Scaffold ◽

Bone Tissue Regeneration ◽

In Vivo Study ◽

Design And Development ◽

Polyether Ether Ketone ◽

Ether Ketone

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Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Journal of Tissue Engineering ◽

10.1177/2041731417712073 ◽

2017 ◽

Vol 8 ◽

pp. 204173141771207 ◽

Cited By ~ 28

Author(s):

Mathieu Maisani ◽

Daniele Pezzoli ◽

Olivier Chassande ◽

Diego Mantovani

Keyword(s):

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Critical Issue ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Differentiation Potential ◽

Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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Enhancing in vitro bioactivity and in vivo osteogenesis of organic–inorganic nanofibrous biocomposites with novel bioceramics

Journal of Materials Chemistry B ◽

10.1039/c4tb00889h ◽

2014 ◽

Vol 2 (37) ◽

pp. 6293-6305 ◽

Cited By ~ 15

Author(s):

Tao Liu ◽

Xinbo Ding ◽

Dongzhi Lai ◽

Yongwei Chen ◽

Ridong Zhang ◽

...

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Biological Properties ◽

Bone Tissue Regeneration ◽

In Vitro Bioactivity ◽

Physicochemical And Biological Properties

MGHA-introduced, an electrospun SF-based composite can exhibit improved physicochemical and biological properties to stimulate bone tissue regeneration and repair.

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In vitro and in vivo evaluation of the marine sponge skeleton as a bone mimicking biomaterial

Integrative Biology ◽

10.1039/c4ib00289j ◽

2015 ◽

Vol 7 (2) ◽

pp. 250-262 ◽

Cited By ~ 25

Author(s):

Samit K. Nandi ◽

Biswanath Kundu ◽

Arnab Mahato ◽

Narsinh L. Thakur ◽

Siddhartha N. Joardar ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Marine Sponge ◽

Marine Sponges ◽

In Vivo Evaluation

This investigation was carried out to identify and characterize marine sponges as potential bioscaffolds in bone tissue engineering.

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Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

10.26434/chemrxiv.13166717 ◽

2020 ◽

Author(s):

Miaomiao He ◽

Ce zhu ◽

Huan Xu ◽

dan Sun ◽

Chen Chen ◽

...

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Bone Repair ◽

Graphene Nanosheets ◽

Biomechanical Properties ◽

Bone Diseases ◽

Bone Tissue Regeneration ◽

Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

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Staphylococcus aureus infects osteoclasts and replicates intracellularly

10.1101/638528 ◽

2019 ◽

Author(s):

Jennifer L Krauss ◽

Philip M Roper ◽

Anna Ballard ◽

Chien-Cheng Shih ◽

James AJ Fitzpatrick ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Confocal Microscopy ◽

Bone Tissue ◽

Post Infection ◽

Bone Structure ◽

High Rate ◽

Therapeutic Interventions ◽

Intracellular Infection

AbstractOsteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. The majority of OM is caused by Staphylococcus aureus, and even with proper treatment, OM has a high rate of recurrence and chronicity. While S. aureus has been shown to infect osteoblasts, persist intracellularly, and promote the release of pro-osteoclastogenic cytokines, it remains unclear whether osteoclasts (OCs) are also a target of intracellular infection. In this study, we examined the interaction between S. aureus and OCs, demonstrating internalization of GFP-labeled bacteria by confocal microscopy, both in vitro and in vivo. Utilizing an intracellular survival assay and flow cytometry during OC differentiation from bone marrow macrophages (BMMs), we found that the intracellular burden of S. aureus increases after initial infection in cells with at least 2 days of exposure to the osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL). Presence of dividing bacteria was confirmed via visualization by transmission electron microscopy. In contrast, undifferentiated BMMs, or those treated with interferon-γ or IL-4, had fewer internal bacteria, or no change, respectively, at 18 hours post infection, compared to 1.5 hours post infection. To further explore the signals downstream of RANKL, we manipulated NFATc1 and alternative NF-κB, which controls NFATc1 and other factors affecting OC function, finding that intracellular bacterial growth correlates with NFATc1 levels in RANKL-treated cells. Confocal microscopy in mature OCs showed a range of intracellular infection that correlated inversely with S. aureus and phagolysosome colocalization. The ability of OCs to become infected, paired with their diminished bactericidal capacity compared to BMMs, could promote OM progression by allowing S. aureus to evade initial immune regulation and proliferate at the periphery of lesions where OCs and bone remodeling are most abundant.Author SummaryThe inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium Staphylococcus aureus. To date, the bone building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone resorbing cells, osteoclasts, participate. In this study, we show that S. aureus can infect osteoclasts and proliferate inside these cells, whereas macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system. Therapeutic interventions that target osteoclasts specifically might reduce the severity of OM or improve antibiotic responses.

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Natural and Synthetic Polymers for Bone Scaffolds Optimization

Polymers ◽

10.3390/polym12040905 ◽

2020 ◽

Vol 12 (4) ◽

pp. 905 ◽

Cited By ~ 15

Author(s):

Francesca Donnaloja ◽

Emanuela Jacchetti ◽

Monica Soncini ◽

Manuela T. Raimondi

Keyword(s):

Tissue Engineering ◽

Bone Tissue ◽

Bone Cells ◽

The Body ◽

Bone Tissue Regeneration ◽

In Vivo Models ◽

Polymeric Scaffold ◽

Technology Improvement

Bone tissue is the structural component of the body, which allows locomotion, protects vital internal organs, and provides the maintenance of mineral homeostasis. Several bone-related pathologies generate critical-size bone defects that our organism is not able to heal spontaneously and require a therapeutic action. Conventional therapies span from pharmacological to interventional methodologies, all of them characterized by several drawbacks. To circumvent these effects, tissue engineering and regenerative medicine are innovative and promising approaches that exploit the capability of bone progenitors, especially mesenchymal stem cells, to differentiate into functional bone cells. So far, several materials have been tested in order to guarantee the specific requirements for bone tissue regeneration, ranging from the material biocompatibility to the ideal 3D bone-like architectural structure. In this review, we analyse the state-of-the-art of the most widespread polymeric scaffold materials and their application in in vitro and in vivo models, in order to evaluate their usability in the field of bone tissue engineering. Here, we will present several adopted strategies in scaffold production, from the different combination of materials, to chemical factor inclusion, embedding of cells, and manufacturing technology improvement.

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