Preparation and Characterization of an Injectable and Photo-Responsive Chitosan Methacrylate/Graphene Oxide Hydrogel: Potential Applications in Bone Tissue Adhesion and Repair

As life expectancy continues to increase, the inevitable weakening and rupture of bone tissue have grown as concerns in the medical community, thus leading to the need for adhesive materials suitable for bone repair applications. However, current commercially available adhesives face certain drawbacks that prevent proper tissue repair, such as low biocompatibility, poor adhesion to wet surfaces, and the need for high polymerization temperatures. This work aims to develop an injectable and photo-responsive chitosan methacrylate/graphene oxide (ChiMA/GO) adhesive nanocomposite hydrogel of high biocompatibility that is easy to apply by simple extrusion and that offers the possibility for in situ polymer and physiological temperatures. The nanocomposite was thoroughly characterized spectroscopically, microscopically, rheologically, thermally, and through mechanical, textural, and biological assays to fully evaluate its correct synthesis and functionalization and its performance under physiological conditions that mimic those observed in vivo. In addition, a finite element analysis (FEA) simulation was used to evaluate its performance in femur fractures. Results suggest the material’s potential as a bioadhesive, as it can polymerize at room temperature, shows superior stability in physiological media, and is capable of withstanding loads from body weight and movement. Moreover, the material showed remarkable biocompatibility as evidenced by low hemolytic and intermediate platelet aggregation tendencies, and high cytocompatibility when in contact with osteoblasts. The comprehensive studies presented here strongly suggest that the developed hydrogels are promising alternatives to conventional bone adhesives that might be further tested in vivo in the near future.

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A review of chitosan-, alginate-, and gelatin-based biocomposites for bone tissue engineering

Biomaterials and Tissue Engineering Bulletin ◽

10.33263/bteb534.097109 ◽

2018 ◽

Vol 5 (3-4) ◽

pp. 97-109 ◽

Cited By ~ 1

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bone Repair ◽

Bone Diseases ◽

Natural Polymers ◽

Antimicrobial Substances ◽

Potential Applications

Bone diseases and injuries have a major impact on the quality of life. Classical treatments for bone repair/regeneration/replacement have various disadvantages. Bone tissue engineering (BTE) received a great attention in the last years. Natural polymers are intensively studied in this field due to their properties (biocompatibility, biodegradability, abundance in nature, high processability). Unfortunately, their mechanical properties are poor, which is why synthetic polymers or ceramics are added in order to provide the optimal compressive, elastic or fatigue strength. Moreover, growth factors, vitamins, or antimicrobial substances are also added to enhance the cell behavior (attachment, proliferation, and differentiation). In this review, new scientific results regarding potential applications of chitosan-, alginate-, and gelatin based biocomposites in BTE will be provided, along with their in vitro and/or in vivo tests.

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The Structure–Properties–Cytotoxicity Interplay: A Crucial Pathway to Determining Graphene Oxide Biocompatibility

International Journal of Molecular Sciences ◽

10.3390/ijms22105401 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5401

Author(s):

Marta Dziewięcka ◽

Mirosława Pawlyta ◽

Łukasz Majchrzycki ◽

Katarzyna Balin ◽

Sylwia Barteczko ◽

...

Keyword(s):

Graphene Oxide ◽

Defense Mechanisms ◽

Physicochemical Analysis ◽

Experimental Models ◽

Acheta Domesticus ◽

Synthesis Process ◽

Synthesis Methods ◽

Toxicity Potential ◽

Potential Applications

Interest in graphene oxide nature and potential applications (especially nanocarriers) has resulted in numerous studies, but the results do not lead to clear conclusions. In this paper, graphene oxide is obtained by multiple synthesis methods and generally characterized. The mechanism of GO interaction with the organism is hard to summarize due to its high chemical activity and variability during the synthesis process and in biological buffers’ environments. When assessing the biocompatibility of GO, it is necessary to take into account many factors derived from nanoparticles (structure, morphology, chemical composition) and the organism (species, defense mechanisms, adaptation). This research aims to determine and compare the in vivo toxicity potential of GO samples from various manufacturers. Each GO sample is analyzed in two concentrations and applied with food. The physiological reactions of an easy model Acheta domesticus (cell viability, apoptosis, oxidative defense, DNA damage) during ten-day lasting exposure were observed. This study emphasizes the variability of the GO nature and complements the biocompatibility aspect, especially in the context of various GO-based experimental models. Changes in the cell biomarkers are discussed in light of detailed physicochemical analysis.

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Preliminary in Vivo Evaluation of Bone Healing in Critical Size Bone Defects Implanted with an Injectable Calcium Phosphate Bone Cement (Osteopaste)

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v16i1.1169 ◽

2017 ◽

Vol 16 (1) ◽

Author(s):

Che Nor Zarida Che Seman ◽

Zamzuri Zakaria ◽

Zunariah Buyong ◽

Mohd Shukrimi Awang ◽

Ahmad Razali Md Ralib @ Md Raghib

Keyword(s):

Calcium Phosphate ◽

Bone Cement ◽

Bone Tissue ◽

Bone Repair ◽

Critical Size ◽

Healing Process ◽

Bone Defects ◽

Calcium Phosphate Bone Cement ◽

Rabbit Tibia

Introduction: A novel injectable calcium phosphate bone cement (osteopaste) has been developed. Its potential application in orthopaedics as a filler of bone defects has been studied. The biomaterial was composed of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. The aim of the present study was to evaluate the healing process of osteopaste in rabbit tibia. Materials and method: The implantation procedure was carried out on thirty-nine of New Zealand white rabbits. The in vivo bone formation was investigated by either implanting the Osteopaste, Jectos or MIIG – X3 into a critical size defect (CSD) model in the proximal tibial metaphysis. CSD without treatment served as negative control. After 1 day, 6 and 12 weeks, the rabbits were euthanized, the bone were harvested and subjected for analysis. Results: Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. There was direct contact between osteopaste material and host bone. The new bone was seen bridging the defect. Conclusion: The result showed that Osteopaste could be a new promising biomaterial for bone repair and has a potential in bone tissue engineering.

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Isocyanate Modified GO Shape-Memory Polyurethane Composite

Polymers ◽

10.3390/polym12010118 ◽

2020 ◽

Vol 12 (1) ◽

pp. 118 ◽

Cited By ~ 2

Author(s):

Yuanchi Zhang ◽

Jinlian Hu

Keyword(s):

Graphene Oxide ◽

Minimally Invasive ◽

Shape Memory ◽

Bone Repair ◽

Recovery Process ◽

Invasive Treatment ◽

Element Analysis ◽

Polyurethane Composite ◽

Shape Memory Effects ◽

Shape Memory Polyurethane

Shape-memory composites have benefits for minimally invasive surgery, but their wider applications for bone repair are hindered by conflicts between the mechanical and memory performances, especially at load-bearing locations. In this study, we fabricated a graphene oxide shape-memory polyurethane composite through the chemical combination of graphene oxide and isocyanate, in order to realize satisfactory mechanical and shape-memory effects. As desired, a modulus of ~339 MPa and a shape recovery ratio of 98% were achieved, respectively, in the composite. In addition, finite element analysis demonstrated that, after being implanted in a defective bone through a minimally invasive treatment, where the highest stress was distributed at the implant–bone interface, this composite could offer a generated force during the recovery process. Furthermore, we also discuss the origins of the improved mechanical and memory properties of the composites, which arise from increased net-points and the stable molecular structure inside. Therefore, with its superior structure and properties, we envision that this shape-memory composite can provide new insights toward the practical application of shape-memory polymers and composites in the field of bone repair.

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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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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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Electrospun Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/Graphene Oxide Scaffold: Enhanced Properties and Promoted in Vivo Bone Repair in Rats

ACS Applied Materials & Interfaces ◽

10.1021/acsami.7b14267 ◽

2017 ◽

Vol 9 (49) ◽

pp. 42589-42600 ◽

Cited By ~ 44

Author(s):

Tengfei Zhou ◽

Guo Li ◽

Shiyu Lin ◽

Taoran Tian ◽

Quanquan Ma ◽

...

Keyword(s):

Graphene Oxide ◽

Bone Repair ◽

Enhanced Properties

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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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An ECM-Mimicking, Mesenchymal Stem Cell-Embedded Hybrid Scaffold for Bone Regeneration

BioMed Research International ◽

10.1155/2017/8591073 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Jozafina Haj ◽

Tharwat Haj Khalil ◽

Mizied Falah ◽

Eyal Zussman ◽

Samer Srouji

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Dorsal Side ◽

Human Mscs ◽

Hybrid Scaffold

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.

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Simvastatin-loaded graphene oxide embedded in polycaprolactone-polyurethane nanofibers for bone tissue engineering applications

Journal of Polymer Engineering ◽

10.1515/polyeng-2020-0301 ◽

2021 ◽

Vol 41 (5) ◽

pp. 375-386

Author(s):

Hessam Rezaei ◽

Mostafa Shahrezaee ◽

Marziyeh Jalali Monfared ◽

Sonia Fathi Karkan ◽

Robabehbeygom Ghafelehbashi

Keyword(s):

Mechanical Properties ◽

Tissue Engineering ◽

Graphene Oxide ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bone Repair ◽

Drug Carrier ◽

Absorption Capacity ◽

Tissue Engineering Application

Abstract Here, the role of simvastatin-loaded graphene oxide embedded in polyurethane-polycaprolactone nanofibers for bone tissue engineering has been investigated. The scaffolds were physicochemically and mechanically characterized, and obtained polymeric composites were used as MG-63 cell culture scaffolds. The addition of graphene oxide-simvastatin to nanofibers generates a homogeneous and uniform microstructure as well as a reduction in fiber diameter. Results of water-scaffolds interaction indicated higher hydrophilicity and absorption capacity as a function of graphene oxide addition. Scaffolds’ mechanical properties and physical stability improved after the addition of graphene oxide. Inducing bioactivity after the addition of simvastatin-loaded graphene oxide terminated its capability for hard tissue engineering application, evidenced by microscopy images and phase characterization. Nanofibrous scaffolds could act as a sustained drug carrier. Using the optimal concentration of graphene oxide-simvastatin is necessary to avoid toxic effects on tissue. Results show that the scaffolds are biocompatible to the MG-63 cell and support alkaline phosphatase activity, illustrating their potential use in bone tissue engineering. Briefly, graphene-simvastatin-incorporated in polymeric nanofibers was developed to increase bioactive components’ synergistic effect to induce more bioactivity and improve physical and mechanical properties as well as in vitro interactions for better results in bone repair.

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