Chitosan/hydroxyapatite composite bone tissue engineering scaffolds with dual and decoupled therapeutic ion delivery: copper and strontium

Gritsch, Lukas; Maqbool, Muhammad; Mouriño, Viviana; Ciraldo, Francesca E.; Cresswell, Mark; Jackson, Philip; Lovell, Christopher; Boccaccını, Aldo R.

doi:10.1039/c9tb00897g

Cited by 115 publications

(81 citation statements)

References 67 publications

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“…It is clear from the previous findings from the release study that even Cu(II)-CS1 releases sufficient amount of Cu(II) ions within 3 h of incubation, which is greater than the minimal inhibitory concentration (MIC, 10-12 ppm). Moreover, Cu(II) was released up to 24 h, and no further release was observed, which is likely due to the chelation of Cu(II) ions [18]. However, further (long-term) release is also possible due to the enzymatic degradation of CS.…”

Section: Bacterial Culturementioning

confidence: 91%

“…The crystallographic patterns of pure CS and Cu(II)-CS coatings are shown in Figure 4. The XRD pattern of CS coating shows two characteristic broad diffraction peaks at 2θ = 12 o which reveals the amorphous nature, whereas the peak at 2θ = 20 o indicates a high degree of crystallinity in the CS structure [18,38]. However, the XRD pattern shows also two more peaks at 2θ = 51 o and 75 o indicating the presence of the stainless-steel substrate.…”

Section: Chemical and Structural Characterizationmentioning

confidence: 99%

“…Above all, such CS-metal ion complexes are reported to have superior in vitro antibacterial activities as compared to free CS or antimicrobial metal salts [15,16]. Another key advantage of chelation is the ability to release the metal ions from the polymer matrix in a controlled manner [17,18]. Moreover, when choosing the appropriate therapeutic metal ions (TMIs), the chelated complex could assist vital biological processes that include osteogenesis and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Electrophoretic Deposition of Copper(II)–Chitosan Complexes for Antibacterial Coatings

Akhtar

Ilyas

Dlouhý

et al. 2020

IJMS

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Bacterial infection associated with medical implants is a major threat to healthcare. This work reports the fabrication of Copper(II)–Chitosan (Cu(II)–CS) complex coatings deposited by electrophoretic deposition (EPD) as potential antibacterial candidate to combat microorganisms to reduce implant related infections. The successful deposition of Cu(II)–CS complex coatings on stainless steel was confirmed by physicochemical characterizations. Morphological and elemental analyses by scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) spectroscopy verified the uniform distribution of copper in the Chitosan (CS) matrix. Moreover, homogeneous coatings without precipitation of metallic copper were confirmed by X-ray diffraction (XRD) spectroscopy and SEM micrographs. Controlled swelling behavior depicted the chelation of copper with polysaccharide chains that is key to the stability of Cu(II)–CS coatings. All investigated systems exhibited stable degradation rate in phosphate buffered saline (PBS)–lysozyme solution within seven days of incubation. The coatings presented higher mechanical properties with the increase in Cu(II) concentration. The crack-free coatings showed mildly hydrophobic behavior. Antibacterial assays were performed using both Gram-positive and Gram-negative bacteria. Outstanding antibacterial properties of the coatings were confirmed. After 24 h of incubation, cell studies of coatings confirms that up to a certain threshold concentration of Cu(II) were not cytotoxic to human osteoblast-like cells. Overall, our results show that uniform and homogeneous Cu(II)–CS coatings with good antibacterial and enhanced mechanical stability could be successfully deposited by EPD. Such antibiotic-free antibacterial coatings are potential candidates for biomedical implants.

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Section: Bacterial Culturementioning

confidence: 91%

Section: Chemical and Structural Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Electrophoretic Deposition of Copper(II)–Chitosan Complexes for Antibacterial Coatings

Akhtar

Ilyas

Dlouhý

et al. 2020

IJMS

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“…The synthetic scaffold with the predefined properties can be fabricated using nano-hydroxyapatite (n-HA) and chitosan (Ch). This is due to the fact that n-HA is identical to a component of bone [8,9]. The n-HA are bioactive, biodegradable, and osteoconductive, hence widely utilized as an implant and in bone regeneration applications [10,11].…”

Section: Introductionmentioning

confidence: 99%

Study of Mechanical and Thermal Properties in Nano-Hydroxyapatite/Chitosan/Carboxymethyl Cellulose Nanocomposite-Based Scaffold for Bone Tissue Engineering: The Roles of Carboxymethyl Cellulose

et al. 2020

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Synthetic scaffolding for bone tissue engineering (BTE) has been widely utilized. The scaffold for BTE requires sufficient porosity as a template for bone cell development and growth so that it can be used in the treatment of bone defects and fractures. Nevertheless, the porosity significantly influences the compressive strength of the scaffold. Hence, controlling the porosity is a pivotal role to obtain a proper scaffold for practical BTE application. Herein, we fabricated the nanocomposite-based scaffold utilizing nano-hydroxyapatite (n-HA). The scaffold was prepared in combination with chitosan (Ch) and carboxymethyl cellulose (CMC). The ratios of n-HA, Ch, and CMC used were 40:60:0, 40:55:5, 40:50:10, 40:45:15, and 40:40:20, respectively. By controlling the Ch and CMC composition, we can tune the porosity of the nanocomposite. We found that the interpolation of the CMC prevails, as a crosslinker reinforces the nanocomposite. In addition, the binding to Ch enhanced the compressive strength of the scaffold. Thermal characteristics revealed the coefficient of thermal expansion decreases with increasing CMC content. The nanocomposite does not expand at 25–75 °C, which is suitable for human body temperature. Therefore, this nanocomposite-based scaffold is feasible for BTE application.

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“…In this context, our previous studies30 showed how chitosan, a widespread linear polysaccharide of natural origin,31 can be used as an efficient carrier for copper thanks to an intrinsic ability to chelate metal ions 32. The copper ions are successfully incorporated in the polysaccharide matrix and their release can be finely tailored by suitably changing the formulation of the material, as reported in a previous publication 33. Copper(II)‐chitosan has been effectively used as antibiotic‐free antibacterial material against both Gram positive and negative bacteria without significant cytotoxicity against fibroblasts 30.…”

Section: Introductionmentioning

confidence: 87%

Polycaprolactone Electrospun Fiber Mats Prepared Using Benign Solvents: Blending with Copper(II)‐Chitosan Increases the Secretion of Vascular Endothelial Growth Factor in a Bone Marrow Stromal Cell Line

Gritsch

Liverani

Lovell

et al. 2020

Macromolecular Bioscience

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Inducing the formation of new blood vessels (angiogenesis) is an essential requirement for successful tissue engineering. Approaches have been proposed to enhance angiogenesis using growth factors and other biomolecules; however, this approaches present drawbacks in terms of high cost and patient safety. Copper is known to effectively regulate angiogenesis and can offer a more cost‐effective alternative than the direct use of growth factors. With this study, a strategy to incorporate copper in electrospun fibrous scaffolds with pro‐angiogenic properties is presented. Polycaprolactone (PCL) and copper(II)‐chitosan are electrospun using benign solvents. The morphological and physicochemical properties of the fiber mats are investigated through scanning electron microscopy (SEM), static contact angle measurements, energy dispersive X‐ray, and Fourier‐transform infrared spectroscopies. Scaffold stability in phosphate buffered saline at 37 °C is monitored over 1 week. A bone marrow stromal cell line (ST‐2) is cultured for 7 days and its behavior is evaluated using SEM, fluorescence microscopy and a tetrazolium salt‐based colorimetric assay. Results confirm that PCL/copper(II)‐chitosan is suitable for electrospinning. The fiber mats are biocompatible and favor cell colonization and infiltration. Most notably, the angiogenic potential of PCL/copper(II)‐chitosan blends is confirmed by a three‐fold increase in VEGF secretion by ST‐2 cells in the presence of copper(II)‐chitosan.

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Chitosan/hydroxyapatite composite bone tissue engineering scaffolds with dual and decoupled therapeutic ion delivery: copper and strontium

Abstract: Porous composite scaffolds with decoupled ion release of copper and strontium were fabricated and characterized: a reproducible and cost-effective approach to obtain constructs with tailored release profiles and promising biological properties.

Cited by 115 publications

References 67 publications

Electrophoretic Deposition of Copper(II)–Chitosan Complexes for Antibacterial Coatings

Electrophoretic Deposition of Copper(II)–Chitosan Complexes for Antibacterial Coatings

Study of Mechanical and Thermal Properties in Nano-Hydroxyapatite/Chitosan/Carboxymethyl Cellulose Nanocomposite-Based Scaffold for Bone Tissue Engineering: The Roles of Carboxymethyl Cellulose

Polycaprolactone Electrospun Fiber Mats Prepared Using Benign Solvents: Blending with Copper(II)‐Chitosan Increases the Secretion of Vascular Endothelial Growth Factor in a Bone Marrow Stromal Cell Line

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