A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement

https://doi.org/10.1016/j.jmbbm.2017.08.017Get rights and content

Highlights

  • Calcium phosphate cements were reinforced with chitosan fibers and soluble chitosan.

  • The chemical affinity of fibers and matrix improved interfacial adhesion.

  • Mechanical reinforcement was achieved thanks to a good fiber-matrix adhesion.

  • Fiber-reinforced cements were significantly tougher than non-reinforced analogues.

  • The modified cement matrix supported osteoblast proliferation.

Abstract

Calcium phosphate cements (CPCs) are extensively used as synthetic bone grafts, but their poor toughness limits their use to non-load-bearing applications. Reinforcement through introduction of fibers and yarns has been evaluated in various studies but always resulted in a decrease in elastic modulus or bending strength when compared to the CPC matrix. The aim of the present work was to improve the interfacial adhesion between fibers and matrix to obtain tougher biocompatible fiber-reinforced calcium phosphate cements (FRCPCs). This was done by adding a polymer solution to the matrix, with chemical affinity to the reinforcing chitosan fibers, namely trimethyl chitosan (TMC). The improved wettability and chemical affinity of the chitosan fibers with the TMC in the liquid phase led to an enhancement of the interfacial adhesion. This resulted in an increase of the work of fracture (several hundred-fold increase), while the elastic modulus and bending strength were maintained similar to the materials without additives. Additionally the TMC-modified CPCs showed suitable biocompatibility with an osteoblastic cell line.

Introduction

Calcium phosphate cements (CPCs) are ceramic materials, brittle by definition, with a porosity that can vary between 10% and 50% depending mainly on the liquid to powder ratio used in their preparation (Espanol et al., 2009). The intrinsic brittleness derived from the microstructure and composition of these materials is one of the major limitations of their mechanical performance and has restricted their indication of use to non-load-bearing applications.

The toughness of CPCs ranges from 0.010 to 0.050 kJ/m2 in their work of fracture (WOF) (Canal and Ginebra, 2011), which is far below the work of fracture of bone, reported to be between 1.5 and 15 kJ/m2 (Currey and Butler, 1975). Although the bending strength values reported for CPCs are typically in the range of 5–15 MPa (Martin and Brown, 1995, Ginebra et al., 2001), close to that of trabecular bone (estimated between 10 and 20 MPa) (Barinov, 2010), their strain to failure is much lower (Xu et al., 2002). The brittleness of CPCs has recently been highlighted in a report on their strain-to-crack-initiation, which amounted to a mere 0.2% in compression (Ajaxon et al., 2017). An improvement of the mechanical performance of these materials, and particularly a mitigation of their brittle behavior, would significantly extend the applicability of CPCs.

For the last 15 years, several strategies have been evaluated to reinforce CPCs with fibers (Canal and Ginebra, 2011, Krüger and Groll, 2012). Fibers have been incorporated to the CPC matrix using different lengths (Xu et al., 2000, Pan et al., 2007), aspect ratios (diameter/length) (Xu et al., 2000, Zhang and Xu, 2005, Zuo et al., 2010), orientations and textile constructs (mono/multifilaments, yarns, nonwovens, etc.) as reviewed by Canal and Ginebra (2011). These approaches have allowed either an increase of the mechanical properties (Zhang and Xu, 2005) or to couple good mechanical properties and macroporosity, increasing the degradation rate and allowing cell infiltration in the material (Xu et al., 2006, Xu et al., 2007). Nonetheless, up to now, little attention has been paid to the fiber-matrix adhesion, which is crucial for a successful load transfer, a prerequisite for an effective reinforcement (Nelson et al., 2002). The potential of the strategies based on enhancing the fiber-matrix interface has been highlighted recently by the improvement of the reinforcement of PLA fibers through surface modification of the fibers by cold plasmas (Canal et al., 2014, Maenz et al., 2014).

Polymeric additives have earlier been used in CPCs with the purpose of improving their mechanical properties, injectability, resorption rate and biocompatibility (Dorozhkin, 2009, Neumann and Epple, 2006, Low et al., 2010, Perez et al., 2012, Engstrand et al., 2013). The polymers, which are often biodegradable, can be added to the matrix either solubilized in the liquid phase or as a second phase, as particles or fibers. Among the different polymers, chitosan is of interest mainly because it is biodegradable, biocompatible, and it can be processed into several products including flakes, fine powders, beads, membranes, fibers, and gels (Badawy and Rabea, 2011).

In this work we used a strategy inspired by the acrylic bone cements, which consist of polymethyl methacrylate (PMMA) spheres embedded in a matrix of the same polymer (Ginebra, 2009). The excellent adhesion between the PMMA particles and the PMMA matrix is due to the chemical affinity between the liquid and the solid phase. The methyl methacrylate monomer wets completely the PMMA powder, dissolving and repolymerizing the surface of the particles, creating a perfect continuity between the matrix and the filler. In our case, although it is not possible to induce a partial dissolution of the polymeric fibers due to the hydraulic nature of calcium phosphate cements, an attempt was made to enhance the continuity between fibers and matrix by adding to the cement matrix the same polymer used for the fibers.

Thus, the aim of this work was to develop a biocompatible fiber-reinforced CPC (FRCPC) with improved mechanical properties using chitosan as common polymer in the matrix and in the fibers, with the hypothesis that having an additive of similar nature would increase the chemical interactions between matrix and fibers, which would in turn result in a higher toughness. As chitosan is poorly soluble in water, trimethyl chitosan (TMC), which is a more soluble chitosan derivative (Domard et al., 1986), was added to the cement liquid phase, and chitosan fibers were used as reinforcing agents.

Section snippets

Fiber reinforced calcium phosphate cements

Fiber-reinforced calcium phosphate cements (FRCPCs) were prepared by mixing a solid phase containing α-tricalcium phosphate (α-TCP) and chitosan fibers with a liquid phase. The solid phase consisted of in-house made α-TCP obtained by solid-state reaction of a 2:1 molar mixture of calcium hydrogen phosphate (CaHPO4, Sigma–Aldrich C7263) and calcium carbonate (CaCO3, Sigma–Aldrich C4830) at 1400 °C for 15 h followed by quenching in air. The powder was first milled with 10 balls (d = 30 mm) for 15 min

Physico-chemical characterization

The presence of 1 w/v% TMC in the liquid phase increased the setting time of the cement in comparison with that prepared only with water (Table 2). The pH of a cement slurry (200 ml/g) remained at 7.0–7.5 when 1 w/v% TMC was used as solution. In contrast, when only water was used, the pH increased from ca. 7–9.3 in less than 10 min, followed by a slow decrease to a neutral pH during 24 h (Fig. 1).

The crystalline phases of the end-products of the cementitious reaction were analyzed after 7 days (Fig.

Discussion

Fiber Reinforced Calcium Phosphate Cements (FRCPCs) with improved fiber/matrix adhesion were obtained in this work by introducing a polymeric solution (trimethyl chitosan, TMC) in the cement matrix, with high affinity to the chitosan fibers that were randomly oriented in the matrix.

To the best of our knowledge, only two prior studies aimed to improve the adhesion of the fiber/matrix interface in CPC-fiber composites, but with a different strategy. These studies were based on the activation of

Conclusion

Fiber-reinforced calcium phosphate cements (FRCPCs) have been successfully prepared using trimethyl chitosan as additive in the liquid phase and chitosan fibers as reinforcing agent. The improved wettability of the fibers and its chemical similarity with the liquid phase of the cement enhanced their interfacial adhesion. The FRCPCs had a significantly improved toughness (measured as work of fracture) and at the same time the elastic modulus and bending strength were maintained in comparison to

Acknowledgements

Authors acknowledge the “Generalitat de Catalunya” funding through a FI Scholarship of SG, the MICINN for the Ramon y Cajal fellowship of CC and the financial support in the MAT2015-65601-R project (MINECO/FEDER, EU). The research leading to these results received funding from the European Commission Seventh Framework Programme (FP7/2007–2013) under the Grant agreement no. 241879, through the “Reborne” project and through the Swedish Foundation for International Cooperation in Research and

References (42)

  • H.H.K. Xu et al.

    Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity

    Biomaterials

    (2002)
  • H.H.K. Xu et al.

    Injectable and macroporous calcium phosphate cement scaffold

    Biomaterials

    (2006)
  • H.H.K. Xu et al.

    Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures

    Biomaterials

    (2007)
  • Y. Zuo et al.

    Incorporation of biodegradable electrospun fibers into calcium phosphate cement for bone regeneration

    Acta Biomater.

    (2010)
  • ASTM Standard C1161-02c, 2002 (2008)

    Standard Test Method for Flexural Strength of Advanced Ceramics at Ambient Temperature

    (2008)
  • ASTM Standard C266-89, 1989 (2003)

    Standard Test Method for Time of Setting of Hydraulic-Cement paste by Gillmore Needles

    (2003)
  • M.E.I. Badawy et al.

    A biopolymer chitosan and its derivatives as promising antimicrobial agents against plant pathogens and their applications in crop protection

    Int. J. Carbohydr. Chem.

    (2011)
  • S.M. Barinov

    Calcium phosphate-based ceramic and composite materials for medicine

    Russ. Chem. Rev.

    (2010)
  • J.D. Bumgardner et al.

    Contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium

    J. Biomater. Sci. Polym. Ed.

    (2003)
  • W.D. Callister et al.

    Materials Science and Engineering: An Introduction

    (2013)
  • C. Canal et al.

    Low-pressure plasma treatment of polylactide fibers for enhanced mechanical performance of fiber-reinforced calcium phosphate cements

    Plasma Process. Polym.

    (2014)
  • Cited by (25)

    • Calcium phosphate cements improved by addition of carbonated Hydroxyapatite type B

      2023, Boletin de la Sociedad Espanola de Ceramica y Vidrio
    • Self-assembling of fibers inside an injectable calcium phosphate bone cement: a feasibility study

      2022, Materials Today Chemistry
      Citation Excerpt :

      The SEM analysis performed after 20 h from the cement preparation revealed that the fibers formation inside the dense matrix was quite completed, as shown in Fig. 3-b. For all the compositions enriched with the LMW gelator, the SEM images obtained from fractured surfaces after 7 days of soaking revealed a high number of fibers (see Fig. 3-c,f) well distributed throughout the matrix and located mainly within the pores (see Fig. 3-g). Moreover, fibers appear strongly interwined with each other (see Fig. 3-d,f) and, most importantly, they show an excellent interaction with the platelets of the apatite phase (as visible in Fig. 3-h), a crucial feature for the success of FRCPCs, as reported in literature [28]. However, on increasing hydrogel concentration, a different fibers’ morphology has been evidenced: the presence of bushes of fibers, mainly located into pores, has been observed in cement G2.6 (see Fig. 3-e) together with thin sheets of hydrogel.

    • Toward stronger robocast calcium phosphate scaffolds for bone tissue engineering: A mini-review and meta-analysis

      2022, Biomaterials Advances
      Citation Excerpt :

      Nevertheless, the strength of CPCs is lower than that of sintered calcium phosphate ceramics [147] and the insufficient mechanical properties of CPC scaffolds have once again limited their use to non-load-bearing applications. The existing literature has seen approaches such as incorporation of polymeric drug [148], fiber reinforcement [149,150], extrusion process modification [151] used for strengthening of robocast CPC scaffolds. Future work shall further optimize the self-setting process and cement composition for improved mechanical properties.

    • Toward stronger robocast calcium phosphate scaffolds for bone tissue engineering: A mini-review and meta-analysis

      2021, Materials Science and Engineering C
      Citation Excerpt :

      Nevertheless, the strength of CPCs is lower than that of sintered calcium phosphate ceramics [147] and the insufficient mechanical properties of CPC scaffolds have once again limited their use to non-load-bearing applications. The existing literature has seen approaches such as incorporation of polymeric drug [148], fiber reinforcement [149,150], extrusion process modification [151] used for strengthening of robocast CPC scaffolds. Future work shall further optimize the self-setting process and cement composition for improved mechanical properties.

    • Antibacterial calcium phosphate composite cements reinforced with silver-doped magnesium phosphate (newberyite) micro-platelets

      2020, Journal of the Mechanical Behavior of Biomedical Materials
      Citation Excerpt :

      In ceramic composites, weak matrix-reinforcement interfaces are preferred. In a recent study, trimethyl chitosan with enhanced wettability was used as reinforcements to improve the interfacial adhesion between fibers and CPC matrix (Gallinetti et al., 2017). Interestingly, the elastic modulus and bending strength of the reinforced specimens did not change as compared to the un-reinforced ones.

    • Micro- and macromechanical characterization of the influence of surface-modification of poly(vinyl alcohol) fibers on the reinforcement of calcium phosphate cements

      2020, Journal of the Mechanical Behavior of Biomedical Materials
      Citation Excerpt :

      Boehm et al. was able to significantly improve the bending strength and work-of-fracture (WOF) of CPCs reinforced with carbon fibers surface-functionalized using different oxidation agents compared to CPCs reinforced with untreated carbon fibers (Boehm et al., 2018). Additionally, Gallinetti et al. successfully improved the WOF of CPCs reinforced with chitosan fibers up to 300% by adding trimethyl chitosan to the liquid phase of the cement, thereby improving the wettability and chemical affinity between the fibers and matrix (Gallinetti et al., 2017). However, other research groups experienced only marginal improvement in the mechanical properties of CPCs after functionalizing the surface of degradable fibers via oxygen plasma treatment (Canal et al., 2014; Maenz et al., 2016) or with alendronate groups (Petre et al., 2019a), possibly due to the damaging effect that the surface treatments had on the bulk mechanical properties of the fibers.

    View all citing articles on Scopus
    1

    Both authors contributed equally.

    View full text