Original Article
From implantation to degradation — are poly (l-lactide)/multiwall carbon nanotube composite materials really cytocompatible?

https://doi.org/10.1016/j.nano.2013.12.012Get rights and content

Abstract

Poly (l-lactide)'s (PLLA) biodegradable properties are of special value in orthopaedic applications, but its mechanical strength limits its usage. To overcome this PLLA can be reinforced by multiwall carbon nanotubes (MWCNT). In this study the PLLA and MWCNT were combined to prepare nanostructured composites (nanocomposite) at 0, 0.1, 0.5 and 1 wt.% reinforcement. The in vitro biocompatibility of these PLLA/MWCNT nanocomposites was evaluated taking into account the various stages of implantation including nanocomposite degradation. PLLA/MWCNT nanocomposites were highly biocompatible with human bone marrow stromal cells (HBMC). The potential surface degradation product, MWCNT, did not induce toxic responses on HBMC. However, the combination of MWCNT with lactic acid, resembling release after bulk degradation, significantly inhibited HBMC proliferation and activity. This study demonstrates the importance of comprehensive evaluations of novel materials for medical applications in predicting possible adverse effects during nanocomposite degradation.

From the Clinical Editor

This study scrutinizes the cytocompatibility of poly-L-lactide reinforced by multiwall carbon nanotubes, and concludes that the combination of MWCNT with lactic acid significantly inhibited human bone marrow stromal cell proliferation and activity, highlighting the importance of comprehensive evaluations of novel materials.

Graphical Abstract

In this study a possible cell–materials interaction occurring after biomaterial implantation was evaluated in respect to PLLA/MWCNT nanocomposite and human cells. No cytotoxic compounds were released from nanocomposites as evaluated by extract test. The material was found to be biocompatible for human bone marrow stromal cells (HBMC adhesion, proliferation, activation and differentiation). The MWCNT that may be released during nanocomposite degradation did not induce adverse responses in HBMC. However, the MWCNT and lactic acid, possible nanocomposite degradation products, revealed to be cytotoxic for HBMC in a synergistic way.

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Section snippets

Nanocomposite preparation

PLLA/MWCNT nanocomposites containing different concentrations of nanotubes (0.1, 0.5 and 1.0 wt.%) were prepared by a melt-blending method in a Brabender Plasticorder PL2000 at 50 rpm as previously described.16 To avoid crystals development during nanocomposite preparation, all samples were directly quenched in iced water bath.17 This allowed keeping the sample crystallinity at the level of 3.3%-9.6% and consequently had low contribution in the modification of the surface roughness. PLLA of

Mechanical properties and surface morphology

Neat PLLA showed stiff and semi-ductile behaviour with a fracture strain at 14.9% (Figure 1, A). The addition of 0.1, 0.5 and 1% of MWCNT to PLLA increased the tensile modulus and decreased elongation at break. The Young's modulus [E] increased from 1451 MPa for neat PLLA to around 1640 MPa for PLLA/MWCNT, demonstrating the reinforcing effect of carbon nanotubes. However, this characteristic was accompanied by an increase of the nanocomposite brittleness as demonstrated by lower values for the

Discussion

Poly (l-lactide) is a Food and Drug Administration (FDA) approved degradable implant material whose application, due to its poor mechanical properties, is limited to the treatment of non-load bearing small bone damage (reviewed in20, 21, 22). Here we describe the effects of the addition of MWCNT to PLLA regarding the in vitro biological effects of such nanocomposites.

Carbon nanotubes are promising reinforcements for the development of lightweight and stiff materials due to their unusual Young's

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      In addition to nanocarbon materials, the combined degradation product of polymer and carbon may be toxic. The combination of mwCNT and lactic acid, the degradation product of PLA, showed inhibition to the activity of human bone marrow stromal cells although free-dispersed mwCNT did not show cytotoxicity in the same study [298]. Considering the superior electrical and mechanical properties of nanocarbons and great potential on mitigated toxicity and biodegradation of the composite [299,300], polymer-carbon electrospun composite would be a promising scaffold for tissue engineering.

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    Statement disclosure: The authors disclose any commercial associations, current and within the past five years, that might pose a potential, perceived or real conflict of interest.

    This work was supported by funds of the European Community of Seventh Framework Programme, Theme NMP-2007-2.1-1: Nanostructured polymer-matrix composites (POCO), grant agreement no.: CP-IP 213939-1. The postdoctoral fellowship of E. L. was supported by University of the Basque Country (UPV/EHU).

    Prior presentations of abstract at meetings: This work was presented in the form of an oral presentation at SSB meeting 2013 in Davos and as a poster on the ESB conference 2013 in Madrid.

    We thank Purac (NL) for kindly providing the lactic acid.

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