abstract
The risk-benefit balance for carbon nanotubes (CNTs) dictates their clinical fate. To take a step forward at this crossroad it is compulsory to modulate the CNT in vivo biocompatibility and biodegradability via e.g. chemical functionalization. CNT membranes were functionalised combining a Diels-Alder cycloaddition reaction to generate cyclohexene (-C6H10) followed by a mild oxidisation to yield carboxylic acid groups (-COOH). In vitro proliferation and osteogenic differentiation of human osteoblastic cells were maximized on functionalized CNT membranes (p, f-CNTs). The in vivo subcutaneously implanted materials showed a higher biological reactivity, thus inducing a slighter intense inflammatory response compared to non-functionalized CNT membranes (p-CNTs), but still showing a reduced cytotoxicity profile. Moreover, the in vivo biodegradation of CNTs was superior for p, f-CNT membranes, likely mediated by the oxidation-induced myeloperoxidase (MPO) in neutrophil and macrophage inflammatory milieus. This proves the biodegradability faculty of functionalized CNTs, which potentially avoids long-term tissue accumulation and triggering of acute toxicity. On the whole, the proposed Diels-Alder functionalization accounts for the improved CNT biological response in terms of the biocompatibility and biodegradability profiles. Therefore, CNTs can be considered for use in bone tissue engineering without notable toxicological threats.
keywords
MESENCHYMAL STEM-CELLS; SUBCUTANEOUS IMPLANTATION; CYCLOADDITION; ADHESION; MICE; NANOMATERIALS; BIOMATERIALS; OSTEOBLASTS; NANOFIBERS; RESPONSES
subject category
Chemistry; Science & Technology - Other Topics; Materials Science; Physics
authors
Mata, D; Amaral, M; Fernandes, AJS; Colaco, B; Gama, A; Paiva, MC; Gomes, PS; Silva, RF; Fernandes, MH
our authors
Diogo Miguel Rodrigues Marinho da Mata
Post-doc Fellowship
Margarida Isabel dos Santos Amaral
Post-doc Fellowship
Rui Ramos Ferreira e Silva
Associate Professoracknowledgements
This work was developed in the scope of the project CICECO-Aveiro Institute of Materials (Ref. FCT UID/CTM/50011/2013), financed by national funds through the FCT/MEC and co-financed by FEDER under the PT2020 Partnership Agreement. The authors are very grateful to R. F. Araujo (Centre of Chemistry, Univ. of Minho) for the acid-base titration measurements, M. Ferro (Materials and Ceramic Eng. Dept., Univ. of Aveiro) for the TEM observations, F. J. Oliveira (Materials and Ceramic Eng. Dept., Univ. of Aveiro) for the optical profilometry measurements and the assistance of Dr Carlos Sa (Materials Centre, Univ. of Porto) for the XPS analyses.