Mata D, Amaral M, Fernandes A J S, Colaço B, Gama A, Paiva M C, Gomes P S, Silva R F, Fernandes M H
CICECO, Materials and Ceramic Eng. Dept., Univ. of Aveiro, 3810-193 Aveiro, Portugal.
Nanoscale. 2015;7(20):9238-51. doi: 10.1039/c5nr01829c. Epub 2015 Apr 30.
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.
碳纳米管（CNT）的风险效益平衡决定了它们的临床命运。要在这个十字路口向前迈进，必须通过例如化学功能化来调节CNT在体内的生物相容性和生物降解性。通过狄尔斯-阿尔德环加成反应使CNT膜功能化，生成环己烯（-C6H10），然后进行温和氧化以产生羧酸基团（-COOH）。在功能化的CNT膜（p,f-CNTs）上，人成骨细胞的体外增殖和成骨分化达到最大化。与未功能化的CNT膜（p-CNTs）相比，体内皮下植入材料显示出更高的生物反应性，因此诱导的炎症反应稍弱，但细胞毒性仍然较低。此外，p,f-CNT膜的CNT体内生物降解性更好，这可能是由中性粒细胞和巨噬细胞炎症环境中氧化诱导的髓过氧化物酶（MPO）介导的。这证明了功能化CNT的生物降解能力，它有可能避免长期组织积累和急性毒性的触发。总体而言，所提出的狄尔斯-阿尔德功能化在生物相容性和生物降解性方面改善了CNT的生物学反应。因此，可以考虑将CNT用于骨组织工程，而不存在明显的毒理学威胁。
