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用于骨再生的新型聚(D,L-乳酸)、超亲水性碳纳米管和纳米羟基磷灰石支架的体外和体内研究

In Vitro and in Vivo Studies of Novel Poly(D,L-lactic acid), Superhydrophilic Carbon Nanotubes, and Nanohydroxyapatite Scaffolds for Bone Regeneration.

作者信息

Siqueira Idalia A W B, Corat Marcus Alexandre F, Cavalcanti Bruno das Neves, Ribeiro Neto Wilson Alves, Martin Airton Abrahao, Bretas Rosario Elida Suman, Marciano Fernanda Roberta, Lobo Anderson Oliveira

机构信息

‡Multidisciplinary Center for Biological Investigation on Laboratory Animal Science (CEMIB), State University of Campinas, Campinas SP 13083-970, Sao Paulo, Brazil.

§Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

出版信息

ACS Appl Mater Interfaces. 2015 May 13;7(18):9385-98. doi: 10.1021/acsami.5b01066. Epub 2015 May 4.

Abstract

Poly(D,L-lactide acid, PDLLA) has been researched for scaffolds in bone regeneration. However, its hydrophobocity and smooth surface impedes its interaction with biological fluid and cell adhesion. To alter the surface characteristics, different surface modification techniques have been developed to facilitate biological application. The present study compared two different routes to produce PDLLA/superhydrophilic vertically aligned carbon nanotubes:nanohydroxyapatite (PDLLA/VACNT-O:nHAp) scaffolds. For this, we used electrodeposition and immersion in simulated body fluid (SBF). Characterization by goniometry, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy confirmed the polymer modifications, the in vitro bioactivity, and biomineralization. Differential scanning calorimetry and thermal gravimetric analyses showed that the inclusion of VACNT-O:nHA probably acts as a nucleating agent increasing the crystallization rate in the neat PDLLA without structural alteration. Our results showed the formation of a dense nHAp layer on all scaffolds after 14 days of immersion in SBF solution; the most intense carbonated nHAp peaks observed in the PDLLA/VACNT-O:nHAp samples suggest higher calcium precipitation compared to the PDLLA control. Both cell viability and alkaline phosphatase assays showed favorable results, because no cytotoxic effects were present and all produced scaffolds were able to induce detectable mineralization. Bone defects were used to evaluate the bone regeneration; the confocal Raman and histological results confirmed high potential for bone applications. In vivo study showed that the PDLLA/VACNT-O:nHAp scaffolds mimicked the immature bone and induced bone remodeling. These findings indicate surface improvement and the applicability of this new nanobiomaterial for bone regenerative medicine.

摘要

聚(D,L-乳酸,PDLLA)已被研究用于骨再生支架。然而,其疏水性和平滑表面阻碍了它与生物流体的相互作用以及细胞黏附。为了改变表面特性,已开发出不同的表面改性技术以促进其生物应用。本研究比较了两种制备PDLLA/超亲水垂直排列碳纳米管:纳米羟基磷灰石(PDLLA/VACNT-O:nHAp)支架的不同方法。为此,我们采用了电沉积法和浸泡在模拟体液(SBF)中的方法。通过测角术、扫描电子显微镜、X射线衍射和红外光谱进行表征,证实了聚合物的改性、体外生物活性和生物矿化。差示扫描量热法和热重分析表明,加入VACNT-O:nHAp可能起到成核剂的作用,提高了纯PDLLA的结晶速率,且无结构改变。我们的结果表明,在SBF溶液中浸泡14天后,所有支架上均形成了致密的nHAp层;与PDLLA对照相比,在PDLLA/VACNT-O:nHAp样品中观察到的最强烈的碳酸化nHAp峰表明钙沉淀更高。细胞活力和碱性磷酸酶测定均显示出良好的结果,因为不存在细胞毒性作用,且所有制备的支架都能够诱导可检测到的矿化。利用骨缺损评估骨再生;共聚焦拉曼光谱和组织学结果证实了其在骨应用方面的高潜力。体内研究表明,PDLLA/VACNT-O:nHAp支架模拟了未成熟骨并诱导了骨重塑。这些发现表明这种新型纳米生物材料的表面得到了改善,适用于骨再生医学。

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