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用于软骨置换的具有可控双氯芬酸释放功能的聚碳酸酯聚氨酯基材料的研发。

Development of polycarbonate urethane-based materials with controlled diclofenac release for cartilage replacement.

作者信息

Oliveira Andreia S, Ferreira Inês, Branco Ana C, Silva João C, Costa Carolina, Nolasco Pedro, Marques Ana C, Silva Diana, Colaço Rogério, Figueiredo-Pina Célio G, Serro Ana P

机构信息

CQE, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

IDMEC e Departamento de Engenharia Mecânica, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

出版信息

J Biomed Mater Res B Appl Biomater. 2022 Aug;110(8):1839-1852. doi: 10.1002/jbm.b.35042. Epub 2022 Feb 28.

DOI:10.1002/jbm.b.35042
PMID:35226412
Abstract

Hydrogels are very promising human cartilage replacement materials since they are able to mimic its structure and properties. Besides, they can be used as platforms for drug delivery to reduce inflammatory postsurgical reactions. Polycarbonate urethane (PCU) has been used in orthopedic applications due to its long-term biocompatibility and bio-durability. In this work, PCU-based hydrogels with the ability to release an anti-inflammatory (diclofenac) were developed, for the first time, for such purpose. The materials were reinforced with different amounts of cellulose acetate (CA, 10%, 15%, and 25% w/w) or carbon nanotubes (CNT, 1% and 2% w/w) in order to improve their mechanical properties. Samples were characterized in terms of compressive and tensile mechanical behavior. It was found that 15% CA and 2% CNT reinforcement led to the best mechanical properties. Thus, these materials were further characterized in terms of morphology, wettability, and friction coefficient (CoF). Contrarily to CNTs, the addition of CA significantly increased the material's porosity. Both materials became more hydrophilic, and the CoF slightly increased for PCU + 15%CA. The materials were loaded by soaking with diclofenac, and drug release experiments were conducted. PCU, PCU + 15%CA and PCU + 2%CNT presented similar release profiles, being able to ensure a controlled release of DFN for at least 4 days. Finally, in vitro cytotoxicity tests using human chondrocytes were also performed and confirmed a high biocompatibility for the three studied materials.

摘要

水凝胶是非常有前景的人体软骨替代材料,因为它们能够模拟软骨的结构和特性。此外,它们还可以用作药物递送平台,以减少术后炎症反应。聚碳酸酯聚氨酯(PCU)因其长期生物相容性和生物耐久性已被用于骨科应用。在这项工作中,首次开发了具有释放抗炎药(双氯芬酸)能力的基于PCU的水凝胶用于此目的。通过添加不同量的醋酸纤维素(CA,10%、15%和25% w/w)或碳纳米管(CNT,1%和2% w/w)来增强材料,以改善其机械性能。对样品进行了压缩和拉伸力学行为表征。发现15% CA和2% CNT增强导致最佳机械性能。因此,进一步对这些材料进行了形态、润湿性和摩擦系数(CoF)方面的表征。与CNT相反,添加CA显著增加了材料的孔隙率。两种材料都变得更亲水,并且PCU + 15%CA的CoF略有增加。通过用双氯芬酸浸泡使材料负载药物,并进行了药物释放实验。PCU、PCU + 15%CA和PCU + 2%CNT呈现出相似的释放曲线,能够确保双氯芬酸至少4天的控释。最后,还使用人软骨细胞进行了体外细胞毒性测试,并证实了这三种研究材料具有高生物相容性。

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