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聚己内酯(PCL)、聚乙二醇(PEG)和聚乳酸-羟基乙酸共聚物(PLGA)聚合物对磷酸钙基质中姜黄素释放及骨再生的影响。

Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for and bone regeneration.

作者信息

Bose Susmita, Sarkar Naboneeta, Banerjee Dishary

机构信息

W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164, United States.

出版信息

Mater Today Chem. 2018 Jun;8:110-120. doi: 10.1016/j.mtchem.2018.03.005. Epub 2018 Apr 14.

DOI:10.1016/j.mtchem.2018.03.005
PMID:30480167
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6251318/
Abstract

Calcium phosphate materials are widely used as bone-like scaffolds or coating for metallic hip and knee implants due to their excellent biocompatibility, compositional similarity to natural bone and controllable bioresorbability. Local delivery of drugs or osteogenic factors from scaffolds and implants are required over a desired period of time for an effectual treatment of various musculoskeletal disorders. Curcumin, an antioxidant and anti-inflammatory molecule, enhances osteoblastc activity in addition to its anti-osteoclastic activity. However, due to its poor solubility and high intestinal liver metabolism, it showed limited oral efficacy in various preclinical and clinical studies. To enhance its bioavailability and to provide higher release, we have used poly (ε-caprolactone) (PCL), poly ethylene glycol (PEG) and poly lactide co glycolide (PLGA) as the polymeric system to enable continuous release of curcumin from the hydroxyapatite matrix for 22 days. Additionally, curcumin was incorporated in plasma sprayed hydroxyapatite coated Ti6Al4V substrate to study cell material interaction using human fetal osteoblast (hFOB) cells for load bearing implants. MTT cell viability assay and morphological characterization by FESEM showed highest cell viability with samples coated with curcumin-PCL-PEG. Finally, 3D printed interconnected macro porous β-TCP scaffolds were prepared and curcumin-PCL-PEG was loaded to assess the effects of curcumin on bone regeneration. The presence of curcumin in TCP results in enhanced bone formation after 6 weeks. Complete mineralized bone formation increased from 29.6 % to 44.9% in curcumin-coated scaffolds compared to pure TCP. Results show that local release of curcumin can be designed for both load bearing or non-load bearing implants with the aid of polymers, which can be considered an excellent candidate for wound healing and tissue regeneration applications in bone tissue engineering.

摘要

磷酸钙材料因其优异的生物相容性、与天然骨的成分相似性以及可控的生物可吸收性,被广泛用作金属髋关节和膝关节植入物的骨样支架或涂层。为有效治疗各种肌肉骨骼疾病,需要在一段期望的时间内从支架和植入物中局部递送药物或成骨因子。姜黄素是一种抗氧化和抗炎分子,除了具有抗破骨细胞活性外,还能增强成骨细胞活性。然而,由于其溶解度低和肠道肝脏代谢高,在各种临床前和临床研究中其口服疗效有限。为提高其生物利用度并实现更高的释放,我们使用聚(ε-己内酯)(PCL)、聚乙二醇(PEG)和聚乳酸-羟基乙酸共聚物(PLGA)作为聚合物体系,以使姜黄素从羟基磷灰石基质中持续释放22天。此外,将姜黄素掺入等离子喷涂羟基磷灰石涂层的Ti6Al4V基底中,使用人胎儿成骨细胞(hFOB)研究承重植入物的细胞与材料相互作用。MTT细胞活力测定和场发射扫描电子显微镜(FESEM)的形态学表征显示,姜黄素-PCL-PEG涂层样品的细胞活力最高。最后,制备了3D打印的相互连接的大孔β-磷酸三钙(β-TCP)支架,并加载姜黄素-PCL-PEG以评估姜黄素对骨再生的影响。6周后,TCP中姜黄素的存在导致骨形成增强。与纯TCP相比,姜黄素涂层支架中完全矿化的骨形成从29.6%增加到44.9%。结果表明,借助聚合物可为承重或非承重植入物设计姜黄素的局部释放,这可被视为骨组织工程中伤口愈合和组织再生应用的极佳候选物。

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