College of Chemistry, Chemical Engineering and Biotechnology; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University , 2999 North Renmin Road, Shanghai 201620, China.
College of Materials Science and Engineering, Donghua University , Shanghai 201620, China.
ACS Appl Mater Interfaces. 2016 Feb 17;8(6):4137-48. doi: 10.1021/acsami.5b11879. Epub 2016 Feb 5.
The incorporation of microcarriers as drug delivery vehicles into polymeric scaffold for bone regeneration has aroused increasing interest. In this study, the aminated mesoporous silica nanoparticles (MSNs-NH2) were prepared and used as microcarriers for dexamethasone (DEX) loading. Poly(l-lactic acid)/poly(ε-caprolactone) (PLLA/PCL) nanofibrous scaffold was fabricated via thermally induced phase separation (TIPS) and served as template, onto which the drug-loaded MSNs-NH2 nanoparticles were deposited by electrophoretic deposition (EPD). The physicochemical and release properties of the prepared scaffolds (DEX@MSNs-NH2/PLLA/PCL) were examined, and their osteogenic activities were also evaluated through in vitro and in vivo studies. The release of DEX from the scaffolds revealed an initial rapid release followed by a slower and sustained one. The in vitro results indicated that the DEX@MSNs-NH2/PLLA/PCL scaffold exhibited good biocompatibility to rat bone marrow-derived mesenchymal stem cells (BMSCs). Also, BMSCs cultured on the DEX@MSNs-NH2/PLLA/PCL scaffold exhibited a higher degree of osteogenic differentiation than those cultured on PLLA/PCL and MSNs-NH2/PLLA/PCL scaffolds, in terms of alkaline phosphatase (ALP) activity, mineralized matrix formation, and osteocalcin (OCN) expression. Furthermore, the in vivo results in a calvarial defect model of Sprague-Dawley (SD) rats demonstrated that the DEX@MSNs-NH2/PLLA/PCL scaffold could significantly promote calvarial defect healing compared with the PLLA/PCL scaffold. Thus, the EPD technique provides a convenient way to incorporate osteogenic agents-containing microcarriers to polymer scaffold, and thus, prepared composite scaffold could be a potential candidate for bone tissue engineering application due to its capacity for delivery of osteogenic agents.
作为药物递送载体的载药微球被引入到用于骨再生的聚合物支架中,这引起了人们越来越多的兴趣。在这项研究中,制备了氨基化介孔硅纳米粒子(MSNs-NH2),并将其用作地塞米松(DEX)负载的微载体。通过热致相分离(TIPS)制备了聚(L-乳酸)/聚(ε-己内酯)(PLLA/PCL)纳米纤维支架,并用作模板,通过电泳沉积(EPD)将载药的 MSNs-NH2 纳米粒子沉积在其上。制备的支架(DEX@MSNs-NH2/PLLA/PCL)的物理化学性质和释放性能进行了研究,并通过体外和体内研究评估了它们的成骨活性。DEX 从支架中的释放呈现出初始快速释放,随后是缓慢且持续的释放。体外结果表明,DEX@MSNs-NH2/PLLA/PCL 支架对大鼠骨髓间充质干细胞(BMSCs)具有良好的生物相容性。此外,在 DEX@MSNs-NH2/PLLA/PCL 支架上培养的 BMSCs 的碱性磷酸酶(ALP)活性、矿化基质形成和骨钙素(OCN)表达方面,其成骨分化程度高于在 PLLA/PCL 和 MSNs-NH2/PLLA/PCL 支架上培养的 BMSCs。此外,在 Sprague-Dawley(SD)大鼠颅骨缺损模型中的体内结果表明,与 PLLA/PCL 支架相比,DEX@MSNs-NH2/PLLA/PCL 支架能够显著促进颅骨缺损的愈合。因此,EPD 技术为将含有成骨剂的载药微球引入聚合物支架提供了一种简便的方法,因此,由于其能够递送成骨剂,所制备的复合支架可能成为骨组织工程应用的潜在候选材料。