Singh Rajendra K, Patel Kapil D, Lee Jae Ho, Lee Eun-Jung, Kim Joong-Hyun, Kim Tae-Hyun, Kim Hae-Won
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea; Department of Nanobiomedical Science and BK21 Plus NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, South Korea.
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea; Department of Nanobiomedical Science and BK21 Plus NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, South Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, South Korea.
PLoS One. 2014 Apr 4;9(4):e91584. doi: 10.1371/journal.pone.0091584. eCollection 2014.
Magnetic nanofibrous scaffolds of poly(caprolactone) (PCL) incorporating magnetic nanoparticles (MNP) were produced, and their effects on physico-chemical, mechanical and biological properties were extensively addressed to find efficacy for bone regeneration purpose. MNPs 12 nm in diameter were citrated and evenly distributed in PCL solutions up to 20% and then were electrospun into nonwoven nanofibrous webs. Incorporation of MNPs greatly improved the hydrophilicity of the nanofibers. Tensile mechanical properties of the nanofibers (tensile strength, yield strength, elastic modulus and elongation) were significantly enhanced with the addition of MNPs up to 15%. In particular, the tensile strength increase was as high as ∼25 MPa at 15% MNPs vs. ∼10 MPa in pure PCL. PCL-MNP nanofibers exhibited magnetic behaviors, with a high saturation point and hysteresis loop area, which increased gradually with MNP content. The incorporation of MNPs substantially increased the degradation of the nanofibers, with a weight loss of ∼20% in pure PCL, ∼45% in 10% MNPs and ∼60% in 20% MNPs. Apatite forming ability of the nanofibers tested in vitro in simulated body fluid confirmed the substantial improvement gained by the addition of MNPs. Osteoblastic cells favored the MNPs-incorporated nanofibers with significantly improved initial cell adhesion and subsequent penetration through the nanofibers, compared to pure PCL. Alkaline phosphatase activity and expression of genes associated with bone (collagen I, osteopontin and bone sialoprotein) were significantly up-regulated in cells cultured on PCL-MNP nanofibers than those on pure PCL. PCL-MNP nanofibers subcutaneously implanted in rats exhibited minimal adverse tissue reactions, while inducing substantial neoblood vessel formation, which however, greatly limited in pure PCL. In vivo study in radial segmental defects also signified the bone regeneration ability of the PCL-MNP nanofibrous scaffolds. The magnetic, bone-bioactive, mechanical, cellular and tissue attributes of MNP-incorporated PCL nanofibers make them promising candidate scaffolds for bone regeneration.
制备了含有磁性纳米颗粒(MNP)的聚己内酯(PCL)磁性纳米纤维支架,并广泛研究了其对物理化学、机械和生物学性能的影响,以寻找其在骨再生方面的功效。直径为12nm的MNP经过柠檬酸盐处理,并以高达20%的比例均匀分布在PCL溶液中,然后通过电纺丝制成非织造纳米纤维网。MNP的加入极大地提高了纳米纤维的亲水性。随着MNP添加量高达15%,纳米纤维的拉伸机械性能(拉伸强度、屈服强度、弹性模量和伸长率)显著增强。特别是,在15%的MNP含量下,拉伸强度增加高达约25MPa,而纯PCL中约为10MPa。PCL-MNP纳米纤维表现出磁行为,具有高饱和点和磁滞回线面积,且随着MNP含量的增加而逐渐增大。MNP的加入显著增加了纳米纤维的降解,纯PCL的重量损失约为20%,10%MNP的约为45%,20%MNP的约为60%。在模拟体液中体外测试的纳米纤维的磷灰石形成能力证实了添加MNP后获得的显著改善。与纯PCL相比,成骨细胞更倾向于含有MNP的纳米纤维,其初始细胞粘附和随后穿过纳米纤维的能力显著提高。在PCL-MNP纳米纤维上培养的细胞中,碱性磷酸酶活性和与骨相关的基因(I型胶原蛋白、骨桥蛋白和骨唾液蛋白)的表达明显高于纯PCL上培养的细胞。皮下植入大鼠的PCL-MNP纳米纤维表现出最小的不良组织反应,同时诱导大量新血管形成,而纯PCL中则大大受限。在桡骨节段性缺损的体内研究也表明了PCL-MNP纳米纤维支架的骨再生能力。含有MNP的PCL纳米纤维的磁性、骨生物活性、机械、细胞和组织特性使其成为骨再生的有前途的候选支架。