Department of Biomaterials, Radboud University Nijmegen Medical Center, 309 Dentistry, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Biomaterials. 2012 Oct;33(28):6604-14. doi: 10.1016/j.biomaterials.2012.06.018. Epub 2012 Jul 5.
The aim of current study was to evaluate the effect of nano-apatitic particles (nAp) incorporation on the degradation characteristics and biocompatibility of poly(lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds. Composite PLGA/poly(ɛ-caprolactone) (PCL) blended (w/w = 3/1) polymeric electrospun scaffolds with 0-30 wt% of nAp incorporation (n0-n30) were prepared. The obtained scaffolds were firstly evaluated by morphological, physical and chemical characterization, followed by an in vitro degradation study. Further, n0 and n30 in both virgin and 3-week pre-degraded status were subcutaneously implanted in rats, either directly or in stainless steel mesh cages, to evaluate in vivo tissue response. The results showed that the incorporation of nAp yields an nAp amount-dependent buffering effect on pH-levels during degradation and delayed polymer degradation based on molecular weight analysis. Regarding biocompatibility, nAp incorporation significantly improved the tissue response during a 4-week subcutaneous implantation, showing less infiltration of inflammatory cells (monocyte/macrophages) as well as less foreign body giant cells (FBGCs) formation surrounding the scaffolds. Similar cytokine expression (gene and protein level) was observed for all groups of implanted scaffolds, although marginal differences were found for TNF-α and TGF-β at gene level as well as GRO-KC at protein level after 1 week of implantation. The results of the current study indicate that hybridization of the weak alkaline salt nAp is effective to control the in vivo adverse tissue reaction of PLGA materials, which is beneficial for optimizing final clinical application of different PLGA-based biomedical devices.
本研究旨在评估纳米磷灰石颗粒(nAp)的掺入对聚(乳酸-共-乙醇酸)(PLGA)基纳米纤维支架降解特性和生物相容性的影响。制备了含有 0-30wt%nAp(n0-n30)的复合 PLGA/聚(己内酯)(PCL)共混(w/w=3/1)的聚合物电纺支架。首先对获得的支架进行形态学、物理和化学特性评价,然后进行体外降解研究。进一步将 virgin 和 3 周预降解状态下的 n0 和 n30 分别直接或置于不锈钢网笼中皮下植入大鼠,以评估体内组织反应。结果表明,nAp 的掺入对降解过程中的 pH 值具有 nAp 量依赖性的缓冲作用,并根据分子量分析延迟了聚合物的降解。关于生物相容性,nAp 的掺入在 4 周的皮下植入过程中显著改善了组织反应,表现为支架周围浸润的炎症细胞(单核细胞/巨噬细胞)和异物巨细胞(FBGCs)形成减少。所有植入支架组的细胞因子表达(基因和蛋白水平)相似,尽管在植入后 1 周,TNF-α 和 TGF-β 的基因水平以及 GRO-KC 的蛋白水平存在微小差异。本研究结果表明,弱碱性盐 nAp 的杂交可有效控制 PLGA 材料的体内不良组织反应,有利于优化不同 PLGA 基生物医学器件的最终临床应用。