Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University,1954 Huashan Road, Shanghai 200030, China.
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University,1954 Huashan Road, Shanghai 200030, China.
Colloids Surf B Biointerfaces. 2017 Dec 1;160:500-509. doi: 10.1016/j.colsurfb.2017.10.002. Epub 2017 Oct 3.
It has been widely accepted that cell behaviors can be affected by multiple kinds of biomaterial stimulation signals. Although many literatures have focused on studying the multiple biomaterials stimulatory cues in affecting cellular behaviors, systematic studies on the effects of individual and combination of multiple biomaterials stimulatory cues in regulating cellular behaviors and their potential possible mechanisms have rarely been reported. We hypothesized that tissue engineering scaffolds with enhanced bioactivity can be designed if synergetic effects between different kinds of biomaterial stimulation cues in affecting cells behaviors can be found and applied. To prove our concept, in this study, electrospun nanofibers were used to provide structure cues and bioactive glass (BG) ion extracts were used to provide chemistry cues. The effects of single type of electrospun nanofiber structure cues, single type of BG chemical cues and combined application of the two types of stimulatory cues on behaviors of human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) were evaluated. Results showed that the nanostructure cues of electrospun nanofibers mainly affected cell morphology and cytoskeleton distribution while the chemistry cues of BG ion extracts played important roles in promoting cell proliferation. Both of the electrospun nanofiber structure and BG chemistry cues contributed to cell differentiation, including extracellular matrix synthesis of HDFs and vascularization of HUVECs. Interestingly, when the two kinds of stimulatory cues were applied together, obvious synergetic effects were observed as the combination of the two stimulatory cues showed the strongest stimulation effects on cell differentiation among all groups. Taken together, it is feasible to simultaneously apply two or more kinds of biomaterial stimulation signals to synergistically affect cell behaviors and enhance tissue regeneration, which is critical for instructing the design of tissue engineering scaffolds or biomaterial substrates with improved bioactivity.
人们普遍认为，细胞行为可以受到多种生物材料刺激信号的影响。虽然许多文献都集中在研究多种生物材料刺激线索对细胞行为的影响，但系统研究单一和多种生物材料刺激线索在调节细胞行为及其潜在机制方面的协同作用的文献却很少。我们假设，如果能够发现并应用不同种类生物材料刺激线索在影响细胞行为方面的协同作用，就可以设计出具有增强生物活性的组织工程支架。为了验证我们的概念，在这项研究中，我们使用静电纺纳米纤维提供结构线索，使用生物活性玻璃（BG）离子提取物提供化学线索。评估了单一类型静电纺纳米纤维结构线索、单一类型 BG 化学线索以及这两种刺激线索的组合应用对人真皮成纤维细胞（HDFs）和人脐静脉内皮细胞（HUVECs）行为的影响。结果表明，静电纺纳米纤维的纳米结构线索主要影响细胞形态和细胞骨架分布，而 BG 离子提取物的化学线索在促进细胞增殖方面起着重要作用。静电纺纳米纤维的结构和 BG 化学线索都有助于细胞分化，包括 HDFs 的细胞外基质合成和 HUVECs 的血管生成。有趣的是，当两种刺激线索一起应用时，观察到明显的协同作用，因为两种刺激线索的组合在所有组中对细胞分化表现出最强的刺激作用。总之，同时应用两种或多种生物材料刺激信号以协同影响细胞行为并增强组织再生是可行的，这对于指导组织工程支架或生物材料基底的设计具有重要意义，以提高其生物活性。
