Rosellini Elisabetta, Barbani Niccoletta, Frati Caterina, Madeddu Denise, Massai Diana, Morbiducci Umberto, Lazzeri Luigi, Falco Angela, Lagrasta Costanza, Audenino Alberto, Cascone Maria Grazia, Quaini Federico
1 Department of Civil and Industrial Engineering, University of Pisa, Pisa, Italy.
2 Department of Medicine and Surgery, University of Parma, Parma, Italy.
J Appl Biomater Funct Mater. 2018 Oct;16(4):241-251. doi: 10.1177/2280800018782844. Epub 2018 Jul 5.
Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium. In particular, the effect of particle size on cardiac progenitor cell response was investigated.
Particles were produced by a water-in-oil emulsion method. Phosphatidylcholine was used as a surfactant. Particles with different diameter ranges (125-300 µm and 350-450 µm) were fabricated using two different surfactant concentrations. Morphological, physicochemical, and functional characterizations were carried out. Cardiac progenitor cell adhesion and growth on microparticles were tested both in static and dynamic suspension culture conditions.
Morphological analysis of the produced particles showed a spherical shape and porous surface. The hydrophilicity of particle matrix and the presence of intermolecular interactions between gellan and gelatin were pointed out by the physicochemical characterization. A weight loss of 75 ± 5 % after 90 days of hydrolytic degradation was observed. Injectability through a narrow needle (26 G) and persistence of the microparticles at the injection site were preliminarily verified by ex vivo test. In vitro cell culture tests showed a preservation of rat cardiac progenitor biologic properties and indicated a preferential cell adherence to microparticles with a smaller size.
Overall, the obtained results indicate that the produced gelatin/gellan microparticles could be potentially employed as injectable scaffolds for myocardial regeneration.
可注射支架正在成为心肌组织工程领域一种有前景的策略。在可注射支架中,对微粒的研究较少。本研究的目的是开发新型明胶/结冷胶微粒,其可作为可注射支架用于修复梗死心肌。特别地,研究了粒径对心脏祖细胞反应的影响。
通过油包水乳液法制备微粒。使用磷脂酰胆碱作为表面活性剂。使用两种不同的表面活性剂浓度制备了不同直径范围(125 - 300 µm和350 - 450 µm)的微粒。进行了形态学、物理化学和功能表征。在静态和动态悬浮培养条件下测试了心脏祖细胞在微粒上的黏附和生长情况。
所制备微粒的形态学分析显示为球形且表面多孔。物理化学表征指出了微粒基质的亲水性以及结冷胶和明胶之间分子间相互作用的存在。观察到水解降解90天后重量损失75±5%。通过体外试验初步验证了微粒可通过细针(26G)注射且在注射部位的持久性。体外细胞培养试验显示大鼠心脏祖细胞生物学特性得以保留,并表明细胞更倾向于黏附在较小尺寸的微粒上。
总体而言,所得结果表明所制备的明胶/结冷胶微粒有可能用作心肌再生的可注射支架。