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Four-dimensional printing hierarchy scaffolds with highly biocompatible smart polymers for tissue engineering applications

机译：具有高度生物相容性的智能聚合物的四维打印层次支架，用于组织工程应用

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The objective of this study was to four-dimensional (4D) print novel biomimetic gradient tissue scaffolds with highly biocompatible naturally derived smart polymers. The term "4D printing" refers to the inherent smart shape transformation of fabricated constructs when implanted minimally invasively for seamless and dynamic integration. For this purpose, a series of novel shape memory polymers with excellent biocompatibility and tunable shape changing effects were synthesized and cured in the presence of three-dimensional printed sacrificial molds, which were subsequently dissolved to create controllable and graded porosity within the scaffold. Surface morphology, thermal, mechanical, and biocompatible properties as well as shape memory effects of the synthesized smart polymers and resultant porous scaffolds were characterized. Fourier transform infrared spectroscopy and gel content analysis confirmed the formation of chemical crosslinking by reacting polycaprolactone triol and castor oil with multi-isocyanate groups. Differential scanning calorimetry revealed an adjustable glass transition temperature in a range from '8°C to 35°C. Uniaxial compression testing indicated that the obtained polymers, possessing a highly crosslinked interpenetrating polymeric networks, have similar compressive modulus to polycaprolactone. Shape memory tests revealed that the smart polymers display finely tunable recovery speed and exhibit greater than 92% shape fixing at '18°C or 0°C and full shape recovery at physiological temperature. Scanning electron microscopy analysis of fabricated scaffolds revealed a graded microporous structure, which mimics the nonuniform distribution of porosity found within natural tissues. With polycaprolactone serving as a control, human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and differentiation greatly increased on our novel smart polymers. The current work will significantly advance the future design and development of novel and functional biomedical scaffolds with advanced 4D printing technology and highly biocompatible smart biomaterials.
机译：这项研究的目的是要使用具有高度生物相容性的天然衍生的智能聚合物进行二维（4D）打印新型仿生梯度组织支架。术语“ 4D打印”是指当以微创方式植入以实现无缝和动态集成时，所构建结构的固有智能形状转换。为此，在具有三维印刷牺牲模子的情况下，合成并固化了一系列具有优异生物相容性和可调形状改变效果的新型形状记忆聚合物，随后将其溶解以在支架内产生可控且分级的孔隙率。表征了合成的智能聚合物和所得多孔支架的表面形态，热，机械和生物相容性以及形状记忆效应。傅里叶变换红外光谱和凝胶含量分析证实了聚己内酯三醇和蓖麻油与多异氰酸酯基团的反应形成了化学交联。差示扫描量热法显示可调节的玻璃化转变温度在'8℃至35℃的范围内。单轴压缩试验表明，所获得的具有高度交联的互穿聚合物网络的聚合物具有与聚己内酯相似的压缩模量。形状记忆测试表明，智能聚合物显示出微调的恢复速度，并在'18°C或0°C下显示出超过92％的形状固定，并在生理温度下显示出完全的形状恢复。制成的支架的扫描电子显微镜分析显示出渐变的微孔结构，该结构模仿了天然组织中发现的孔隙率的不均匀分布。以聚己内酯为对照，人类新型骨髓间质干细胞的粘附，增殖和分化在我们的新型智能聚合物上得到了极大的提高。当前的工作将极大地推动具有先进4D打印技术和高度生物相容性智能生物材料的新型功能性生物医学支架的未来设计和开发。

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