PU/液晶复合材料3D打印力学传导型组织工程支架及其细胞力学响应

The composition, preparation methods, modification, biological evaluation and the clinical application of tissue engineering scaffolds are changing with each passing day. How to make scaffolds fully respond to changes in the biological microenvironment and transmit the biomechanical signals to cells has not yet been fundamentally resolved, especially for cells inside the scaffold. The key scientific question is the elastic modulus of the scaffold does not match the microenvironment. This project is based on the long-term studies of polymer/ liquid crystal composite films. In this project a kind of elastic modules adjustable and biodegradable polyether polyurethane was used as scaffold material. Its cholesterol derivatives have liquid-crystal transformation properties and biocompatibility. By 3D printing technology they can be prepared as new tissue engineering scaffolds which have the adjustable elastic modulus and ability to transmit the microenvironment biomechanical signals to cells. The influence of the force type, material composite, scaffold structure and other factors on the mechanical properties of the scaffold will be deeply investigated. The mechanics attenuation of the scaffold during the degradation will be studied. In addition the effect of mechanical environment on the growth, proliferation and function of cells inside the scaffold will be investigated by using biomechanics reactor. This project will build the theoretical foundation and technical solutions for developing a new mechanical conductible tissue engineering scaffold.

组织工程支架的材料组成，制备方法，复合修饰，生物学评价、临床使用技术的研究日新月异，但如何使支架材料完全响应生物微环境的变化并转导致细胞的响应，尤其是支架内部细胞对力学环境的响应及其对细胞功能的影响至今尚未从根本上解决，其关键的科学问题是支架材料的弹性模量不匹配所致。本项目是在长期聚合物/液晶复合膜生物相容性研究的基础上，利用弹性模量可调的可降解聚醚聚氨酯作为基质材料，利用胆甾醇衍生物液晶的有序流动性能及其良好的细胞相容性，借助三维（3D）打印技术制备一种弹性模量可调并可传导微环境生物力学刺激的新型组织工程支架。在系统研究微重力、压缩力和剪切力作用下，不同组成，不同孔径、孔隙率的支架形变规律及其对细胞影响的基础上，基本探明支架降解过程中的力学衰减规律。借助生物反应器深入探讨各种力学环境对支架内部细胞生长、增殖和功能的影响，为开发一种力学传导型组织工程支架奠定理论基础和技术。

本项目在长期聚合物/液晶复合膜生物相容性研究的基础上，以弹性模量可调的可降解聚酯作为基质材料，利用胆甾醇衍生物液晶的有序流动性能及其良好的细胞相容性，借助三维（3D）打印技术制备一种弹性模量可调并可传导微环境生物力学刺激的新型组织工程支架。通过氯化反应和硅氢加成反应合成了六种基于具有侧链胆固醇基的脂肪族聚碳酸酯单体液晶和四种弹性体聚合物液晶。通过三维打印成型技术构建了PU/LC三维复合支架，探讨了支架的抗压强度，孔隙率，亲水性和细胞相容性。复合支架具较高的机械强度，液晶的引入有利于提高材料表面的细胞亲和力，增加细胞粘附率和细胞活性，并且对hMSC的成骨分化具有特定的积极作用。在聚酯材料中负载DNA质粒，能够保持较高的质粒活性和转染效率，证明该类材料可以作为有效的质粒载体，构建具有促血管、成骨等多种活性的组织工程支架。3D打印能够有效地构建不同复杂结构，不同孔隙率的支架，通过支架的组成、立体结构、填充密度等能够调控所制备材料的力学性能、降解速率等特性。将双网络水凝胶作为细胞载体与聚酯材料共同打印，制备了负载干细胞的组织工程支架。在系统研究不同组成，不同孔径、孔隙率的支架形变规律及其对细胞影响的基础上，基本探明支架降解过程中的力学衰减规律，深入探讨各种力学环境对支架内部细胞生长、增殖和功能的影响，为开发一种力学传导型组织工程支架奠定了理论基础和实验基础。