Stiffness memory nanohybrid scaffolds generated by indirect 3D printing for biologically responsive soft implants.
Stiffness memory nanohybrid scaffolds generated by indirect 3D printing for biologically responsive soft implants.
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DOI：
10.1016/j.actbio.2018.09.016
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发表时间：
2018-10
影响因子：
9.7
通讯作者：
Linxiao Wu;J. Virdee;E. Maughan;A. Darbyshire;G. Jell;M. Loizidou;M. Emberton;P. Butler;A. Howkins;A. Reynolds;I. Boyd;M. Birchall;Wenhui Song
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作者：
Linxiao Wu;J. Virdee;E. Maughan;A. Darbyshire;G. Jell;M. Loizidou;M. Emberton;P. Butler;A. Howkins;A. Reynolds;I. Boyd;M. Birchall;Wenhui Song
细胞和组织的硬度是动态生物过程的一个重要的生物力学信号参数；因此，具有响应功能的响应性聚合物材料在活体植入物中具有吸引力。通过一种多功能的3D打印引导的热诱导相分离(3D-TIPS)技术，我们已经开发出具有‘刚性记忆’的热响应性聚(尿素-氨酯)纳米杂化支架。3D-TIPS是3D打印与相分离的结合，允许聚合物溶液在打印的牺牲预制件内的大网络界面上进行均匀的相分离和相变，从而创建具有定制解剖复杂几何形状的全尺寸支架。具有多尺度、可控制的孔隙率和结晶度的具有相互连接的孔的软弹性体支架已经被制造出广泛的超弹性力学性能，这是以前仅通过直接打印技术或相分离无法实现的。半结晶聚合物反向自组装为基态准随机纳米相结构，贯穿于内部孔的分级结构，有助于在体外细胞培养中以最小的形状变化逐渐松弛硬度。这种“刚性记忆”为周围组织提供最初的机械支持，然后逐渐软化到更好的机械匹配，这为个性化和生物响应性软组织植入物带来了希望，这种软组织植入物可以促进人类成纤维细胞的生长作为模型和潜在的支架组织整合。意义陈述生物过程本质上是动态的，但目前的医疗植入物往往比周围组织更坚固，对生物和物理刺激的反应几乎没有适应性。这项工作有助于开发一系列热响应性纳米杂化弹性体支架，具有可调节的硬度和分级互连的多孔结构，通过通用的间接3D打印技术制造。首次观察到支架的刚性记忆是由相变和从半晶相到准随机纳米橡胶相的反向自组装驱动的。在支架体外僵硬松弛过程中对细胞反应的早期洞察为个性化生物响应性软植入物提供了希望。
Cell and tissue stiffness is an important biomechanical signalling parameter for dynamic biological processes; responsive polymeric materials conferring responsive functionality are therefore appealing forin vivoimplants. We have developed thermoresponsive poly(urea-urethane) nanohybrid scaffolds with ‘stiffness memory’ through a versatile 3D printing-guided thermally induced phase separation (3D-TIPS) technique. 3D-TIPS, a combination of 3D printing with phase separation, allows uniform phase-separation and phase transition of the polymer solution at a large interface of network within the printed sacrificial preform, leading to the creation of full-scale scaffolds with bespoke anatomical complex geometry. A wide range of hyperelastic mechanical properties of the soft elastomer scaffolds with interconnected pores at multi-scale, controlled porosity and crystallinity have been manufactured, not previously achievable via direct printing techniques or phase-separation alone. Semi-crystalline polymeric reverse self-assembly to a ground-stated quasi-random nanophase structure, throughout a hierarchical structure of internal pores, contributes to gradual stiffness relaxation duringin vitrocell culture with minimal changes to shape. This ‘stiffness memory’ provides initial mechanical support to surrounding tissues before gradually softening to a better mechanical match, raising hopes for personalized and biologically responsive soft tissue implants which promote human fibroblast cells growth as model and potential scaffold tissue integration.Statement of SignificanceBiological processes are dynamic in nature, however current medical implants are often stronger and stiffer than the surrounding tissue, with little adaptability in response to biological and physical stimuli. This work has contributed to the development of a range of thermoresponsive nanohybrid elastomer scaffolds, with tuneable stiffness and hierarchically interconnected porous structure, manufactured by a versatile indirect 3D printing technique. For the first time, stiffness memory of the scaffold was observed to be driven by phase transition and a reverse self-assembly from a semicrystalline phase to a quasi-random nanostructured rubber phase. Early insight into cell response during the stiffness relaxation of the scaffoldsin vitroholds promise for personalized biologically responsive soft implants.