Ding Aixiang, Lee Sang Jin, Ayyagari Sriramya, Tang Rui, Huynh Cong Truc, Alsberg Eben
Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, 909 S. Wolcott Ave., Chicago, IL, 60612, USA.
Departments of Mechanical & Industrial Engineering, Orthopaedics, and Pharmacology, University of Illinois at Chicago, 909 S. Wolcott Ave., Chicago, IL, 60612, USA.
Bioact Mater. 2021 Jun 5;7:324-332. doi: 10.1016/j.bioactmat.2021.05.021. eCollection 2022 Jan.
Formation of graded biomaterials to render shape-morphing scaffolds for 4D biofabrication holds great promise in fabrication of complex structures and the recapitulation of critical dynamics for tissue/organ regeneration. Here we describe a facile generation of an adjustable and robust gradient using a single- or multi-material one-step fabrication strategy for 4D biofabrication. By simply photocrosslinking a mixed solution of a photocrosslinkable polymer macromer, photoinitiator (PI), UV absorber and live cells, a cell-laden gradient hydrogel with pre-programmable deformation can be generated. Gradient formation was demonstrated in various polymers including poly(ethylene glycol) (PEG), alginate, and gelatin derivatives using various UV absorbers that present overlap in UV spectrum with that of the PI UV absorbance spectrum. Moreover, this simple and effective method was used as a universal platform to integrate with other hydrogel-engineering techniques such as photomask-aided microfabrication, photo-patterning, ion-transfer printing, and 3D bioprinting to fabricate more advanced cell-laden scaffold structures. Lastly, proof-of-concept 4D tissue engineering was demonstrated in a study of 4D bone-like tissue formation. The strategy's simplicity along with its versatility paves a new way in solving the hurdle of achieving temporal shape changes in cell-laden single-component hydrogel scaffolds and may expedite the development of 4D biofabricated constructs for biological applications.
制备渐变生物材料以制造用于4D生物制造的形状变形支架，在制造复杂结构以及重现组织/器官再生的关键动态过程方面具有巨大潜力。在此，我们描述了一种使用单材料或多材料一步制造策略进行4D生物制造的简便方法，可生成可调节且稳定的梯度。通过简单地对可光交联聚合物大分子单体、光引发剂（PI）、紫外线吸收剂和活细胞的混合溶液进行光交联，即可生成具有预编程变形的载细胞梯度水凝胶。使用与PI紫外线吸收光谱在紫外线光谱上有重叠的各种紫外线吸收剂，在包括聚乙二醇（PEG）、藻酸盐和明胶衍生物在内的各种聚合物中证明了梯度的形成。此外，这种简单有效的方法被用作一个通用平台，与其他水凝胶工程技术如光掩模辅助微制造、光图案化、离子转移印刷和3D生物打印相结合，以制造更先进的载细胞支架结构。最后，在一项关于4D类骨组织形成的研究中展示了概念验证的4D组织工程。该策略的简单性及其多功能性为解决载细胞单组分水凝胶支架中实现时间形状变化的障碍开辟了一条新途径，并可能加速用于生物应用的4D生物制造构建体的开发。
