Swelling compensation of engineered vasculature fabricated by additive manufacturing and sacrifice-based technique using thermoresponsive hydrogel

Xue Yang; Shuai Li; Xin Sun; Ya Ren; Lei Qiang; Yihao Liu; Jinwu Wang; Kerong Dai

doi:10.18063/ijb.749

Swelling compensation of engineered vasculature fabricated by additive manufacturing and sacrifice-based technique using thermoresponsive hydrogel

Int J Bioprint. 2023 May 10;9(5):749. doi: 10.18063/ijb.749. eCollection 2023.

Authors

Xue Yang¹, Shuai Li², Xin Sun³, Ya Ren¹, Lei Qiang⁴, Yihao Liu³, Jinwu Wang^{3

5}, Kerong Dai^{1

3}

Affiliations

¹ College of Medicine, Southwest Jiaotong University, No. 144 Jiaoda Road, Chengdu 610031, People's Republic of China.
² Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Rd, Hangzhou 310003, People's Republic of China.
³ Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Rd, Shanghai 200011, People's Republic of China.
⁴ School of Materials Science and Engineering, Southwest Jiaotong University, No. 111 2nd Ring Rd, Chengdu 611756, People's Republic of China.
⁵ Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, No. 1956 Huashan Rd, Shanghai 200030, People's Republic of China.

Abstract

Engineered vasculature is widely employed to maintain the cell viability within in vitro tissues. A variety of fabrication techniques for engineered vasculature have been explored, with combination of additive manufacturing with a sacrifice-based technique being the most common approach. However, the size deformation of vasculature caused by the swelling of sacrificial materials remains unaddressed. In this study, Pluronic F-127 (PF-127), the most widely used sacrificial material, was employed to study the deformation of the vasculature. Then, a thermoresponsive hydrogel comprising poly(N-isopropylacrylamide) (PNIPAM) and gelatin methacrylate (GelMA) was used to induce volume shrinkage at 37°C to compensate for the deformation of vasculature caused by the swelling of a three-dimensional (3D)-printed sacrificial template, and to generate vasculature of a smaller size than that after deformation. Our results showed that the vasculature diameter increased after the sacrificial template was removed, whereas it decreased to the designed diameter after the volume shrinkage. Human umbilical vein endothelial cells (HUVECs) formed an endothelial monolayer in the engineered vasculature. Osteosarcoma cells (OCs) were loaded into a hierarchical vasculature within the thermoresponsive hydrogel to investigate the interaction between HUVECs and OCs. New blood vessel infiltration was observed within the lumen of the engineered vasculature after in vivo subcutaneous implantation for 4 weeks. In addition, engineered vasculature was implanted in a rat ischemia model to further study the function of engineered vasculature for blood vessel infiltration. This study presents a small method aiming to accurately create engineered vasculature by additive manufacturing and a sacrificebased technique.

Keywords: Additive manufacturing; Engineered vasculatures; Sacrificial materials; Swelling compensation; Thermoresponsive hydrogels.