3D Bioprinting of Heterogeneous Constructs Providing Tissue‐Specific Microenvironment Based on Host–Guest Modulated Dynamic Hydrogel Bioink for Osteochondral Regeneration
Wenli Dai, Liwen Zhang, Yingjie Yu, Wenqiang Yan, Fenyuan Zhao, Yifei Fan, Chenxi Cao, Qing Cai, Xiaoqing Hu, Yingfang Ao
Abstract
Abstract 3D bioprinting is a promising strategy to develop heterogeneous constructs that mimic osteochondral tissue. However, conventional bioprinted hydrogels suffer from intrinsically weak mechanical strength, limited cell adaptability, and no sustained release of biochemical drugs, restraining their use as bioinks to emulate native osteochondral extracellular matrix. Herein, a novel host–guest modulated dynamic hydrogel is developed for 3D bioprinting heterogeneous cell‐laden constructs for osteochondral regeneration. Apart from gelatin methacryloyl (GelMA), this bioink consists of dopamine‐functionalized GelMA and acrylate β‐cyclodextrin and is crosslinked by host–guest interaction to develop the dynamic network for obtaining promoted cell adaptability, enhanced cell adhesion, reinforced mechanical strength, and tunable modulus. Moreover, based on the sustained drug release provided by the cavity of β‐cyclodextrin, a heterogeneous construct is constructed by employing kartogenin (a chondrogenic factor) into the upper zone with lower Young's modulus and melatonin (an osteogenic factor) into the bottom zone with higher modulus to mimic the osteochondral microenvironment. With the favorable regeneration results in vitro and in vivo, a broad application of this bioink in 3D bioprinting for tissues engineering is expected.