Transplantation of active nucleus pulposus cells with a keep-charging hydrogel microsphere system to rescue intervertebral disc degeneration

作者：Yingchuang Tang, Kai Zhang, Hongyou Zhou, Chenchen Zhang, Zixiang Liu, Hao Chen, Hanwen Li, Kangwu Chen · 发表于：Journal of Nanobiotechnology · 年份：2023 · DOI：10.1186/s12951-023-02226-1 · 被引用次数：33 · 研究领域：Spine and Intervertebral Disc Pathology、Tendon Structure and Treatment、Cervical and Thoracic Myelopathy

Abstract Background Cell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive. Methods In this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg 2+ to histidine-functionalized hyaluronic acid (HA-His-Mg 2+ ) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg 2+ , GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model. Results The GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg 2+ in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPC...