Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design  

作　　者：Juehan Wang Yulin Jiang Ce Zhu Zheng Liu Lin Qi Hong Ding Jing Wang Yong Huang Yubao Li Yueming Song Ganjun Feng Li Zhang Limin Liu 

机构地区：[1]Analytical&Testing Center,Department of Orthopedic Surgery and Orthopedic Research Institute,West China Hospital,Sichuan University,Chengdu,610065,China

出　　处：《Bioactive Materials》2024年第10期1-18,共18页生物活性材料（英文）

基　　金：the National Natural Science Foundation of China(82172495,82260431,82072434,82372453);Project funded by China Postdoctoral Science Foundation(2023M732469);Sichuan University Postdoctoral Interdisciplinary Innovation Fund(JCXK2205);Projects of the Science and Technology Department of Sichuan Province(2022ZDZX0029,MZGC20230019);the 1⋅3⋅5 project for disciplines of excellence Clinical Research Incubation Project,West China Hospital,Sichuan University(2021HXFH003).

摘　　要：Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)decline.Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline.Additionally,re-energizing the mitochondria damaged in the inflammatory milieu to restore their function,is equally important.Herein,we proposed an interesting concept of mitochondrion-engine equipped with coolant,which enables first to“cool-down”the inflammatory environment,next to restore the MMP,finally to allow cells to regain normal energy metabolism through materials design.As such,we developed a multifunctional composite composed of a reactive oxygen species(ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane(TPU)scaffold.The TPU scaffold was coated with conductive polypyrrole(PPy)to electrophoretically deposit L-arginine,which could upregulate the Mammalian target of rapamycin(mTOR)pathway,thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair.While the ROS-responsive hydrogel acting as the“mito-engine coolant”could scavenge the excessive ROS to create a favorable environment for IVD cells recovery.Demonstrated by in vitro and in vivo evaluations,the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress.Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair.This unique bioinspired design integrated biomaterial science with mitochondrial biology,presents a promising paradigm for IDD treatment.

关 键 词：Mitochondrial dysfunction Intervertebral disc degeneration L-ARGININE ROS scavenging Polyurethan scaffold 

分 类 号：R681.5[医药卫生—骨科学]