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Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation

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收录情况： ◇ SCIE

作者：
Wei Zhenyuan[1,2,3] * ; Ye Han[5] * ; Li Yucai[1,2,3] * ; Li Xiaoxiao[1,2,4] ; Liu Yi[1,2,3] ; Chen Yujie[1,2,4] ; Yu Jiangming[1,2,3,*1] ; Wang Jielin[1,2,4,*1] ; Ye Xiaojian[1,2,3,*1] ;
机构： [1]Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [2]Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai 200336, China [3]Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [4]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [5]Department of Ophthalmology and Vision Science, Shanghai Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai 20 0 031, China
出处：
DOI： 10.1016/j.actbio.2024.02.020
ISSN：

关键词： Annulus fibrosus Cell recruitment Repair Collagen mimetic peptide Microenvironment regulation

摘要：
Annulus fibrosus (AF) defect is an important cause of disc re-herniation after discectomy. The self-regeneration ability of the AF is limited, and AF repair is always hindered by the inflammatory microenvironment after injury. Hydrogels represent one of the most promising materials for AF tissue engineering strategies. However, currently available commercial hydrogels cannot withstand the harsh mechanical load within intervertebral disc. In the present study, an innovative triple cross-linked oxidized hyaluronic acid (OHA)-dopamine (DA)- polyacrylamide (PAM) composite hydrogel, modified with collagen mimetic peptide (CMP) and supplied with transforming growth factor beta 1 (TGF-β1) (OHA-DA-PAM/CMP/TGF-β1 hydrogel) was developed for AF regeneration. The hydrogel exhibited robust mechanical strength, strong bioadhesion, and significant self-healing capabilities. Modified with collagen mimetic peptide, the hydrogel exhibited extracellular-matrix-mimicking properties and sustained the AF cell phenotype. The sustained release of TGF-β1 from the hydrogel was pivotal in recruiting AF cells and promoting extracellular matrix production. Furthermore, the composite hydrogel attenuated LPS-induced inflammatory response and promote ECM synthesis in AF cells via suppressing NFκB/NLRP3 pathway. In vivo, the composite hydrogel successfully sealed AF defects and alleviated intervertebral disk degeneration in a rat tail AF defect model. Histological evaluation showed that the hydrogel integrated well with host tissue and facilitated AF repair. The strategy of recruiting endogenous cells and providing an extracellular-matrix-mimicking and anti-inflammatory microenvironment using the mechanically tough composite OHA-DA-PAM/CMP/TGF-β1 hydrogel may be applicable for AF defect repair in the clinic. STATEMENT OF SIGNIFICANCE: Annulus fibrosus (AF) repair is challenging due to its limited self-regenerative capacity and post-injury inflammation. In this study, a mechanically tough and highly bioadhesive triple cross-linked composite hydrogel, modified with collagen mimetic peptide (CMP) and supplemented with transforming growth factor beta 1 (TGF-β1), was developed to facilitate AF regeneration. The sustained release of TGF-β1 enhanced AF cell recruitment, while both TGF-β1 and CMP could modulate the microenvironment to promote AF cell proliferation and ECM synthesis. In vivo, this composite hydrogel effectively promoted the AF repair and mitigated the intervertebral disc degeneration. This research indicates the clinical potential of the OHA-DA-PAM/CMP/TGF-β1 composite hydrogel for repairing AF defects.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

基金：
This work was supported by grants from the Interdisciplinary Program of Shanghai Jiao Tong University (Grant No. YG2021ZD34, YG2022ZD030), the Funding of minimally invasive spine surgery research center of Shanghai Jiao Tong university (2021JCPT03), Lab- oratory Open Fund of Key Technology and Materials in Minimally Invasive Spine Surgery (2024JZWC-YBA06), Tongren Hospital Intro- duces the Talented Person Scientific Research Start Funds Subsi- dization Project (TR2022rc07) and Tongren Hospital Top Priority Subject Project (tr2023xk01)
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 1 区 工程：生物医学 1 区 材料科学：生物材料
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 工程：生物医学 1 区 材料科学：生物材料
JCR分区：
出版当年[2022]版：
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS
最新[2023]版：
Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [2]Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai 200336, China [3]Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
共同第一作者：
通讯作者：
通讯机构： [1]Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [2]Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai 200336, China [3]Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [4]Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China [*1]Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Wei Zhenyuan,Ye Han,Li Yucai,et al.Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation[J].ACTA BIOMATERIALIA.2024,178:50-67.doi:10.1016/j.actbio.2024.02.020.
APA：
Wei Zhenyuan,Ye Han,Li Yucai,Li Xiaoxiao,Liu Yi...&Ye Xiaojian.(2024).Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation.ACTA BIOMATERIALIA,178,
MLA：
Wei Zhenyuan,et al."Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation".ACTA BIOMATERIALIA 178.(2024):50-67

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