An injectable anti-vascularization functionalized hydrogel for degenerative nucleus pulposus repair  

作　　者：Hao Hu Rongcheng Hu Xihong Fu Yibo Wang Yuan Zhang Shuai Chen Tingxuan Wang Shangbin Cui Yong Wan Wei Guo Xuenong Zou Chun Liu 

机构地区：[1]Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology,Department of Spinal Surgery/The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China [2]Institute of Precision Medicine,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China

出　　处：《Journal of Materials Science & Technology》2024年第36期143-154,共12页材料科学技术(英文版)

基　　金：supported in part by the National Natural Science Foundation of China(No.32101062);the Guangdong Basic and Applied Basic Re-search Foundation(No.2022A1515012607);the National Natural Science Foundation of China(No.82202741);the Chinese Postdoc-toral Science Foundation(No.2021M703710);the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515111040);the Guangzhou Science and Technology Projects-Major R&D Program(No.2023B03J1386);the National Natural Science Foundation of China(General Program)(No.32071341).

摘　　要：Neovascularization and inflammatory cell invasion within the nucleus pulposus(NP)constitute pivotal pathological changes during the acceleration stage of intervertebral disc degeneration(IDD).Mesenchy-mal stem cells(MSCs),renowned for their remarkable capacity in intervertebral disc(IVD)regeneration,also exhibit the capability to secrete pro-angiogenic factors,expediting IDD progression under hypoxic conditions.Consequently,we developed a hydrogel comprised of methacrylated hyaluronic acid(HAMA),rat tail collagen I(COL),and MSCs,incorporating the vascular endothelial growth factor receptor(VEGFR)inhibitor cabozantinib(Cabo@HAMA-COL/MSCs hydrogel).This innovative construct aimed to facilitate NP regeneration while mitigating vascularization and inflammation.Our findings revealed that the hydrogel aptly mimicked the mechanical characteristics of NP tissue,exhibiting injectability,low cytotoxicity,and the preservation of the cellular phenotype of NP cells.Co-culturing of MSCs and human umbilical vein endothelial cells(HUVECs)promoted migration,tube formation,and sprouting of HUVECs,which will be inhibited by cabozantinib.In vivo experiments demonstrated that Cabo@HAMA-COL/MSCs hydrogel main-tained disc height,protected NP,and alleviated vascularization and inflammation in a puncture-induced rat caudal IDD model.Consequently,our results substantiate that Cabo@HAMA-COL/MSCs hydrogel can prevent IDD degeneration by ameliorating the vascularization-inflammation pathological microenviron-ment,offering a promising therapeutic strategy for IDD.

关 键 词：Nucleus pulposus regeneration HYDROGEL Cabozantinib Anti-vascularization Pathological microenvironment 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]