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(M...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.展开更多
Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic...Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials,which endangers the survival,proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants.If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level,it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue.In this review,we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress,then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress.And finally,we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair.The main content of this review is summarized in the following graphical abstract.展开更多
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)+4 种基金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).
文摘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.
基金financially supported by the National Nat-ural Science Foundation of China(Nos.32071341,82202741,52003302,31430030,51973021,32201111,and 52202358)the Chinese Postdoctoral Science Foundation(Nos.2021M703710 and 2021M691464)+1 种基金the Guangdong Basic and Applied Basic Re-search Foundation(Nos.2021A1515111040,2019A1515110841 and 2019A1515011935)the Beijing Municipal Health Commis-sion(Nos.BMHC-20216 and PXM 2020_026275_000002)。
文摘Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials,which endangers the survival,proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants.If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level,it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue.In this review,we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress,then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress.And finally,we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair.The main content of this review is summarized in the following graphical abstract.
