Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native...Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.展开更多
Majority of cancer patients die from cancer metastases.The physical stimulation produced by microenvironment regulates invasive behavior of cancer cells.Blood vessel is one of the“pathways”for cancer to metastasize,...Majority of cancer patients die from cancer metastases.The physical stimulation produced by microenvironment regulates invasive behavior of cancer cells.Blood vessel is one of the“pathways”for cancer to metastasize,in which tumor cells need to cross the endothelial barrier for intravasation and extravasation.Tumor vessels are arranged in untraditional hierarchies and characterized with rupture,bend,swell and high permeability that are beneficial to intravasation of cancer cell.Abnormal vessels are accompanied with uneven blood flow,increased compression and interstitial fluid pressure.Meanwhile,excessive proliferation of tumor leads to low oxygen pressure in solid tumor.The aberrant tumor mechanical microenvironment changes the biochemical and mechanical signal transduction of endothelial cells and participates in tumor progression.Many current researches focus on how chemical signals regulate endothelial cell function while the role of physical cues is unclear.In this review,the role of endothelial cells in the regulation of shear stress,intercellular force,extracellular matrix and pressure on tumor progression is summarized.展开更多
Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytos...Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.展开更多
Mechanical microenvironment can strongly affect the metastatic efficiency of circulating tumor cells.However,the effect of suspension state on their extravasation and the mechanisms involved are still unclear.To explo...Mechanical microenvironment can strongly affect the metastatic efficiency of circulating tumor cells.However,the effect of suspension state on their extravasation and the mechanisms involved are still unclear.To explore the influence of suspension state on extravasation(including adhesion,spreading and transendothelial migration)of breast tumor cells and its relevant molecular mechanism,MDA-MB-231 cells were cultured on poly(2-hydroxyethyl methacrylate)coated 6-well plates to minic the suspension state.Suspension state promoted adhesion,spreading and transendothelial migration of MDA-MB-231 cells to EAhy926 endothelial cells(ECs)monolayer under both the static condition and 0.5 dyne/cm^(2) flow shear stress(FSS).The number of cells adhered to ECs monolayer reached 2.15(static condition,3 d)and 1.67(FSS,3 d)times,and the number of migration reached 10.60 times,respectively,as compared to that in adhesion state.Moreover,MDA-MB-231 cells knockdown of integrin β1 provoked poor adhesion and transendothelial migration,as compared with MDA-MB-231 cells.But it made no difference in cell spreading.Our results implied the increasing expression of integrin β1 induced by suspension culture promoted the adhesion and transendothelial migration of MDA-MB-231 cells,but had no significant influence on their spreading.展开更多
Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-ta...Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-targeting nanomedicine by conjugating doxorubicin(DOX)-loaded hydroxyethyl starch-IR780 nanoparticles(NPs)with Cys-Arg-Glu-Lys-Ala(CREKA)peptide,which had a special affinity for fibronectin overexpressed on CAFs.After systemic administration,the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation,decreasing CAFs through the combination of chemo-and photothermal-therapies.Thus,a series of changes in TMME were achieved by reducing CAFs,which further disrupted the niche of cancer stem cells(CSCs)to affect their survival.As a result,the tumor growth was significantly inhibited in 4T1 tumors.The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors.展开更多
Periodontitis can cause irreversible defects in the periodontal ligament(PDL),the regeneration of which is the major obstacle to the clinical treatment of periodontitis.Implanting hydrogel for releasing anti-inflammat...Periodontitis can cause irreversible defects in the periodontal ligament(PDL),the regeneration of which is the major obstacle to the clinical treatment of periodontitis.Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration.However,existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium,which may have been shown as an important role in tissue regeneration.Meanwhile,the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive.In this study,we developed a bi-crosslinking viscoelastic hydrogel(Alg-PBA/Spd)by integrating phenylboronic acid-modified alginate with anti-inflammatory agent(spermidine)through borate ester and B-N coordination bonds,where spermidine will be released with the degradation of the hydrogel.Alg-PBA/Spd hydrogel is biocompatible,injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking.We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage.Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.展开更多
基金support of the National Key Research and Development Program of China(2016YFE0132700)National Natural Science Foundation of China(51822306,51673171)+1 种基金Science Technology Department of Zhejiang Province(2020C03042)the Fundamental Research Funds for the Central Universities of China.
文摘Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix.These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility.It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues.Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix.The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows.First,we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry.Next,we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate,including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling.Finally,we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine.We conclude by discussing the limitations and challenges for adaptable hydrogel,and we present perspectives for future studies.
基金This work was supported in part by the National Natural Science Foundation of China(Grants Nos.11872134 and 12072054)the Natural Science Foundation of Chongqing,China(Grant cstc2020jcyj-msxmX0035).
文摘Majority of cancer patients die from cancer metastases.The physical stimulation produced by microenvironment regulates invasive behavior of cancer cells.Blood vessel is one of the“pathways”for cancer to metastasize,in which tumor cells need to cross the endothelial barrier for intravasation and extravasation.Tumor vessels are arranged in untraditional hierarchies and characterized with rupture,bend,swell and high permeability that are beneficial to intravasation of cancer cell.Abnormal vessels are accompanied with uneven blood flow,increased compression and interstitial fluid pressure.Meanwhile,excessive proliferation of tumor leads to low oxygen pressure in solid tumor.The aberrant tumor mechanical microenvironment changes the biochemical and mechanical signal transduction of endothelial cells and participates in tumor progression.Many current researches focus on how chemical signals regulate endothelial cell function while the role of physical cues is unclear.In this review,the role of endothelial cells in the regulation of shear stress,intercellular force,extracellular matrix and pressure on tumor progression is summarized.
基金funded by"Beijing Natural Science Foundation,grant number 6224060","Young Elite Scientists Sponsorship Program by BAST,grant number",BYESS2023192"Program of Beijing Municipal Education Commission,grant number KM202310020006"+1 种基金"Bejing University of Agriculture science and Technology innovation Sparkling support plan,grant number,BUA-HHXD2022007""2022 Research and Innovation ability improvement plan for young teachers of Beijing University of Agriculture,grant number QJKC2022028".
文摘Anticancer drugs are one of the most direct means of cancer therapy.However,the various cancer progressions hamper the development and discovery of anticancer drugs.In fact,the mechanical properties of the tumor cytoskeleton are extremely vital for any phase of cancer,especially in tumor invasion and metastasis.However,in the current category of anticancer drugs,the cytoskeleton-targeting drugs are limited and their role in tumor progression is unclear.Here,we present the mechanical characteristics of tumor stiffness that are tightly regulated by the cancer cytoskeleton,including actin filaments and microtubules during tumor initiation,growth and metastasis,and review the natural drugs that target the cancer cytoskeleton.We define cytoskeleton dynamics as target mechanisms for anticancer drugs and summarize the plant,microbial and marine sources of natural products.Furthermore,this paper also provides a material pathway to study active tumor mechanics,and introduces the unique advantages and future application potential of tumor cytoskeleton-targeting drugs in clinical use.The material approaches to active cancer mechanics are supplied in this review.We aim to promote the development of anticancer drugs that target tumor mechanics by using those material approaches and finding their pharmacological application.
基金supported in part by grants from the National Natural Science Foundation of China(11672051)Fundamental Research Funds for the Central Universities(2018CDQYSG0015).
文摘Mechanical microenvironment can strongly affect the metastatic efficiency of circulating tumor cells.However,the effect of suspension state on their extravasation and the mechanisms involved are still unclear.To explore the influence of suspension state on extravasation(including adhesion,spreading and transendothelial migration)of breast tumor cells and its relevant molecular mechanism,MDA-MB-231 cells were cultured on poly(2-hydroxyethyl methacrylate)coated 6-well plates to minic the suspension state.Suspension state promoted adhesion,spreading and transendothelial migration of MDA-MB-231 cells to EAhy926 endothelial cells(ECs)monolayer under both the static condition and 0.5 dyne/cm^(2) flow shear stress(FSS).The number of cells adhered to ECs monolayer reached 2.15(static condition,3 d)and 1.67(FSS,3 d)times,and the number of migration reached 10.60 times,respectively,as compared to that in adhesion state.Moreover,MDA-MB-231 cells knockdown of integrin β1 provoked poor adhesion and transendothelial migration,as compared with MDA-MB-231 cells.But it made no difference in cell spreading.Our results implied the increasing expression of integrin β1 induced by suspension culture promoted the adhesion and transendothelial migration of MDA-MB-231 cells,but had no significant influence on their spreading.
基金the National Research and Development Program of China(Nos.2018YFA0208900,2020YFA0211200,and 2020YFA0710700)the National Natural Science Foundation of China(Nos.82172757 and 31972927)+2 种基金the Scientific Research Foundation of Huazhong University of Science and Technology(No.3004170130)the Program for HUST Academic Frontier Youth Team(No.2018QYTD01)the HCP Program for HUST.
文摘Cancer-associated fibroblasts(CAFs)play an important role in facilitating the progression of triple-negative breast cancer(TNBC)by deteriorating the tumor mechanical microenvironment(TMME).Herein,we designed a CAFs-targeting nanomedicine by conjugating doxorubicin(DOX)-loaded hydroxyethyl starch-IR780 nanoparticles(NPs)with Cys-Arg-Glu-Lys-Ala(CREKA)peptide,which had a special affinity for fibronectin overexpressed on CAFs.After systemic administration,the NPs efficiently targeted CAFs and generated hyperthermia upon light irradiation,decreasing CAFs through the combination of chemo-and photothermal-therapies.Thus,a series of changes in TMME were achieved by reducing CAFs,which further disrupted the niche of cancer stem cells(CSCs)to affect their survival.As a result,the tumor growth was significantly inhibited in 4T1 tumors.The strategy of TMME modulation and CSCs elimination through targeting and depleting CAFs provides a novel therapeutic treatment for desmoplastic solid tumors.
基金supported by the National Natural Science Foundation of China(31971248,12225208 and 12002263)Science and Technology Innovation Team Project,Shaanxi Province(2021TD-46)the Young Talent Support Plan of Xi’an Jiaotong University,and supported by the Fundamental Research Funds for the Central Universities(xzy012020079,xzd012021037).
文摘Periodontitis can cause irreversible defects in the periodontal ligament(PDL),the regeneration of which is the major obstacle to the clinical treatment of periodontitis.Implanting hydrogel for releasing anti-inflammatory drugs is a promising treatment to promote PDL regeneration.However,existing hydrogel systems fail to mimic the typical viscoelastic feature of native periodontium,which may have been shown as an important role in tissue regeneration.Meanwhile,the synergistic benefits of mechanical cues and biochemical agents for PDL regeneration remain elusive.In this study,we developed a bi-crosslinking viscoelastic hydrogel(Alg-PBA/Spd)by integrating phenylboronic acid-modified alginate with anti-inflammatory agent(spermidine)through borate ester and B-N coordination bonds,where spermidine will be released with the degradation of the hydrogel.Alg-PBA/Spd hydrogel is biocompatible,injectable and can quickly adapt to complex periodontal structures due to the dynamic crosslinking.We demonstrated in rat models that the viscoelastic Alg-PBA/Spd hydrogel significantly promotes the deposition of periodontal collagen and accelerates the repair of periodontal damage.Our results suggest that the viscoelastic Alg-PBA/Spd hydrogel would be a promising mechano-biochemically synergistic treatment for periodontal regeneration.
