Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis,angiosteosis,and vascular aging.Increased stiffness of the vascular ex...Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis,angiosteosis,and vascular aging.Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell.Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering,regenerative medicine,and medical devices.Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells(VECs)and smooth muscle cells(VSMCs).Interestingly,our findings demonstrate that,with the increase of substrate stiffness,the autophagy level of VECs and VSMCs showed differential changes:endothelial autophagy levels reduced,leading to the reductions in a range of gene expression associated with endothelial function;while,autophagy levels of VSMCs increased,showing a transition from contractile to the synthetic phenotype.We further demonstrate that,by inhibiting cell autophagy,the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased,suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing.Although the underlying mechanism requires further study,this work highlights the relationship of substrate stiffness,autophagy,and vascular cell behaviors,and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications.展开更多
Porous coatings with the features of muti-interfaces and high specific surface area have emerged as an excellent material platform for the manipulation of porous structures.Layer-by-layer(Lb L)assembly technique has b...Porous coatings with the features of muti-interfaces and high specific surface area have emerged as an excellent material platform for the manipulation of porous structures.Layer-by-layer(Lb L)assembly technique has been widely used in preparing porous polyelectrolyte coatings.However,the efficient construction of stable film from the Lb L technique is still a question.Herein,we reported a new solution to construct a stabilized polyelectrolyte coating with porous structures.Inspired by the mechanical reinforcement of double-network hydrogel,we constructed the poly(ethylenimine)(PEI)/poly(acrylic acid)(PAA)coating by in situ photopolymerization of acrylic acid in the PEI network instead of assembling PEI and PAA.Compared with the Lb L films,the in situ polymerized coating kept higher stability after 30 iterations of friction.Porous structures could also be constructed after acid treatment,which was utilized to load lubricant to enhance the lubricating property of the coating.This work provides a new method for the construction of dynamic and stable polyelectrolyte coatings,expediting more development of practical applications.展开更多
The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial ...The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells(EC)and smooth muscle cells(SMC)in response to vascular injury,providing a promising therapeutic candidate to inhibit IRS.However,the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings.Here,we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)(PCL-PEG-PCL,PCEC)triblock copolymer spongy network.The miR-22 was used as a model microRNA to regulate SMC.The dynamic porous coating realized the uniform and controllable loading of miR-22,reaching the highest dosage of 133 pmol cm^(-2).We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC,thus leading to the EC dominating growth at an EC/SMC ratio of 5.4.More importantly,the PCEC@miR-22 coated stents showed reduced inflammation,low switching of SMC phenotype,and low secretion of extracellular matrix,which significantly inhibited IRS.This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent,which may extend to other combination medical devices,and facilitate practical application of bioactive agents in clinics.展开更多
The developments of tough hydrogels in recent years have greatly expanded the applications of hydrogels as structural materials. However, most of the tough hydrogels are made of synthetic polymers. To develop biopolym...The developments of tough hydrogels in recent years have greatly expanded the applications of hydrogels as structural materials. However, most of the tough hydrogels are made of synthetic polymers. To develop biopolymer-based tough hydrogels has both fundamental and practical significances. Here we report a series of polysaccharides-based tough hydrogel films prepared by polyion complexation and solvent evaporation of chondroitin sulfate(CS) and protonated chitosan(CHT) solutions with different weight ratios. The obtained CS/CHT gel films with thickness of 40-80 μm and water content of 66 wt%-81 wt% possess excellent mechanical properties, with tensile breaking stress and breaking strain being 0.4-3 MPa and 160%-320%, respectively. We found that in the mixture solutions there are large amounts of excess CHT in terms of charges; after swelling the films in water, the acetic acid, which is used to protonate the amino groups of CHT, diffuses out of the gel matrix, enhancing the intermolecular interactions between CHT molecules and thus improving the mechanical properties of gel films, besides the ionic bonds between CS and CHT. Antimicrobial tests also showed that the gel films with low weight ratio of CS to CHT, corresponding to the case with excess CHT, have evident antimicrobial effect. These CS/CHT gel films with good mechanical properties and antimicrobial effect should extend the applications of hydrogels in biomedical fields.展开更多
基金supported by Zhejiang Provincial Natural Science Foundation of China (LD22E030008)National Natural Science Foundation of China (U20A20262)+2 种基金the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2022483477)the Fundamental Research Funds for the Central Universities (226-2023-00074)supported by Zhejiang University K. P. Chao’s High Technology Development Foundation
基金supported by the National Natural Science Foundation of China(21875210)the National Key Research and Development Program of China(2016YFC1102203)+3 种基金the Natural Key Research and Development Project of Zhejiang Province(2018C03015)Zhejiang Provincial Ten Thousand Talents Program(2018R52001)the Fundamental Research Funds for the Central Universities(2020FZZX003-01-03)the Higher Education Discipline Innovation Project(111 Project)under Grant No.B16042.
文摘Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis,angiosteosis,and vascular aging.Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell.Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering,regenerative medicine,and medical devices.Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells(VECs)and smooth muscle cells(VSMCs).Interestingly,our findings demonstrate that,with the increase of substrate stiffness,the autophagy level of VECs and VSMCs showed differential changes:endothelial autophagy levels reduced,leading to the reductions in a range of gene expression associated with endothelial function;while,autophagy levels of VSMCs increased,showing a transition from contractile to the synthetic phenotype.We further demonstrate that,by inhibiting cell autophagy,the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased,suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing.Although the underlying mechanism requires further study,this work highlights the relationship of substrate stiffness,autophagy,and vascular cell behaviors,and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications.
基金financially supported by the National Natural Science Foundation of China(No.U20A20262)Zhejiang Provincial Natural Science Foundation of China(No.LD22E030008)+1 种基金the Zhejiang Provincial Ten Thousand Talents Program(No.2018R52001)Fundamental Research Funds for the Central Universities(No.2021FZZX003-01-03)。
文摘Porous coatings with the features of muti-interfaces and high specific surface area have emerged as an excellent material platform for the manipulation of porous structures.Layer-by-layer(Lb L)assembly technique has been widely used in preparing porous polyelectrolyte coatings.However,the efficient construction of stable film from the Lb L technique is still a question.Herein,we reported a new solution to construct a stabilized polyelectrolyte coating with porous structures.Inspired by the mechanical reinforcement of double-network hydrogel,we constructed the poly(ethylenimine)(PEI)/poly(acrylic acid)(PAA)coating by in situ photopolymerization of acrylic acid in the PEI network instead of assembling PEI and PAA.Compared with the Lb L films,the in situ polymerized coating kept higher stability after 30 iterations of friction.Porous structures could also be constructed after acid treatment,which was utilized to load lubricant to enhance the lubricating property of the coating.This work provides a new method for the construction of dynamic and stable polyelectrolyte coatings,expediting more development of practical applications.
基金This research was supported by the National Key Research and Development Program of China(2016YFC1102203)the National Natural Science Foundation of China(51933009,21875210)+3 种基金the Natural Key Research and Development Project of Zhejiang Province(2018C03015)Zhejiang Provincial Ten Thousand Talents Program(2018R52001)the Fundamental Research Funds for the Central Universities(2020FZZX003-01-03)the Higher Education Discipline Innovation Project(111 Project)under Grant No.B16042.
文摘The in-stent restenosis(IRS)after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation.MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells(EC)and smooth muscle cells(SMC)in response to vascular injury,providing a promising therapeutic candidate to inhibit IRS.However,the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings.Here,we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)(PCL-PEG-PCL,PCEC)triblock copolymer spongy network.The miR-22 was used as a model microRNA to regulate SMC.The dynamic porous coating realized the uniform and controllable loading of miR-22,reaching the highest dosage of 133 pmol cm^(-2).We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC,thus leading to the EC dominating growth at an EC/SMC ratio of 5.4.More importantly,the PCEC@miR-22 coated stents showed reduced inflammation,low switching of SMC phenotype,and low secretion of extracellular matrix,which significantly inhibited IRS.This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent,which may extend to other combination medical devices,and facilitate practical application of bioactive agents in clinics.
基金financially supported by the National Natural Science Foundation of China(No.51403184)Scientific Research Foundation for the Returned Overseas Chinese Scholars(No.J20141135)Fundamental Research Funds for the Central Universities of China
文摘The developments of tough hydrogels in recent years have greatly expanded the applications of hydrogels as structural materials. However, most of the tough hydrogels are made of synthetic polymers. To develop biopolymer-based tough hydrogels has both fundamental and practical significances. Here we report a series of polysaccharides-based tough hydrogel films prepared by polyion complexation and solvent evaporation of chondroitin sulfate(CS) and protonated chitosan(CHT) solutions with different weight ratios. The obtained CS/CHT gel films with thickness of 40-80 μm and water content of 66 wt%-81 wt% possess excellent mechanical properties, with tensile breaking stress and breaking strain being 0.4-3 MPa and 160%-320%, respectively. We found that in the mixture solutions there are large amounts of excess CHT in terms of charges; after swelling the films in water, the acetic acid, which is used to protonate the amino groups of CHT, diffuses out of the gel matrix, enhancing the intermolecular interactions between CHT molecules and thus improving the mechanical properties of gel films, besides the ionic bonds between CS and CHT. Antimicrobial tests also showed that the gel films with low weight ratio of CS to CHT, corresponding to the case with excess CHT, have evident antimicrobial effect. These CS/CHT gel films with good mechanical properties and antimicrobial effect should extend the applications of hydrogels in biomedical fields.
基金supported by the National Natural Science Foundation of China(21875210)the National Key Research and Development Program of China(2016YFC1102203)+3 种基金the Natural Key Research and Development Project of Zhejiang Province(2018C03015)Zhejiang Provincial Ten Thousand Talents Program(2018R52001)the Fundamental Research Funds for the Central Universities(2020FZZX003-01-03)the Higher Education Discipline Innovation Project(111 Project)(B16042)。