Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the an...Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.展开更多
Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the re...Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the requirements of common applications,e.g.,the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests.Here,we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics.Double-layer 3D microfluidic structures can be produced by replicating the assembled molds.A library of modularized molds is presented for flow control,droplet generation and manipulation and cell trapping and coculture.In addition,a variety of modularized attachments,including valves,light sources and microscopic cameras,have been developed with the capability to be mounted onto chips on demand.Microfluidic systems,including those for concentration gradient generation,droplet-based microfluidics,cell trapping and drug screening,are demonstrated.This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms,with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.展开更多
基金supported by research grants from the National Natural Science Foundation of China(82122017,82271069 and 81900839)Shanghai Science and Technology Commission(22xtcx00103)Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(SHDC12019X08,SHDC12020111 and SHDC2020CR4078).
文摘Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.
基金supported by grants from the National Special Fund for the Development of Major Research Equipment and Instrument(Grant No.2020YFF01014503)National Natural Science Foundation of China(Grant No.61775140)+1 种基金Shanghai Industrial Collaborative Innovation Project(Grant No.2021-cyxt1-kj06)Shanghai Rising-Star Program(Grant No.20QA1407000).
文摘Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems.Nevertheless,the strategy of directly integrating modules cannot easily fulfill the requirements of common applications,e.g.,the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests.Here,we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics.Double-layer 3D microfluidic structures can be produced by replicating the assembled molds.A library of modularized molds is presented for flow control,droplet generation and manipulation and cell trapping and coculture.In addition,a variety of modularized attachments,including valves,light sources and microscopic cameras,have been developed with the capability to be mounted onto chips on demand.Microfluidic systems,including those for concentration gradient generation,droplet-based microfluidics,cell trapping and drug screening,are demonstrated.This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms,with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.