As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands...As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ regeneration.Curated by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable organs.We further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control measures.Finally,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.展开更多
Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,lim...Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.展开更多
Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathologi...Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.展开更多
Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone...Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.展开更多
An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex ...An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.展开更多
Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex b...Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex bone defects.However,final bone repair outcomes may be adversely affected by poor osteogenic capacity and risk of infection.Consequently,therapeutic methods are required that reduce bacterial contamination and increase the use of osteogenic biomaterials.Herein,we report the preparation of poly(lactic acid-coglycolic acid)(PLGA)microspheres coloaded with magnesium(Mg^(2+))and gallium(Ga^(3+))ions(Mg-Ga@PLGA),which can fill irregular bone defects and show good biosafety.During in vitro testing,Mg-Ga@PLGA not only showed a synergistic effect on promoting osteogenic differentiation but also inhibited osteoclastic differentiation.Moreover,we found that Mg-Ga@PLGA demonstrated an antibacterial effect.During in vivo testing,Mg Ga@PLGA exhibited strong in situ osteogenic ability.In conclusion,Mg-Ga@PLGA has good potential for treating bone defects at risk of infection.展开更多
Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
Wireless millirobots engineered to infiltrate intricate vascular networks within living organisms,particularly within constricted and confined spaces,hold immense promise for the future of medical treatments.However,w...Wireless millirobots engineered to infiltrate intricate vascular networks within living organisms,particularly within constricted and confined spaces,hold immense promise for the future of medical treatments.However,with their multifaceted and intricate designs,some robots often grapple with motion and functionality issues when confronted with tight spaces characterized by small cross-sectional dimensions.In this study,drawing inspiration from the high aspect ratio and undulating swimming patterns of snakes,a millimeter-scale,snake-like robot was designed and fabricated via a combination of extrusion-based four-dimensional(4D)printing and magnetic-responsive intelligent functional inks.A sophisticated motion control strategy was also developed,which enables the robots to perform various dynamic movements,such as undulating swimming,precise turns,graceful circular motions,and coordinated cluster movements,under diverse magnetic field variations.As a potential application,the snake robot can navigate and release drugs in a model coronary intervention vessel with tortuous channels and fluid filling.The novel design and promising applications of this snake robot are invaluable tools in future medical surgeries and interventions.展开更多
The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving...The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.展开更多
Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation...Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.展开更多
We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)with...We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.展开更多
As a follow-up to the successful International Conference on Biomaterials,Bio-Design and Manufacturing(BDMC)held at the National University of Singapore in 2023[1]and at the University of Tokyo in 2024[2],BDMC2025 too...As a follow-up to the successful International Conference on Biomaterials,Bio-Design and Manufacturing(BDMC)held at the National University of Singapore in 2023[1]and at the University of Tokyo in 2024[2],BDMC2025 took place at the University of Oxford in the UK from August 8th to August 10th this year.After the meeting,a participant from the University of Cambridge described his experience of attending BDMC2025 on the social media platform LinkedIn in the following terms:“Many thanks to the organizers for a fantastic event bringing together nearly everyone at the interface of Biofabrication,Materials Science,and Biomedical Engineering”[3].The conference was held on the campus of the University of Oxford and 190 researchers from 55 academic institutions across 10 countries and regions attended(Fig.1).展开更多
Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limite...Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.展开更多
This study introduces a novel concept,biological in vivo three-dimensional(3D)dose distribution verification,aimed at investigating how respiratory motion affects the efficacy of lung cancer radiotherapy,representing ...This study introduces a novel concept,biological in vivo three-dimensional(3D)dose distribution verification,aimed at investigating how respiratory motion affects the efficacy of lung cancer radiotherapy,representing an evolution from the current standard of rigid-body dose distribution verification.A 3D ex vivo biological lung motion simulation device(3D-BioLungEx)was designed to replicate human respiration.A radiotherapy plan of the patient was copied to the porcine lung,which was driven by 3D-BioLungEx to simulate various respiratory patterns that occur during treatment.To ensure anatomical consistency with the patient’s lung structure,during transmission,skin,skeleton,and organs were adjusted according to CT images of the porcine lung.The patient’s radiotherapy plan was then adapted to the porcine lung using the Monaco treatment planning system(TPS).Next,an iterative optimization and scatter inversion-based dose distribution retro-analysis algorithm(IOSI-BLDose)was developed to calculate the dose distribution during treatment.Gamma passing rates were used to quantify discrepancies between this dose distribution and that of the radiotherapy plan.When respiratory conditions were replicated,the passing rate reached up to 93.61%,while irregular breathing dropped it to 70%-90%,primarily due to amplitude changes.However,cycle variations had minimal impact.Compared to conventional rigid-body dose distribution verification,our method provides real-time biological feedback and more effectively captures motion-induced deviations.Accordingly,our biological in vivo 3D dose distribution verification has potential for improving treatment precision and enabling adaptive radiotherapy in clinical practice.展开更多
Periodontitis is an inflammatory disease caused by oxidative stress and initiated by bacterial infection.The endogenous enzyme system is dysfunctional in the periodontitis microenvironment.Currently,traditional clinic...Periodontitis is an inflammatory disease caused by oxidative stress and initiated by bacterial infection.The endogenous enzyme system is dysfunctional in the periodontitis microenvironment.Currently,traditional clinical treatment cannot efficiently eliminate bacteria or relieve inflammation.To address this issue,we developed ultrasmall ruthenium nanoparticles(US-RuNPs)with multienzyme-like activity.Our results indicated that US-RuNPs with an amplified electric field had a superior photothermal effect to large-sized RuNPs.Thus,US-RuNPs,through photothermal therapy(PTT),acted as“bacterial lysozyme”to eliminate planktonic pathogens and biofilms.In addition,the antioxidant enzyme-like activity of US-RuNPs was greater than that of large-sized RuNPs,and US-RuNPs could scavenge intracellular reactive oxygen species(ROS)and inhibit inflammation-related responses.More importantly,US-RuNPs demonstrated a satisfactory effect against periodontitis in vivo due to their synergistic antibacterial activity through PTT and antioxidant effects even in deep sites,decreasing the alveolar bone loss to root length ratio(ABL/RL)from 70.70%to 20.15%and increasing the collagen volume fraction from 16.88%to 57.64%.Thus,US-RuNPs with approximately 2 nm diameter,mimicking multienzyme activity,have great potential for the treatment of periodontitis.展开更多
The SafeAmpCase is an innovative 3D-printed solution developed to address critical challenges in transporting and storing fragile glass drug ampoules during emergencies.This study employs a multidisciplinary approach...The SafeAmpCase is an innovative 3D-printed solution developed to address critical challenges in transporting and storing fragile glass drug ampoules during emergencies.This study employs a multidisciplinary approach—integrating biomedical engineering,advanced materials science,and emergency medicine expertise—to develop a compact,durable,and user-friendly ampoule case.A key innovation lies in the strategic selection of thermoplastic polyurethane(TPU)as the material,leveraging its superior impact resistance,flexibility,and noise-damping characteristics to ensure reliability under performance in demanding real-world conditions.To optimize the 3D printing process,key parameters,including printing temperature(220-250℃),volumetric flow rate(3-20 mm^(3)/s),retraction speed(30-90 mm/s),and retraction length(0.4-1.2 mm),were systematically adjusted using calibration models.The final optimized parameters(245℃,7 mm^(3)/s,90 mm/s,and 1.2 mm)reduced production time by 43%while preserving structural integrity.American Society for Testing and Materials(ASTM)international standard drop tests confirmed the case’s exceptional impact resistance,demonstrating a 90%reduction in ampoule breakage compared to polylactic acid plus.Further refinements,guided by feedback from 25 emergency professionals,resulted in medicationspecific color coding and an enhanced locking mechanism for usability in high-pressure situations.The final SafeAmpCase model withstood 18 consecutive drop trials without ampoule breakage,confirming its robustness in field conditions.This research underscores the transformative potential of additive manufacturing in developing customized,high-performance solutions for critical healthcare applications,setting a new benchmark for biomedical device design and rapid prototyping.展开更多
A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interact...A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interactions,fostering cell growth,differentiation,and organization.However,challenges persist in decellularization,necessitating a balance between preserving the ECM structural integrity and achieving effective cellular removal.An approach to enhancing decellularization involves pre-eliminating unnecessary tissues and effectively reducing final DNA levels to lower than 50 ng/mg ECM on preprocessed tissues.Although this strategic step augments decellularization efficiency,the current manual execution method depends on the operator’s skill.To address this limitation,this study proposed an automated raw tissue slicing system that does not require tissue preparation for slicing.Through carefully controlled tissue applanation pressure and oscillatory incisions with optimized parameters,the system achieved a precision within±10µm in obtaining submillimeter-scale tissue slices of the porcine cornea while avoiding significant microscopic complications in the tissue structure,as observed by tissue histology.These findings suggested the system’s capability to streamline and automate preliminary tissue slicing operations.The efficacy of this approach for decellularization was validated by processing porcine corneas using the proposed system and subsequently decellularizing the processed tissues.DNA level analysis revealed that sliced,subdivided tissues created by this system could expedite DNA reduction even at the initial steps of decellularization,enhancing the overall decellularization procedure.展开更多
The global demand for in vitro respiratory airway models has surged due to the coronavirus disease 2019(COVID-19)pandemic.Current state-of-the-art models use polymer membranes to separate epithelial cells from other c...The global demand for in vitro respiratory airway models has surged due to the coronavirus disease 2019(COVID-19)pandemic.Current state-of-the-art models use polymer membranes to separate epithelial cells from other cell types,creating a nonphysiological barrier.In this study,we applied three-dimensional(3D)printing and bioprinting to develop an in vitro model where endothelial and epithelial cells were in direct contact,mimicking their natural arrangement.This proof-ofconcept model includes a culture chamber,with an endothelial bioink printed and perfused through an epithelial channel.In silico simulations of the air velocity within the channel revealed shear stress values ranging from 0.13 to 0.39 Pa,aligning with the desired in vivo shear stress observed in the bronchi regions(0.1–0.4 Pa).Biomechanical movements during resting breathing were mimicked by incorporating a textile mesh positioned away from the cell–cell interface.The epithelial channel demonstrated a capacity for compression and expansion of up to−14.7%and+6.4%,respectively.Microscopic images showed that the epithelial cells formed a uniform monolayer within the lumen of the channel close to the bioprinted endothelial cells.Our novel model offers a valuable tool for future research into respiratory diseases and potential treatments under conditions closely mimicking those in the lung.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52325504,52235007,and T2121004).
文摘As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ regeneration.Curated by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable organs.We further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control measures.Finally,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.
基金supported by the National Natural Science Foundation of China(No.52105072)Zhejiang Provincial Natural Science Foundation of China(No.LZ24E050004)+2 种基金Jiangsu Provincial Outstanding Youth Program(No.BK20230072)a grant from Suzhou Industrial Foresight and Key Core Technology Project(No.SYC2022044)grants from Jiangsu Qinglan Project and Jiangsu 333 High-level Talents.
文摘Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.
基金supported by the National Natural Science Foundation of China(Nos.82370322 to CC,82200352 to FZ,82300352 to YZ,22275034 to HX,and 82070343 to MLC)the Natural Science Foundation of Jiangsu Province of China(Nos.BK20220710 to FZ and BK20230733 to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.JX13414086 to HYC).
文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.
基金supported by the Science and Technology Development Fund of the Fourth Military Medical University(No.2016XB051)the Military Medical Promotion Plan of the Fourth Military Medical University(No.2016TSA-005)+2 种基金the Science and Technology Program of Guangzhou(No.201604040002)the Youth Development Project of Air Force Medical University(No.21QNPY072)the Xijing Hospital Booster Program(No.XJZT24CZ10).
文摘Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.
基金supported by the National Key Research and Development Program of China(No.2024YFA1300128)the National Natural Science Foundation of China(No.82372663)+2 种基金the Key Research and Development Program of Yunnan Province(No.202302AA310024)the Key Research and Development Program of Jiangxi Province(No.20232BBG70024)the Natural Science Foundation of Shandong Province(No.ZR2023LSW008).
文摘An organoid is a three-dimensional(3D)cell culture model that can reproduce the distinct structure and inherent functionality of certain organs.Nevertheless,a major limitation of organoids is the absence of a complex vascular network,thus restricting the supply of oxygen and essential nutrients.Coupled with their inherent size constraints and metabolite accumulation,it is challenging for organoids to replicate the natural intricacies of organs,thereby limiting their applicability.To overcome the challenges associated with this technology,we developed a culture platform to cultivate tumors or organ-derived organoids up to the centimeter scale.Initially,a customized organoid-on-a-chip including a microvascular network at the micron scale was designed using 3D printing.Further,by integrating an infusion device,the chip ensures an adequate supply of nutrients and fluid immersion while mimicking blood flow dynamics.Our method overcomes the issue of the limited size of organoids due to insufficient nutrient access,making it possible to produce large-scale tumor and normal tissue models in vitro,while providing insights into drug efficacy and toxicology evaluation as well as standardized organoid production.
基金supported by grants from the National Natural Science Foundation of China(Nos.31971106,BWS21L013,and 21WS09002).
文摘Bone defects have serious economic and clinical impacts;however,despite improvements in bone defect management,the range of clinical outcomes remains limited.A variety of biomaterials have been used to treat complex bone defects.However,final bone repair outcomes may be adversely affected by poor osteogenic capacity and risk of infection.Consequently,therapeutic methods are required that reduce bacterial contamination and increase the use of osteogenic biomaterials.Herein,we report the preparation of poly(lactic acid-coglycolic acid)(PLGA)microspheres coloaded with magnesium(Mg^(2+))and gallium(Ga^(3+))ions(Mg-Ga@PLGA),which can fill irregular bone defects and show good biosafety.During in vitro testing,Mg-Ga@PLGA not only showed a synergistic effect on promoting osteogenic differentiation but also inhibited osteoclastic differentiation.Moreover,we found that Mg-Ga@PLGA demonstrated an antibacterial effect.During in vivo testing,Mg Ga@PLGA exhibited strong in situ osteogenic ability.In conclusion,Mg-Ga@PLGA has good potential for treating bone defects at risk of infection.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
基金the National Natural Science Foundation of China(Nos.52105421 and 52373050)the Guangdong Provincial Natural Science Foundation,China(No.2022A1515011621)+1 种基金the Science and Technology Projects in Guangzhou,China(Nos.202102080330 and 2024A04J6446)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.22qntd0101).
文摘Wireless millirobots engineered to infiltrate intricate vascular networks within living organisms,particularly within constricted and confined spaces,hold immense promise for the future of medical treatments.However,with their multifaceted and intricate designs,some robots often grapple with motion and functionality issues when confronted with tight spaces characterized by small cross-sectional dimensions.In this study,drawing inspiration from the high aspect ratio and undulating swimming patterns of snakes,a millimeter-scale,snake-like robot was designed and fabricated via a combination of extrusion-based four-dimensional(4D)printing and magnetic-responsive intelligent functional inks.A sophisticated motion control strategy was also developed,which enables the robots to perform various dynamic movements,such as undulating swimming,precise turns,graceful circular motions,and coordinated cluster movements,under diverse magnetic field variations.As a potential application,the snake robot can navigate and release drugs in a model coronary intervention vessel with tortuous channels and fluid filling.The novel design and promising applications of this snake robot are invaluable tools in future medical surgeries and interventions.
基金supported in part by the National Natural Science Foundation of China(Nos.52205532 and 624B2077)the National Key Research and Development Program of China(No.2023YFB4302003).
文摘The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)the Shanxi Provincial Key Medical Scientific Research Project(No.2020XM06)+2 种基金the Shanxi Provincial Basic Research Project(Nos.202103021221006,20210302123040,and 202103021223069)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.
基金supported by the National Natural Science Foundation of China(Nos.32371470 and 82341019)the Department of Science and Technology of Guangdong Province(No.2023B0909020003).
文摘We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.
文摘As a follow-up to the successful International Conference on Biomaterials,Bio-Design and Manufacturing(BDMC)held at the National University of Singapore in 2023[1]and at the University of Tokyo in 2024[2],BDMC2025 took place at the University of Oxford in the UK from August 8th to August 10th this year.After the meeting,a participant from the University of Cambridge described his experience of attending BDMC2025 on the social media platform LinkedIn in the following terms:“Many thanks to the organizers for a fantastic event bringing together nearly everyone at the interface of Biofabrication,Materials Science,and Biomedical Engineering”[3].The conference was held on the campus of the University of Oxford and 190 researchers from 55 academic institutions across 10 countries and regions attended(Fig.1).
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
文摘Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
基金funded by the National Natural Science Foundation of China (No. 81960334)the Guiding Plan of Xinjiang Production Construction Corps (No. 2022ZD007)+4 种基金the Science and Technology Innovation Leading Talents Program of Guangdong Province (No. 2019TX05C343)the Basic and Applied Basic Research Foundation of Guangdong Province-Regional Joint Fund-Key Projects (No. 2019B1515120043)the Project supported by the State Key Laboratory of Luminescence and Applications (No. SKLA-2020-03)the support from Instrumental Analysis Center of Shenzhen University (Xili Campus)Instrumental Analysis Center of Shihezi University.
文摘Ischemic stroke is the leading cause of death in China,accounting for approximately one-third of all stroke-associated deaths worldwide.Currently,thrombolysis is employed for ischemic strokes.However,due to the limited therapeutic window of thrombolytic agents,most patients do not receive the drug at the right time.Moreover,these agents are associated with risks of hemorrhage and reperfusion damage.Herein,Angiopep-2(ANG)-black phosphorus(BP)-resveratrol(RES),a drug-loaded system,was used to deliver drugs across the blood–brain barrier(BBB).ANG-BP-RES has a uniform size,stable structure,good photothermal effect,and strong drug release ability under near-infrared(NIR)irradiation and acidic conditions.Furthermore,ANG-BP-RES can efficiently target the brain and improve BBB permeability,exerting a significant therapeutic effect against ischemic brain injury,especially after NIR irradiation.ANG-BP-RES is also biocompatible and shows minimal toxicity toward cells and tissues.This study offers novel insights into the therapeutic management of ischemic brain injury.
基金supported by the National Natural Science Foundation of China(No.62371243)National Key Research and Development Program of China(No.2025YFC2427600)+4 种基金the Jiangsu Provincial Key Research and Development Program Social Development Project(No.BE2022720)the Natural Science Foundation of Jiangsu Province(No.BK20231190)Jiangsu Provincial Medical Key Discipline Cultivation Unit of Oncology Therapeutics(Radiotherapy)(No.JSDW202237)Changzhou Social Development Program(Nos.CE20235063 and CJ20244020)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.JX13614239).
文摘This study introduces a novel concept,biological in vivo three-dimensional(3D)dose distribution verification,aimed at investigating how respiratory motion affects the efficacy of lung cancer radiotherapy,representing an evolution from the current standard of rigid-body dose distribution verification.A 3D ex vivo biological lung motion simulation device(3D-BioLungEx)was designed to replicate human respiration.A radiotherapy plan of the patient was copied to the porcine lung,which was driven by 3D-BioLungEx to simulate various respiratory patterns that occur during treatment.To ensure anatomical consistency with the patient’s lung structure,during transmission,skin,skeleton,and organs were adjusted according to CT images of the porcine lung.The patient’s radiotherapy plan was then adapted to the porcine lung using the Monaco treatment planning system(TPS).Next,an iterative optimization and scatter inversion-based dose distribution retro-analysis algorithm(IOSI-BLDose)was developed to calculate the dose distribution during treatment.Gamma passing rates were used to quantify discrepancies between this dose distribution and that of the radiotherapy plan.When respiratory conditions were replicated,the passing rate reached up to 93.61%,while irregular breathing dropped it to 70%-90%,primarily due to amplitude changes.However,cycle variations had minimal impact.Compared to conventional rigid-body dose distribution verification,our method provides real-time biological feedback and more effectively captures motion-induced deviations.Accordingly,our biological in vivo 3D dose distribution verification has potential for improving treatment precision and enabling adaptive radiotherapy in clinical practice.
基金supported by the National Key Research and Development Program of China(No.2023YFB3813000)the National Natural Science Foundation of China(Nos.82071085,82020108011,and 82122014)the Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001).
文摘Periodontitis is an inflammatory disease caused by oxidative stress and initiated by bacterial infection.The endogenous enzyme system is dysfunctional in the periodontitis microenvironment.Currently,traditional clinical treatment cannot efficiently eliminate bacteria or relieve inflammation.To address this issue,we developed ultrasmall ruthenium nanoparticles(US-RuNPs)with multienzyme-like activity.Our results indicated that US-RuNPs with an amplified electric field had a superior photothermal effect to large-sized RuNPs.Thus,US-RuNPs,through photothermal therapy(PTT),acted as“bacterial lysozyme”to eliminate planktonic pathogens and biofilms.In addition,the antioxidant enzyme-like activity of US-RuNPs was greater than that of large-sized RuNPs,and US-RuNPs could scavenge intracellular reactive oxygen species(ROS)and inhibit inflammation-related responses.More importantly,US-RuNPs demonstrated a satisfactory effect against periodontitis in vivo due to their synergistic antibacterial activity through PTT and antioxidant effects even in deep sites,decreasing the alveolar bone loss to root length ratio(ABL/RL)from 70.70%to 20.15%and increasing the collagen volume fraction from 16.88%to 57.64%.Thus,US-RuNPs with approximately 2 nm diameter,mimicking multienzyme activity,have great potential for the treatment of periodontitis.
基金Open access funding provided by Ben-Gurion University.
文摘The SafeAmpCase is an innovative 3D-printed solution developed to address critical challenges in transporting and storing fragile glass drug ampoules during emergencies.This study employs a multidisciplinary approach—integrating biomedical engineering,advanced materials science,and emergency medicine expertise—to develop a compact,durable,and user-friendly ampoule case.A key innovation lies in the strategic selection of thermoplastic polyurethane(TPU)as the material,leveraging its superior impact resistance,flexibility,and noise-damping characteristics to ensure reliability under performance in demanding real-world conditions.To optimize the 3D printing process,key parameters,including printing temperature(220-250℃),volumetric flow rate(3-20 mm^(3)/s),retraction speed(30-90 mm/s),and retraction length(0.4-1.2 mm),were systematically adjusted using calibration models.The final optimized parameters(245℃,7 mm^(3)/s,90 mm/s,and 1.2 mm)reduced production time by 43%while preserving structural integrity.American Society for Testing and Materials(ASTM)international standard drop tests confirmed the case’s exceptional impact resistance,demonstrating a 90%reduction in ampoule breakage compared to polylactic acid plus.Further refinements,guided by feedback from 25 emergency professionals,resulted in medicationspecific color coding and an enhanced locking mechanism for usability in high-pressure situations.The final SafeAmpCase model withstood 18 consecutive drop trials without ampoule breakage,confirming its robustness in field conditions.This research underscores the transformative potential of additive manufacturing in developing customized,high-performance solutions for critical healthcare applications,setting a new benchmark for biomedical device design and rapid prototyping.
基金supported by the Alchemist Project 1415180884(No.20012378,Development of Meta Soft Organ Module Manufacturing Technology without Immunity Rejection and Module Assembly Robot System)funded by the Ministry of Trade,Industry&Energy(MOTIE,Republic of Korea)the Technology Development Program(No.S3318933)funded by the Ministry of SMEs and Startups(MSS,Republic of Korea).
文摘A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interactions,fostering cell growth,differentiation,and organization.However,challenges persist in decellularization,necessitating a balance between preserving the ECM structural integrity and achieving effective cellular removal.An approach to enhancing decellularization involves pre-eliminating unnecessary tissues and effectively reducing final DNA levels to lower than 50 ng/mg ECM on preprocessed tissues.Although this strategic step augments decellularization efficiency,the current manual execution method depends on the operator’s skill.To address this limitation,this study proposed an automated raw tissue slicing system that does not require tissue preparation for slicing.Through carefully controlled tissue applanation pressure and oscillatory incisions with optimized parameters,the system achieved a precision within±10µm in obtaining submillimeter-scale tissue slices of the porcine cornea while avoiding significant microscopic complications in the tissue structure,as observed by tissue histology.These findings suggested the system’s capability to streamline and automate preliminary tissue slicing operations.The efficacy of this approach for decellularization was validated by processing porcine corneas using the proposed system and subsequently decellularizing the processed tissues.DNA level analysis revealed that sliced,subdivided tissues created by this system could expedite DNA reduction even at the initial steps of decellularization,enhancing the overall decellularization procedure.
基金supported by the Volkswagen Foundation(Grant No.Az 99078 to DDC,ALT,and MT)funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany’s Excellence Strategy–2082/1–390761711(to DDC)part of the research training group GRK 2415–Mechanobiology in Epithelial 3D Tissue Constructs(project number 363055819,to ALT and SJ).
文摘The global demand for in vitro respiratory airway models has surged due to the coronavirus disease 2019(COVID-19)pandemic.Current state-of-the-art models use polymer membranes to separate epithelial cells from other cell types,creating a nonphysiological barrier.In this study,we applied three-dimensional(3D)printing and bioprinting to develop an in vitro model where endothelial and epithelial cells were in direct contact,mimicking their natural arrangement.This proof-ofconcept model includes a culture chamber,with an endothelial bioink printed and perfused through an epithelial channel.In silico simulations of the air velocity within the channel revealed shear stress values ranging from 0.13 to 0.39 Pa,aligning with the desired in vivo shear stress observed in the bronchi regions(0.1–0.4 Pa).Biomechanical movements during resting breathing were mimicked by incorporating a textile mesh positioned away from the cell–cell interface.The epithelial channel demonstrated a capacity for compression and expansion of up to−14.7%and+6.4%,respectively.Microscopic images showed that the epithelial cells formed a uniform monolayer within the lumen of the channel close to the bioprinted endothelial cells.Our novel model offers a valuable tool for future research into respiratory diseases and potential treatments under conditions closely mimicking those in the lung.
