Three-dimensional(3D)bioprinting has revolutionized tissue engineering by enabling precise fabrication with bioinks.Among these techniques,digital light processing(DLP)stands out due to its exceptional resolution,spee...Three-dimensional(3D)bioprinting has revolutionized tissue engineering by enabling precise fabrication with bioinks.Among these techniques,digital light processing(DLP)stands out due to its exceptional resolution,speed,and biocompatibility.However,the progress of DLP is hindered by the limited availability of suitable bioinks.Currently,some studies involve simple mixing of different materials,resulting in bioinks that lack uniformity and photopolymerization characteristics.To address this challenge,we present an innovative one-pot synthesis method for bioinks based on methacrylated gelatin/alginate with hydroxyapatite(HAP).This approach offers significant advantages in terms of efficiency and uniformity.The synthesized bioinks demonstrate excellent printability,stability,and notably enhanced mechanical properties,facilitating optimal in vitro compatibility.Additionally,the HAP-hybrid bioinks printed scaffolds demonstrated impressive bone repair capabilities in vivo compared with pure organic bioinks.In conclusion,the Gel/Alg/HAP bioinks presented herein offer an innovative solution for DLP bioprinting within the field of bone tissue engineering.Their multifaceted advantages help overcome the limitations of restricted bioink choices,pushing forward the boundaries of bioprinting technology and contributing to the progress of regenerative medicine and tissue engineering.展开更多
Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications.However,it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resol...Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications.However,it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resolution of conventional bioprinting techniques such as extrusion-and inkjet-based printing.Recently,an electrohydrodynamic(EHD)bioprinting strategy was reported for the precise deposition of well-organized cell-laden constructs with microscale filament size,whereas few studies have been devoted to developing bioinks that can be applied for EHD bioprinting and simultaneously support cell spreading.This study describes functionalized alginate-based bioinks for microscale EHD bioprinting using peptide grafting and fibrin incorporation,which leads to high cell viability(>90%)and cell spreading.The printed filaments can be further refined to as small as 30μm by incorporating polyoxyethylene and remained stable over one week when exposed to an aqueous environment.By utilizing the presented alginate-based bioinks,layer-specific cell alignment along the printing struts could be observed inside the EHD-printed microscale filaments,which allows fabricating living constructs with cell-scale filament resolution for guided cellular orientation.展开更多
Cryobioprinting has tremendous potential to solve problems to do with lack of shelf availability in traditional bioprinting by combining extrusion bioprinting and cryopreservation.In order to ensure the viability of c...Cryobioprinting has tremendous potential to solve problems to do with lack of shelf availability in traditional bioprinting by combining extrusion bioprinting and cryopreservation.In order to ensure the viability of cells in the frozen state and avoid the possible toxicity of dimethyl sulfoxide(DMSO),DMSO-free bioink design is critical for achieving successful cryobioprinting.A nontoxic gelatin methacryloyl-based bioink used in cryobioprinting is composed of cryoprotective agents(CPAs)and a buffer solution.The selection and ratio of CPAs in the bioink directly affect the survival of cells in the frozen state.However,the development of universal and efficient cryoprotective bioinks requires extensive experimentation.We first compared two commonly used CPA formulations via experiments in this study.Results show that the effect of using ethylene glycol as the permeable CPA was 6.07%better than that of glycerol.Two datasets were obtained and four machinelearning models were established to predict experimental outcomes.The predictive powers of multiple linear regression(MLR),decision tree(DT),random forest(RF),and artificial neural network(ANN)approaches were compared,suggesting an order of ANN>RF>DT>MLR.The final selected ANN model was then applied to another dataset.Results reveal that this machine-learning method can accurately predict the effects of cryoprotective bioinks composed of different CPAs.Outcomes also suggest that the formulations presented here have universality.Our findings are likely to greatly accelerate research and development on the use of bioinks for cryobioprinting.展开更多
Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage.This study introduces a new approach that synergizes the advantages ...Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage.This study introduces a new approach that synergizes the advantages of cell compatibility of biological hydrogels and mechanical stability of elastomeric polymers for structure fidelity maintenance upon stereolithography and extrusion 3D printing.Enabling this advance is the composite bioink,formulated by integrating elastomeric microparticles from poly(octamethylene maleate(anhydride)citrate)(POMaC)into biologically derived hydrogels(fibrin,gelatin methacryloyl(GelMA),and alginate).The composite bioink enhanced the elasticity and plasticity of the 3D printed constructs,effectively mitigating tissue compaction and swelling.It exhibited a low shear modulus and a rapid crosslinking time,along with a high ultimate compressive strength and resistance to deformation from cellular forces and physical handling;this was attributed to packing and stress dissipation of elastomeric particles,which was confirmed via mathematical modelling.Enhanced functional assembly and stability of human iPSC-derived cardiac tissues and primary vasculature proved the utility of the composite bioink in tissue engineering.In vivo implantation studies revealed that constructs containing POMaC particles exhibited improved resilience against host tissue stress,enhanced angiogenesis,and infiltration of pro-reparative macrophages.展开更多
Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructi...Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructing complex biomimetic 3D architectures,which are currently restricted by the limited number of available bioinks with high printability,biomimicry,biocompatibility,and proper mechanical properties.Inspired by ubiquitous coacervation phenomena in biology,we present a unique mineral-biopolymer coacervation strategy that enables the hierarchical assembly of nanoclay and recombinant human collagen(RHC).This system was observed to undergo a coacervation transition(liquid‒liquid phase separation)spontaneously.The formed dense phase separated from its supernatant is the coacervate of clay-RHC-rich complexes,where polymer chains are sandwiched between silicate layers.Molecular dynamics simulation was first used to verify and explore the coacervation process.Then,the coacervates were demonstrated to be potential bioinks that exhibited excellent self-supporting and shear-thinning viscoelastic properties.Through extrusion-based printing,the versatility of the bioink was demonstrated by reconstructing the key features of several biological tissues,including multilayered lattice,vascular,nose,and ear-like structures,without the need for precrosslinking operations or support baths.Furthermore,the printed scaffolds were cytocompatible,elicited minimal inflammatory responses,and promoted bone regeneration in calvarial defects.展开更多
Osteosarcoma,an aggressive bone cancer found most often in children and adolescents,remains difficult to treat,and little improvement in survival rate has been observed over recent decades.The tumor microenvironment(T...Osteosarcoma,an aggressive bone cancer found most often in children and adolescents,remains difficult to treat,and little improvement in survival rate has been observed over recent decades.The tumor microenvironment(TME),especially the extracellular matrix(ECM),is a critical factor determining cancer progression and chemotherapy resistance,yet traditional 2D models generally fail to replicate its properties.Recent development of 3D-bioprinted tumor models has facilitated improved simulation of the complexity of the TME,but specific models involving bioinks tailored to osteosarcoma remain underdeveloped.Gelatin methacryloyl(GelMA)is a common bioink that can rapidly gel and contains Arg-Gly-Asp(RGD)sequences.However,it lacks collagen’s triple-helix structure that is essential for ECM-cell communication.Hyaluronic acid(HA)is a macromolecule that is aberrantly expressed in osteosarcoma by mechanisms that remain largely unexplored.In this study,we developed a composite bioink containing GelMA,collagen,and HA,and applied it to 3D bioprint an in vitro osteosarcoma model.We found that HA significantly enhanced osteosarcoma cell proliferation and chemoresistance,as well as the expression of epithelial-mesenchymal transition and cancer stem cell markers.Furthermore,we found that HA abundance was positively correlated with hypoxia and angiogenesis signaling pathways,and this occurred mainly via upregulation of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)expression,thereby contributing to increased chemoresistance.Overall,our study provides a protocol for building in vitro realistic 3D-bioprinted models for studying osteosarcoma,highlights the role of HA in osteosarcoma progression,and offers a platform for developing new chemotherapy treatments.展开更多
Bioinks are formulations of biomaterials and living cells, sometimes with growth factors or other biomolecules, while extrusion bioprinting is an emerging technique to apply or deposit these bioinks or biomaterial sol...Bioinks are formulations of biomaterials and living cells, sometimes with growth factors or other biomolecules, while extrusion bioprinting is an emerging technique to apply or deposit these bioinks or biomaterial solutions to create three-dimensional (3D) constructs with architectures and mechanical/biological properties that mimic those of native human tissue or organs. Printed constructs have found wide applications in tissue engineering for repairing or treating tissue/organ injuries, as well as in vitro tissue modelling for testing or validating newly developed therapeutics and vaccines prior to their use in humans. Successful printing of constructs and their subsequent applications rely on the properties of the formulated bioinks, including the rheological, mechanical, and biological properties, as well as the printing process. This article critically reviews the latest developments in bioinks and biomaterial solutions for extrusion bioprinting, focusing on bioink synthesis and characterization, as well as the influence of bioink properties on the printing process. Key issues and challenges are also discussed along with recommendations for future research.展开更多
The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dim...The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and protection.In this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner.After gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from GelMA.The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell viability.The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion.Furthermore,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials distribution.Overall,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.展开更多
Extrusion-based bioprinting (EBB) holds potential for regenerative medicine. However, the widely-used bioinks of EBB exhibit some limitations for skin regeneration, such as unsatisfactory bio-physical (i.e., mechanica...Extrusion-based bioprinting (EBB) holds potential for regenerative medicine. However, the widely-used bioinks of EBB exhibit some limitations for skin regeneration, such as unsatisfactory bio-physical (i.e., mechanical, structural, biodegradable) properties and compromised cellular compatibilities, and the EBB-based bioinks with therapeutic effects targeting cutaneous wounds still remain largely undiscussed. In this review, the printability considerations for skin bioprinting were discussed. Then, current strategies for improving the physical properties of bioinks and for reinforcing bioinks in EBB approaches were introduced, respectively. Notably, we highlighted the applications and effects of current EBB-based bioinks on wound healing, wound scar formation, vasculari-zation and the regeneration of skin appendages (i.e., sweat glands and hair follicles) and discussed the challenges and future perspectives. This review aims to provide an overall view of the applications, challenges and promising solutions about the EBB-based bioinks for cutaneous wound healing and skin regeneration.展开更多
In the field of regenerative medicine,the importance of 3D bioprinting is self-evident and nonnegligible.However,3D bioprinting technology also requires bioink with excellent performance as support material to fabrica...In the field of regenerative medicine,the importance of 3D bioprinting is self-evident and nonnegligible.However,3D bioprinting technology also requires bioink with excellent performance as support material to fabricate a multi-functional bioinspired scaffold.Collagen-based bioink is regarded as an ideal 3D bioprinting ink for its excellent biocompatibility,controllable printability and cell loading property.It is an important breakthrough in regenerative medicine with the progress of collagen-based bioink,which fabricates bioinspired scaffolds with different functions and is applied in different repair scenarios.This review summarizes the different applications of collagen-based bioink and classifies them as soft tissue and hard tissue according to the target region.The applications of target region in soft tissues include skin,cartilage,heart and blood vessels,while in hard tissues include femur,skull,teeth and spine.When the collagen-based bioink is applied in repairing soft tissue,the requirements of function are higher,while the mechanical properties must be further improved in repairing hard tissue.We further summarize the characteristics of collagen-based bioink and point out the most important properties that should be considered in different repair scenarios,which can provide reference for the preparation of bioinks with different functions.Finally,we point out the main challenges faced by collagen-based bioink and prospect the future research directions.展开更多
In recent years,significant progress has been made in both three-dimensional(3D)printing technologies and the exploration of silk as an ink to produce biocompatible constructs.Combined with the unlimited design potent...In recent years,significant progress has been made in both three-dimensional(3D)printing technologies and the exploration of silk as an ink to produce biocompatible constructs.Combined with the unlimited design potential of 3D printing,silk can be processed into a broad range of functional materials and devices for various biomedical applications.The ability of silk to be processed into various materials,including solutions,hydrogels,particles,microspheres,and fibers,makes it an excellent candidate for adaptation to different 3D printing techniques.This review presents a didactic overview of the 3D printing of silk-based materials,major categories of printing techniques,and their prototyping mechanisms and structural features.In addition,we provide a roadmap for researchers aiming to incorporate silk printing into their own work by summarizing promising strategies from both technical and material aspects,to relate state-of-the-art silk-based material processing with fast-developing 3D printing technologies.Thus,our focus is on elucidating the techniques and strategies that advance the development of precise assembly strategies for silk-based materials.Precise printing(including high printing resolution,complex structure realization,and printing fidelity)is a prerequisite for the digital design capability of 3D printing technology and would definitely broaden the application era of silk,such as complex biomimetic tissue structures,vasculatures,and transdermal microneedles.展开更多
Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessita...Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.展开更多
Three-dimensional(3D)bioprinting,which has been applied in tissue engineering and regenerative medicine,uses biomaterials,cells,and other essential components to manufacture organs and tissues with specific biological...Three-dimensional(3D)bioprinting,which has been applied in tissue engineering and regenerative medicine,uses biomaterials,cells,and other essential components to manufacture organs and tissues with specific biological functions and complex structures.Over the past 30 years,researchers have developed new 3D bioprinting technologies with improved manufacturing capabilities and expanded applications.Chinese research teams contributed significantly to this process.In this paper,we first reviewed the development history and major milestones in 3D bioprinting,categorizing them into two main strategies:"biomaterial-based indirect assembly"and"living cell-based direct assembly".This review further delved into the technical principles,recent advancements,advantages,disadvantages,and applications of each type of bioprinting technology.Finally,the challenges and future directions of 3D bioprinting were summarized to guide future research in China and foster advancements in this dynamic field.展开更多
Bioprinting is emerging as an advanced tool in tissue engineering.However,there is still a lack of bioinks able to form hydrogels with desirable bioactivities that support positive cell behaviors.In this study,modifie...Bioprinting is emerging as an advanced tool in tissue engineering.However,there is still a lack of bioinks able to form hydrogels with desirable bioactivities that support positive cell behaviors.In this study,modified plasma proteins capable of forming hydrogels with multiple biological functions are developed as bioinks for digital light processing(DLP)printing.The Plasma-MA(BM)was synthesized via a one-pot method through the reaction between the fresh frozen plasma and methacrylic anhydride.The methacry-lated levels were observed to influence the physical properties of BM hydrogels including mechanical properties,swelling,and degradation.The photo-crosslinked BM hydrogels can sustainedly release vascu-lar endothelial growth factor(VEGF)and exhibit positive biological effects on cell adhesion and prolifer-ation,and cell functionality such as tube formation of human umbilical vein endothelial cells(HUVECs),and neurite elongation of rat pheochromocytoma cells(PC12).Meanwhile,BM hydrogels can also induce cell infiltration,modulate immune response,and promote angiogenesis in vivo.Moreover,the plasma bioinks can be used to fabricate customized scaffolds with complex structures through a DLP printing process.These findings implicate that the modified plasma with growth factor release is a promising candidate for bioprinting in autologous and personalized tissue engineering.展开更多
Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-en...Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.展开更多
Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for effi...Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for efficacious cartilage repair,and long-term patient outcomes are not satisfying.Three-dimensional bioprinting has been used to fabricate biochemical and biophysical environments that aim to recapitulate the native microenvironment and promote tissue regeneration.However,conventional in vitro bioprinting has limitations due to the challenges associated with the fabrication and implantation of bioprinted constructs and their integration with the native cartilage tissue.In situ bioprinting is a novel strategy to directly deliver bioinks to the desired anatomical site and has the potential to overcome major shortcomings associated with conventional bioprinting.In this review,we focus on the new frontier of robotic-assisted in situ bioprinting surgical systems for cartilage regeneration.We outline existing clinical approaches and the utilization of robotic-assisted surgical systems.Handheld and robotic-assisted in situ bioprinting techniques including minimally invasive and non-invasive approaches are defined and presented.Finally,we discuss the challenges and potential future perspectives of in situ bioprinting for cartilage applications.展开更多
Three-dimensional(3D)bioprinting is widely used in ophthalmic clinic,including in diagnosis,surgery,prosthetics,medications,drug development and delivery,and medical education.Articles published in 2011–2022 into bio...Three-dimensional(3D)bioprinting is widely used in ophthalmic clinic,including in diagnosis,surgery,prosthetics,medications,drug development and delivery,and medical education.Articles published in 2011–2022 into bioinks,printing technologies,and bioprinting applications in ophthalmology were reviewed and the strengths and limitations of bioprinting in ophthalmology highlighted.The review highlighted the trade-offs of printing technologies and bioinks in respect to,among others,material type cost,throughput,gelation technique,cell density,cell viability,resolution,and printing speed.There is already widespread ophthalmological application of bioprinting outside clinical settings,including in educational modelling,retinal imaging/visualization techniques and drug design/testing.In clinical settings,bioprinting has already found application in pre-operatory planning.Even so,the findings showed that even with its immense promise,actual translation to clinical applications remains distant,but relatively closer for the corneal(except stromal)tissues,epithelium,endothelium,and conjunctiva,than it was for the retina.This review similarly reflected on the critical on the technical,practical,ethical,and cost barrier to rapid progress of bioprinting in ophthalmology,including accessibility to the most sophisticated bioprinting technologies,choice,and suitability of bioinks,tissue viability and storage conditions.The extant research is encouraging,but more work is clearly required for the push towards clinical translation of research.展开更多
Biomanufacturing of tissues/organs in vitro is our big dream,driven by two needs:organ transplantation and accurate tissue models.Over the last decades,3D bioprinting has been widely applied in the construction of man...Biomanufacturing of tissues/organs in vitro is our big dream,driven by two needs:organ transplantation and accurate tissue models.Over the last decades,3D bioprinting has been widely applied in the construction of many tissues/organs such as skins,vessels,hearts,etc.,which can not only lay a foundation for the grand goal of organ replacement,but also be served as in vitro models committed to pharmacokinetics,drug screening and so on.As organs are so complicated,many bioprinting methods are exploited to figure out the challenges of different applications.So the question is how to choose the suitable bioprinting method?Herein,we systematically review the evolution,process and classification of 3D bioprinting with an emphasis on the fundamental printing principles and commercialized bioprinters.We summarize and classify extrusion-based,dropletbased,and photocuring-based bioprinting methods and give some advices for applications.Among them,coaxial and multi-material bioprinting are highlighted and basic principles of designing bioinks are also discussed.展开更多
The three-dimensional (3D)bioprinting technology has progressed tremendously over the past decade.By controlling the size, shape,and architecture of the bioprinted constructs,3D bioprinting allows for the fabrication ...The three-dimensional (3D)bioprinting technology has progressed tremendously over the past decade.By controlling the size, shape,and architecture of the bioprinted constructs,3D bioprinting allows for the fabrication of tissue/organ-like constructs with strong structural-functional similarity with their in vivo counterparts at high fidelity.The bioink,a blend of biomaterials and living cells possessing both high biocompatibility and printability,is a critical component of bioprinting.In particular, gelatin methacryloyl (GelMA)has shown its potential as a viable bioink material due to its suitable biocompatibility and readily tunable physicochemical properties.Current GelMA-based bioinks and relevant bioprinting strategies for GelMA bioprinting are briefly reviewed.展开更多
Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regen...Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies.However,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these impediments.In this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids.We also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue organization.To fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.展开更多
基金financial support from the National Natural Science Foundation of China(Nos.82202335,82230071,and 82172098)the Shanghai Sailing Program(No.22YF1414000).
文摘Three-dimensional(3D)bioprinting has revolutionized tissue engineering by enabling precise fabrication with bioinks.Among these techniques,digital light processing(DLP)stands out due to its exceptional resolution,speed,and biocompatibility.However,the progress of DLP is hindered by the limited availability of suitable bioinks.Currently,some studies involve simple mixing of different materials,resulting in bioinks that lack uniformity and photopolymerization characteristics.To address this challenge,we present an innovative one-pot synthesis method for bioinks based on methacrylated gelatin/alginate with hydroxyapatite(HAP).This approach offers significant advantages in terms of efficiency and uniformity.The synthesized bioinks demonstrate excellent printability,stability,and notably enhanced mechanical properties,facilitating optimal in vitro compatibility.Additionally,the HAP-hybrid bioinks printed scaffolds demonstrated impressive bone repair capabilities in vivo compared with pure organic bioinks.In conclusion,the Gel/Alg/HAP bioinks presented herein offer an innovative solution for DLP bioprinting within the field of bone tissue engineering.Their multifaceted advantages help overcome the limitations of restricted bioink choices,pushing forward the boundaries of bioprinting technology and contributing to the progress of regenerative medicine and tissue engineering.
基金This work was financially supported by the National Key Research and Development Program of China(No.2018YFA0703003)the National Natural Science Foundation of China(No.52125501)+1 种基金the Key Research Project of Shaanxi Province(Nos.2021LLRH-08,2020GXLH-Y-021,and 2021GXLH-Z-028)the Youth InnovationTeam of Shaanxi Universities and the Fundamental Research Funds for the Central Universities.
文摘Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications.However,it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resolution of conventional bioprinting techniques such as extrusion-and inkjet-based printing.Recently,an electrohydrodynamic(EHD)bioprinting strategy was reported for the precise deposition of well-organized cell-laden constructs with microscale filament size,whereas few studies have been devoted to developing bioinks that can be applied for EHD bioprinting and simultaneously support cell spreading.This study describes functionalized alginate-based bioinks for microscale EHD bioprinting using peptide grafting and fibrin incorporation,which leads to high cell viability(>90%)and cell spreading.The printed filaments can be further refined to as small as 30μm by incorporating polyoxyethylene and remained stable over one week when exposed to an aqueous environment.By utilizing the presented alginate-based bioinks,layer-specific cell alignment along the printing struts could be observed inside the EHD-printed microscale filaments,which allows fabricating living constructs with cell-scale filament resolution for guided cellular orientation.
基金supported by the Major Science and Technology Special Project of Henan Province,China(No.171100210600)the Program of China Scholarship Council(No.201807045057)+2 种基金the High Level Talent Internationalization Training Program of Henan Province,China(No.2019004)the Scientific and Technological Research Project of Henan Province,China(Nos.212102310854 and 222102310526)the Open Foundation of the State Key Laboratory of Fluid Power and Mechatronic Systems(No.GZKF-202105)。
文摘Cryobioprinting has tremendous potential to solve problems to do with lack of shelf availability in traditional bioprinting by combining extrusion bioprinting and cryopreservation.In order to ensure the viability of cells in the frozen state and avoid the possible toxicity of dimethyl sulfoxide(DMSO),DMSO-free bioink design is critical for achieving successful cryobioprinting.A nontoxic gelatin methacryloyl-based bioink used in cryobioprinting is composed of cryoprotective agents(CPAs)and a buffer solution.The selection and ratio of CPAs in the bioink directly affect the survival of cells in the frozen state.However,the development of universal and efficient cryoprotective bioinks requires extensive experimentation.We first compared two commonly used CPA formulations via experiments in this study.Results show that the effect of using ethylene glycol as the permeable CPA was 6.07%better than that of glycerol.Two datasets were obtained and four machinelearning models were established to predict experimental outcomes.The predictive powers of multiple linear regression(MLR),decision tree(DT),random forest(RF),and artificial neural network(ANN)approaches were compared,suggesting an order of ANN>RF>DT>MLR.The final selected ANN model was then applied to another dataset.Results reveal that this machine-learning method can accurately predict the effects of cryoprotective bioinks composed of different CPAs.Outcomes also suggest that the formulations presented here have universality.Our findings are likely to greatly accelerate research and development on the use of bioinks for cryobioprinting.
文摘Geometric and structural integrity often deteriorate in 3D printed cell-laden constructs over time due to cellular compaction and hydrogel shrinkage.This study introduces a new approach that synergizes the advantages of cell compatibility of biological hydrogels and mechanical stability of elastomeric polymers for structure fidelity maintenance upon stereolithography and extrusion 3D printing.Enabling this advance is the composite bioink,formulated by integrating elastomeric microparticles from poly(octamethylene maleate(anhydride)citrate)(POMaC)into biologically derived hydrogels(fibrin,gelatin methacryloyl(GelMA),and alginate).The composite bioink enhanced the elasticity and plasticity of the 3D printed constructs,effectively mitigating tissue compaction and swelling.It exhibited a low shear modulus and a rapid crosslinking time,along with a high ultimate compressive strength and resistance to deformation from cellular forces and physical handling;this was attributed to packing and stress dissipation of elastomeric particles,which was confirmed via mathematical modelling.Enhanced functional assembly and stability of human iPSC-derived cardiac tissues and primary vasculature proved the utility of the composite bioink in tissue engineering.In vivo implantation studies revealed that constructs containing POMaC particles exhibited improved resilience against host tissue stress,enhanced angiogenesis,and infiltration of pro-reparative macrophages.
基金the projects of National Natural Science Foundation of China(No.32301209)Key R&D Projects of Henan Province(Nos.231111312400 and 241111220400).
文摘Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructing complex biomimetic 3D architectures,which are currently restricted by the limited number of available bioinks with high printability,biomimicry,biocompatibility,and proper mechanical properties.Inspired by ubiquitous coacervation phenomena in biology,we present a unique mineral-biopolymer coacervation strategy that enables the hierarchical assembly of nanoclay and recombinant human collagen(RHC).This system was observed to undergo a coacervation transition(liquid‒liquid phase separation)spontaneously.The formed dense phase separated from its supernatant is the coacervate of clay-RHC-rich complexes,where polymer chains are sandwiched between silicate layers.Molecular dynamics simulation was first used to verify and explore the coacervation process.Then,the coacervates were demonstrated to be potential bioinks that exhibited excellent self-supporting and shear-thinning viscoelastic properties.Through extrusion-based printing,the versatility of the bioink was demonstrated by reconstructing the key features of several biological tissues,including multilayered lattice,vascular,nose,and ear-like structures,without the need for precrosslinking operations or support baths.Furthermore,the printed scaffolds were cytocompatible,elicited minimal inflammatory responses,and promoted bone regeneration in calvarial defects.
基金supported by the Natural Science Foundation of Zhejiang Province(No.TGY24E050004)the Ningbo Major Research and Development Plan Project(No.2024Z208)+2 种基金the National Natural Science Foundation of China(No.12202387)the Ningbo Health Technology Project(No.2023Y16)the Natural Science Foundation of Ningbo(No.2022J212).
文摘Osteosarcoma,an aggressive bone cancer found most often in children and adolescents,remains difficult to treat,and little improvement in survival rate has been observed over recent decades.The tumor microenvironment(TME),especially the extracellular matrix(ECM),is a critical factor determining cancer progression and chemotherapy resistance,yet traditional 2D models generally fail to replicate its properties.Recent development of 3D-bioprinted tumor models has facilitated improved simulation of the complexity of the TME,but specific models involving bioinks tailored to osteosarcoma remain underdeveloped.Gelatin methacryloyl(GelMA)is a common bioink that can rapidly gel and contains Arg-Gly-Asp(RGD)sequences.However,it lacks collagen’s triple-helix structure that is essential for ECM-cell communication.Hyaluronic acid(HA)is a macromolecule that is aberrantly expressed in osteosarcoma by mechanisms that remain largely unexplored.In this study,we developed a composite bioink containing GelMA,collagen,and HA,and applied it to 3D bioprint an in vitro osteosarcoma model.We found that HA significantly enhanced osteosarcoma cell proliferation and chemoresistance,as well as the expression of epithelial-mesenchymal transition and cancer stem cell markers.Furthermore,we found that HA abundance was positively correlated with hypoxia and angiogenesis signaling pathways,and this occurred mainly via upregulation of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)expression,thereby contributing to increased chemoresistance.Overall,our study provides a protocol for building in vitro realistic 3D-bioprinted models for studying osteosarcoma,highlights the role of HA in osteosarcoma progression,and offers a platform for developing new chemotherapy treatments.
文摘Bioinks are formulations of biomaterials and living cells, sometimes with growth factors or other biomolecules, while extrusion bioprinting is an emerging technique to apply or deposit these bioinks or biomaterial solutions to create three-dimensional (3D) constructs with architectures and mechanical/biological properties that mimic those of native human tissue or organs. Printed constructs have found wide applications in tissue engineering for repairing or treating tissue/organ injuries, as well as in vitro tissue modelling for testing or validating newly developed therapeutics and vaccines prior to their use in humans. Successful printing of constructs and their subsequent applications rely on the properties of the formulated bioinks, including the rheological, mechanical, and biological properties, as well as the printing process. This article critically reviews the latest developments in bioinks and biomaterial solutions for extrusion bioprinting, focusing on bioink synthesis and characterization, as well as the influence of bioink properties on the printing process. Key issues and challenges are also discussed along with recommendations for future research.
基金This work was supported by National Natural Science Foundation of China,Nos.32171353,52073314Guangdong Key Areas Research and Development Program,No.2020B1111150003+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2022A1515011388Science and Technology Projects of Guangzhou,No.202002020078。
文摘The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and protection.In this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner.After gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from GelMA.The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell viability.The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion.Furthermore,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials distribution.Overall,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.
基金This study was supported by the Beijing Natural Science Foundation(7204306)National Natural Science Foundation of China(82002056,81830064,81721092,32000969,81974019)+9 种基金National Key Research and Development Program of China(2018YFA0108700,2017YFA0105602)NSFC Projects of International Cooperation and Exchanges(81720108004)China Postdoctoral Science Foundation(2020M673672)Key Support Program for Growth Factor Research(SZYZ-TR-03)Chinese PLA General Hospital for Military Medical Innovation Research Project(CX19026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005)the Research Team Project of Natural Science Foundation of Guangdong Province of China(2017A030312007)the key program of guangzhou science research plan(201904020047)The Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423).
文摘Extrusion-based bioprinting (EBB) holds potential for regenerative medicine. However, the widely-used bioinks of EBB exhibit some limitations for skin regeneration, such as unsatisfactory bio-physical (i.e., mechanical, structural, biodegradable) properties and compromised cellular compatibilities, and the EBB-based bioinks with therapeutic effects targeting cutaneous wounds still remain largely undiscussed. In this review, the printability considerations for skin bioprinting were discussed. Then, current strategies for improving the physical properties of bioinks and for reinforcing bioinks in EBB approaches were introduced, respectively. Notably, we highlighted the applications and effects of current EBB-based bioinks on wound healing, wound scar formation, vasculari-zation and the regeneration of skin appendages (i.e., sweat glands and hair follicles) and discussed the challenges and future perspectives. This review aims to provide an overall view of the applications, challenges and promising solutions about the EBB-based bioinks for cutaneous wound healing and skin regeneration.
基金the financial support from the National Natural Science Foundation of China(No.32122046,12272032,82072082,32101102)the National Key R&D Program of China(No.2020YFC0122204,2018YFA0703100)+2 种基金the Youth Innovation Promotion Association of CAS[No.2019350]the Shenzhen Fundamental Research Foundation[No.JCYJ20210324115814040]the 111 Project(No.B13003).
文摘In the field of regenerative medicine,the importance of 3D bioprinting is self-evident and nonnegligible.However,3D bioprinting technology also requires bioink with excellent performance as support material to fabricate a multi-functional bioinspired scaffold.Collagen-based bioink is regarded as an ideal 3D bioprinting ink for its excellent biocompatibility,controllable printability and cell loading property.It is an important breakthrough in regenerative medicine with the progress of collagen-based bioink,which fabricates bioinspired scaffolds with different functions and is applied in different repair scenarios.This review summarizes the different applications of collagen-based bioink and classifies them as soft tissue and hard tissue according to the target region.The applications of target region in soft tissues include skin,cartilage,heart and blood vessels,while in hard tissues include femur,skull,teeth and spine.When the collagen-based bioink is applied in repairing soft tissue,the requirements of function are higher,while the mechanical properties must be further improved in repairing hard tissue.We further summarize the characteristics of collagen-based bioink and point out the most important properties that should be considered in different repair scenarios,which can provide reference for the preparation of bioinks with different functions.Finally,we point out the main challenges faced by collagen-based bioink and prospect the future research directions.
基金support from the National Natural Science Foundation of China (51873134 and 52303043)the Natural Science Foundation of Jiangsu Province of China (BK20211317)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (23KJB430031)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD),China National Textile and Apparel Council Key Laboratory for Silk Functional Materials and Technology,and the Opening Project of Key Laboratory of Jiangsu Province for Silk Engineering,Soochow University (KJS2168).
文摘In recent years,significant progress has been made in both three-dimensional(3D)printing technologies and the exploration of silk as an ink to produce biocompatible constructs.Combined with the unlimited design potential of 3D printing,silk can be processed into a broad range of functional materials and devices for various biomedical applications.The ability of silk to be processed into various materials,including solutions,hydrogels,particles,microspheres,and fibers,makes it an excellent candidate for adaptation to different 3D printing techniques.This review presents a didactic overview of the 3D printing of silk-based materials,major categories of printing techniques,and their prototyping mechanisms and structural features.In addition,we provide a roadmap for researchers aiming to incorporate silk printing into their own work by summarizing promising strategies from both technical and material aspects,to relate state-of-the-art silk-based material processing with fast-developing 3D printing technologies.Thus,our focus is on elucidating the techniques and strategies that advance the development of precise assembly strategies for silk-based materials.Precise printing(including high printing resolution,complex structure realization,and printing fidelity)is a prerequisite for the digital design capability of 3D printing technology and would definitely broaden the application era of silk,such as complex biomimetic tissue structures,vasculatures,and transdermal microneedles.
基金funded by the National Insti-tutes of Health(No.R01 AR074234)AHA collaborative award(No.944227)the Gillian Reny Stepping Strong Center for Trauma Inno-vation at Brigham and Women's Hospital.
文摘Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.
基金supported by National Natural Science Foundation of China(Grant Nos.U21A20394,52305314)Tsinghua-Toyota Joint Research Fund(Grant No.20223930093)National Key Research and Development Program of China(Grant No.2018YFA0703004).
文摘Three-dimensional(3D)bioprinting,which has been applied in tissue engineering and regenerative medicine,uses biomaterials,cells,and other essential components to manufacture organs and tissues with specific biological functions and complex structures.Over the past 30 years,researchers have developed new 3D bioprinting technologies with improved manufacturing capabilities and expanded applications.Chinese research teams contributed significantly to this process.In this paper,we first reviewed the development history and major milestones in 3D bioprinting,categorizing them into two main strategies:"biomaterial-based indirect assembly"and"living cell-based direct assembly".This review further delved into the technical principles,recent advancements,advantages,disadvantages,and applications of each type of bioprinting technology.Finally,the challenges and future directions of 3D bioprinting were summarized to guide future research in China and foster advancements in this dynamic field.
基金supported by the National Natural Science Foundation(No.32271468)Sichuan Science and Technology Program(No.2021JDTD0001)+2 种基金Natural Science Foundation of Sichuan Province(No.2022NSFSC1280)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH081)Sichuan Science and Technology Program(No.2021YFS0124)。
文摘Bioprinting is emerging as an advanced tool in tissue engineering.However,there is still a lack of bioinks able to form hydrogels with desirable bioactivities that support positive cell behaviors.In this study,modified plasma proteins capable of forming hydrogels with multiple biological functions are developed as bioinks for digital light processing(DLP)printing.The Plasma-MA(BM)was synthesized via a one-pot method through the reaction between the fresh frozen plasma and methacrylic anhydride.The methacry-lated levels were observed to influence the physical properties of BM hydrogels including mechanical properties,swelling,and degradation.The photo-crosslinked BM hydrogels can sustainedly release vascu-lar endothelial growth factor(VEGF)and exhibit positive biological effects on cell adhesion and prolifer-ation,and cell functionality such as tube formation of human umbilical vein endothelial cells(HUVECs),and neurite elongation of rat pheochromocytoma cells(PC12).Meanwhile,BM hydrogels can also induce cell infiltration,modulate immune response,and promote angiogenesis in vivo.Moreover,the plasma bioinks can be used to fabricate customized scaffolds with complex structures through a DLP printing process.These findings implicate that the modified plasma with growth factor release is a promising candidate for bioprinting in autologous and personalized tissue engineering.
文摘Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.
基金the funding provided by the United Kingdom(UK)Engineering and Physical Sciences Research Council(EPSRC)Doctoral Prize Fellowship(EP/R513131/1)。
文摘Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for efficacious cartilage repair,and long-term patient outcomes are not satisfying.Three-dimensional bioprinting has been used to fabricate biochemical and biophysical environments that aim to recapitulate the native microenvironment and promote tissue regeneration.However,conventional in vitro bioprinting has limitations due to the challenges associated with the fabrication and implantation of bioprinted constructs and their integration with the native cartilage tissue.In situ bioprinting is a novel strategy to directly deliver bioinks to the desired anatomical site and has the potential to overcome major shortcomings associated with conventional bioprinting.In this review,we focus on the new frontier of robotic-assisted in situ bioprinting surgical systems for cartilage regeneration.We outline existing clinical approaches and the utilization of robotic-assisted surgical systems.Handheld and robotic-assisted in situ bioprinting techniques including minimally invasive and non-invasive approaches are defined and presented.Finally,we discuss the challenges and potential future perspectives of in situ bioprinting for cartilage applications.
文摘Three-dimensional(3D)bioprinting is widely used in ophthalmic clinic,including in diagnosis,surgery,prosthetics,medications,drug development and delivery,and medical education.Articles published in 2011–2022 into bioinks,printing technologies,and bioprinting applications in ophthalmology were reviewed and the strengths and limitations of bioprinting in ophthalmology highlighted.The review highlighted the trade-offs of printing technologies and bioinks in respect to,among others,material type cost,throughput,gelation technique,cell density,cell viability,resolution,and printing speed.There is already widespread ophthalmological application of bioprinting outside clinical settings,including in educational modelling,retinal imaging/visualization techniques and drug design/testing.In clinical settings,bioprinting has already found application in pre-operatory planning.Even so,the findings showed that even with its immense promise,actual translation to clinical applications remains distant,but relatively closer for the corneal(except stromal)tissues,epithelium,endothelium,and conjunctiva,than it was for the retina.This review similarly reflected on the critical on the technical,practical,ethical,and cost barrier to rapid progress of bioprinting in ophthalmology,including accessibility to the most sophisticated bioprinting technologies,choice,and suitability of bioinks,tissue viability and storage conditions.The extant research is encouraging,but more work is clearly required for the push towards clinical translation of research.
基金sponsored by the National Natural Science Foundation of China(No.U1609207)。
文摘Biomanufacturing of tissues/organs in vitro is our big dream,driven by two needs:organ transplantation and accurate tissue models.Over the last decades,3D bioprinting has been widely applied in the construction of many tissues/organs such as skins,vessels,hearts,etc.,which can not only lay a foundation for the grand goal of organ replacement,but also be served as in vitro models committed to pharmacokinetics,drug screening and so on.As organs are so complicated,many bioprinting methods are exploited to figure out the challenges of different applications.So the question is how to choose the suitable bioprinting method?Herein,we systematically review the evolution,process and classification of 3D bioprinting with an emphasis on the fundamental printing principles and commercialized bioprinters.We summarize and classify extrusion-based,dropletbased,and photocuring-based bioprinting methods and give some advices for applications.Among them,coaxial and multi-material bioprinting are highlighted and basic principles of designing bioinks are also discussed.
基金the National Institutes of Health (K99CA201603,R21EB025270, R21EB026175)Doctoral New Investigator Grant from American Chemical Society Petroleum Research Fund (56840-DNI7).G.L. Y.acknowledges Natural and Science Foundation of Hubei Province (2014CFB778).
文摘The three-dimensional (3D)bioprinting technology has progressed tremendously over the past decade.By controlling the size, shape,and architecture of the bioprinted constructs,3D bioprinting allows for the fabrication of tissue/organ-like constructs with strong structural-functional similarity with their in vivo counterparts at high fidelity.The bioink,a blend of biomaterials and living cells possessing both high biocompatibility and printability,is a critical component of bioprinting.In particular, gelatin methacryloyl (GelMA)has shown its potential as a viable bioink material due to its suitable biocompatibility and readily tunable physicochemical properties.Current GelMA-based bioinks and relevant bioprinting strategies for GelMA bioprinting are briefly reviewed.
文摘Three-dimensional(3D)organoids derived from pluripotent or adult tissue stem cells seem to possess excellent potential for studying development and disease mechanisms alongside having a myriad of applications in regenerative therapies.However,lack of precise architectures and large-scale tissue sizes are some of the key limitations of current organoid technologies.3D bioprinting of organoids has recently emerged to address some of these impediments.In this review,we discuss 3D bioprinting with respect to the use of bioinks and bioprinting methods and highlight recent studies that have shown success in bioprinting of stem cells and organoids.We also summarize the use of several vascularization strategies for the bioprinted organoids,that are critical for a complex tissue organization.To fully realize the translational applications of organoids in disease modeling and regenerative medicine,these areas in 3D bioprinting need to be appropriately harnessed and channelized.
