The constraints of traditional 3D bioprinting are overcome by 4D bioprinting integrating with adaptable materials over time,resulting in dynamic,compliant,and functional biological structures.This innovative approach ...The constraints of traditional 3D bioprinting are overcome by 4D bioprinting integrating with adaptable materials over time,resulting in dynamic,compliant,and functional biological structures.This innovative approach to bioprinting holds great promise for tissue engineering,regenerative medicine,and advanced drug delivery systems.4D bioprinting is a technology that allows for the extension of 3D bioprinting technology by making predesigned structures change after they are fabricated using smart materials that can alter their characteristics via stimulus,leading to transformation in healthcare,which is able to provide precise personalized effective medical treatment without any side effects.This review article concentrates on some recent developments and applications in the field of 4D bioprinting,which can pave the way for groundbreaking advancements in biomedical sciences.4D printing is a new chapter in bioprinting that introduces dynamism and functional living biological structures.Therefore,smart materials and sophisticated printing techniques can eliminate the challenges associated with printing complex organs and tissues.However,the problems with this process are biocompatibility,immunogenicity,and scalability,which need to be addressed.Moreover,numerous obstacles have been encountered during its widespread adoption in clinical practice.Therefore,4D bioprinting requires improvements in future material science innovations and further development in printers and manufacturing techniques to unlock its potential for better patient care and outcomes.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
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
Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal sympto...Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.展开更多
Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of s...Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of several layers including the epidermis,basement membrane(BM),and dermis.However,the unique undulating structure of basement membranes(i.e.rete ridges)and the function of BM have not been extensively studied in the fabrication of engineered skin substitutes.In this study,a novel engineered skin substitute incorporating an artificially designed rete ridge(i.e.mogul-shape)was developed using bioprinting and bioinks prepared using collagen and fibrinogen.To mimic the structure of the rete ridges of skin tissue,we developed a modified bioprinting technique,controlling rheological property of bioink to create a mogul-shaped layer.In vitro cellular activities,including the expression of specific genes(those encoding vimentin,laminin-5,collagen IV,and cytokeratins),demonstrated that the engineered skin substitute exhibited more potent cellular responses than the normally bioprinted control owing to the favorable biophysical BM structure and the bioink microenvironment.Additionally,the feasibility of utilizing the bioprinted skin-structure was evaluated in a mouse model,and in vivo results demonstrated that the bioprinted skin substitutes effectively promoted wound healing capabilities.Based on these results,we suggest that bioprinted skin tissues and the bioprinting technique for mimicking rete ridges can be used not only as potential lab-chip models for testing cosmetic materials and drugs,but also as complex physiological models for understanding human skin.展开更多
Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidel...Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidelines has limited their optimal engineering,as the factors influencing their mechanical performance and printability remain largely unexamined.In this study,we developed GC hydrogels by integrating microgels with interstitial matrices of photocrosslinkable gelatin methacrylate(GelMA).We utilized confocal microscopy and nanoindentation analyses to investigate the spatial distribution and mechanical behavior of these hydrogels.Our findings indicate that the mechanical and rheological properties of GC hydrogels can be precisely tailored by adjusting the volume fraction and size of the microgels.Furthermore,hydrogen bonds were identified as significant contributors to compressive performance,although they had minimal effect on cyclic mechanical behavior.Compared to bulk GelMA hydrogels,GC hydrogels demonstrated enhanced printability and remarkable superelasticity.As a proof of concept,we illustrated their dual printability in embedded printing to create prosthetic liver models for preoperative planning.This study provides valuable insights into the design and optimization of GC hydrogels for advanced biomedical applications.展开更多
Three-dimensional(3D)bioprinting provides a rapid and efficient method for fabricating customized bioprinted tissues that replicate the complex architecture of native tissues.However,in 3D bioprinting,the need for den...Three-dimensional(3D)bioprinting provides a rapid and efficient method for fabricating customized bioprinted tissues that replicate the complex architecture of native tissues.However,in 3D bioprinting,the need for dense biomaterial networks to ensure mechanical strength and structural fidelity often restricts the spreading,migration,and proliferation of encapsulated cells,as well as the transport of materials.This review summarizes effective strategies for manufacturing microporous bioprinted tissues via 3D bioprinting.The term“microporous”refers to interconnected,micrometer-sized pore-like structures within the internal materials of bioprinted tissues,including the microstructure of a single extruded fiber in extrusion printing.This differs from the macroscopic pore structure formed between fibers composed of print tracks or computer-aided design presets.These micropores play a crucial role in advancing biomanufacturing and 3D bioprinting by providing space for cell adhesion and proliferation while facilitating the timely transport of nutrients and metabolic waste essential for cell growth.Additionally,microporous bioprinted tissues offer the mechanical support needed for cell seeding and serve as sites for extracellular matrix deposition.As microporous 3D bioprinting continues to advance,it has the potential to address unresolved challenges in fields such as organ transplantation,tissue regeneration,and tissue replacement.展开更多
Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex ...Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex 3D structures.By adjusting light exposure,it becomes possible to control the mechanical properties of the structure,a critical factor in modulating cell activities.To better mimic cell densities in real tissues,recent progress has been made in achieving high-cell-density(HCD)printing with high resolution.However,regulating the stiffness in HCD constructs remains challenging.The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption,reflection,and scattering.Here,we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds.Using comprehensive mechanical testing data from 3D bioprinted samples,the model was trained to deliver accurate predictions.To address the demand of working with precious and costly cell types,we employed various methods to ensure the generalizability of the model,even with limited datasets.We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data.The chosen method outperformed many other machine learning techniques,offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds.This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.展开更多
This comprehensive review explores the multifaceted landscape of skin bioprinting,revolutionizing dermatological research.The applications of skin bioprinting utilizing techniques like extrusion-,droplet-,laser-and li...This comprehensive review explores the multifaceted landscape of skin bioprinting,revolutionizing dermatological research.The applications of skin bioprinting utilizing techniques like extrusion-,droplet-,laser-and light-based methods,with specialized bioinks for skin biofabrication have been critically reviewed along with the intricate aspects of bioprinting hair follicles,sweat glands,and achieving skin pigmentation.Challenges remain with the need for vascularization,safety concerns,and the integration of automated processes for effective clinical translation.The review further investigates the incorporation of biosensor technologies,emphasizing their role in monitoring and enhancing the wound healing process.While highlighting the remarkable progress in the field,critical limitations and concerns are critically examined to provide a balanced perspective.This synthesis aims to guide scientists,engineers,and healthcare providers,fostering a deeper understanding of the current state,challenges,and future directions in skin bioprinting for transformative applications in tissue engineering and regenerative medicine.展开更多
Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to ther...Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to therapy resistance and metastasis.Advances in three-dimensional(3D)bioprinting have ushered in a new era of precision medicine by enabling the recreation of complex tumor mi-croenvironments.This review highlights the transformative potential of 3D bioprinting technology in modelling prostate cancer stem cells(PCSCs)to identify therapeutic vulnerabilities and develop targeted treatments.By integrating bioinks with PCSCs and their niche components,3D bioprinting offers a robust platform to investigate the molecular and cellular mechanisms underlying PCa progression and resistance.Furthermore,it allows high-throughput drug scree-ning,cellular cross talks,facilitating the discovery of novel interventions aimed at eradicating CSCs while preserving healthy tissue.The review also discusses the challenges of scalability,bioink optimization,and clinical translation,alongside emerging technologies such as organ-on-chip systems and bioprinted metastatic models.This review underscores the promise of bioprinting as a disruptive in-novation in cancer care,capable of redefining therapeutic approaches and offering hope for better patient outcomes in PCa.展开更多
Objective and Impact Statement:The microspheres were widely utilized in the field of life sciences,and we have developed an innovative microelectromechanical system(MEMS)-based bioprinting technology(MBT)system for th...Objective and Impact Statement:The microspheres were widely utilized in the field of life sciences,and we have developed an innovative microelectromechanical system(MEMS)-based bioprinting technology(MBT)system for the preparation of the microspheres.The microspheres can be automatically and high-throughput produced with this cutting-edge system.Introduction and Methods:This paper mainly introduced a novel,efficient,and cost-effective approach for the microsphere fabrication with the MBT system.In this work,the whole microsphere production equipment was built and the optimal conditions(like concentration,drying temperature,frequency,and voltage)for generating uniform hydroxypropyl cellulose-cyclosporine A(HPC-CsA)and poly-l-lactic acid(PLLA)microspheres were explored.Results:Results demonstrated that the optimal uniformity of HPC-CsA microspheres was achieved at 2%(w/v)HPC-CsA mixture,45°C(drying temperature),1,000 Hz(frequency),and 25 V(voltage amplitude).CsA microspheres[coefficient of variation(CV):~9%]are successfully synthesized,and the drug encapsulation rate was 84.8%.The methodology was further used to produce PLLA microspheres with a diameter of~2.55μm,and the best CV value achieved 6.84%.Conclusion:This investigation fully highlighted the integration of MEMS and bioprinting as a promising tool for the microsphere fabrication,and this MBT system had huge potential applications in pharmaceutical formulations and medical aesthetics.展开更多
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t...Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.展开更多
Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional ...Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.展开更多
Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been ...Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been employed in various advanced industrial areas.The development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative bioproducts.However,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and biodegradability.In this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D printing.Therefore,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced applications.Israel,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting field.This review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue engineering.This paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide self-assembly.Undoubtedly,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.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
Jetting-based bioprinting facilitates contactless drop-on-demand deposition of subnanoliter droplets at well-defined positions to control the spatial arrangement of cells,growth factors,drugs,and biomaterials in a hig...Jetting-based bioprinting facilitates contactless drop-on-demand deposition of subnanoliter droplets at well-defined positions to control the spatial arrangement of cells,growth factors,drugs,and biomaterials in a highly automated layer-by-layer fabrication approach.Due to its immense versatility,jetting-based bioprinting has been used for various applications,including tissue engineering and regenerative medicine,wound healing,and drug development.A lack of in-depth understanding exists in the processes that occur during jetting-based bioprinting.This review paper will comprehensively discuss the physical considerations for bioinks and printing conditions used in jetting-based bioprinting.We first present an overview of different jetting-based bioprinting techniques such as inkjet bioprinting,laser-induced forward transfer bioprinting,electrohydrodynamic jet bioprinting,acoustic bioprinting and microvalve bioprinting.Next,we provide an in-depth discussion of various considerations for bioink formulation relating to cell deposition,print chamber design,droplet formation and droplet impact.Finally,we highlight recent accomplishments in jetting-based bioprinting.We present the advantages and challenges of each method,discuss considerations relating to cell viability and protein stability,and conclude by providing insights into future directions of jetting-based bioprinting.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
Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,ce...Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,cell spheres are threedimensional(3D)structures that can naturally form complex cell–cell and cell–matrix interactions.This structure is close to the natural environment of cells in living organisms.In addition to being used in disease modeling and drug screening,spheroids have significant potential in tissue regeneration.The 3D bioprinting is an advanced biofabrication technique.It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures.Although 3D bioprinting is efficient,the time required for cells to develop into complex tissue structures can be lengthy.The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density.Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine.This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks.Finally,we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.展开更多
Organ damage or failure arising from injury,disease,and aging poses challenges due to the body’s limited regenerative capabilities.Organ transplantation presents the issues of donor shortages and immune rejection ris...Organ damage or failure arising from injury,disease,and aging poses challenges due to the body’s limited regenerative capabilities.Organ transplantation presents the issues of donor shortages and immune rejection risks,necessitating innovative solutions.The three-dimensional(3D)bioprinting of organs on demand offers promise in tissue engineering and regenerative medicine.In this review,we explore the state-of-the-art bioprinting technologies,with a focus on bioink and cell type selections.We follow with discussions on advances in the bioprinting of solid organs,such as the heart,liver,kidney,and pancreas,highlighting the importance of vascularization and cell integration.Finally,we provide insights into key challenges and future directions in the context of the clinical translation of bioprinted organs and their large-scale production.展开更多
基金the Scientific and Technological Research Council of Turkey (TÜBİTAK) for their support through the TÜBİTAK 2211-A National PhD Fellowship Program
文摘The constraints of traditional 3D bioprinting are overcome by 4D bioprinting integrating with adaptable materials over time,resulting in dynamic,compliant,and functional biological structures.This innovative approach to bioprinting holds great promise for tissue engineering,regenerative medicine,and advanced drug delivery systems.4D bioprinting is a technology that allows for the extension of 3D bioprinting technology by making predesigned structures change after they are fabricated using smart materials that can alter their characteristics via stimulus,leading to transformation in healthcare,which is able to provide precise personalized effective medical treatment without any side effects.This review article concentrates on some recent developments and applications in the field of 4D bioprinting,which can pave the way for groundbreaking advancements in biomedical sciences.4D printing is a new chapter in bioprinting that introduces dynamism and functional living biological structures.Therefore,smart materials and sophisticated printing techniques can eliminate the challenges associated with printing complex organs and tissues.However,the problems with this process are biocompatibility,immunogenicity,and scalability,which need to be addressed.Moreover,numerous obstacles have been encountered during its widespread adoption in clinical practice.Therefore,4D bioprinting requires improvements in future material science innovations and further development in printers and manufacturing techniques to unlock its potential for better patient care and outcomes.
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 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.
基金Open access funding provided by Manipal Academy of Higher Education,Manipal.
文摘Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.
基金supported by the‘Korea National Institute of Health’(KNIH)research project(Project No.2022ER130502)the National Research Foundation of Korea(NRF)Grant funded by the Korea Government(MSIT)(No.2021R1A2C20060331222182102840102)。
文摘Bioprinting is a widely used technique for creating three-dimensional,complex,and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues.The skin is composed of several layers including the epidermis,basement membrane(BM),and dermis.However,the unique undulating structure of basement membranes(i.e.rete ridges)and the function of BM have not been extensively studied in the fabrication of engineered skin substitutes.In this study,a novel engineered skin substitute incorporating an artificially designed rete ridge(i.e.mogul-shape)was developed using bioprinting and bioinks prepared using collagen and fibrinogen.To mimic the structure of the rete ridges of skin tissue,we developed a modified bioprinting technique,controlling rheological property of bioink to create a mogul-shaped layer.In vitro cellular activities,including the expression of specific genes(those encoding vimentin,laminin-5,collagen IV,and cytokeratins),demonstrated that the engineered skin substitute exhibited more potent cellular responses than the normally bioprinted control owing to the favorable biophysical BM structure and the bioink microenvironment.Additionally,the feasibility of utilizing the bioprinted skin-structure was evaluated in a mouse model,and in vivo results demonstrated that the bioprinted skin substitutes effectively promoted wound healing capabilities.Based on these results,we suggest that bioprinted skin tissues and the bioprinting technique for mimicking rete ridges can be used not only as potential lab-chip models for testing cosmetic materials and drugs,but also as complex physiological models for understanding human skin.
基金support from the National Natural Science Foundation of China(Nos.U21A20394 and 52305314)the Beijing Natural Science Foundation(Nos.7252285 and L246001)the National Key Research and Development Program of China(No.2023YFB4605800)。
文摘Granular composite(GC)hydrogels have attracted considerable interest in biomedical applications due to their versatile printability and exceptional mechanical properties.However,the lack of comprehensive design guidelines has limited their optimal engineering,as the factors influencing their mechanical performance and printability remain largely unexamined.In this study,we developed GC hydrogels by integrating microgels with interstitial matrices of photocrosslinkable gelatin methacrylate(GelMA).We utilized confocal microscopy and nanoindentation analyses to investigate the spatial distribution and mechanical behavior of these hydrogels.Our findings indicate that the mechanical and rheological properties of GC hydrogels can be precisely tailored by adjusting the volume fraction and size of the microgels.Furthermore,hydrogen bonds were identified as significant contributors to compressive performance,although they had minimal effect on cyclic mechanical behavior.Compared to bulk GelMA hydrogels,GC hydrogels demonstrated enhanced printability and remarkable superelasticity.As a proof of concept,we illustrated their dual printability in embedded printing to create prosthetic liver models for preoperative planning.This study provides valuable insights into the design and optimization of GC hydrogels for advanced biomedical applications.
基金supported by the National Natural Science Foundation of China(Nos.82302786 and 82172394)the China Postdoctoral Science Foundation(Nos.BX20230245 and 2023M742478)+4 种基金the Sichuan Science and Technology Program(No.2023YFH0068)the Sichuan Province Innovative Talent Funding Project for Postdoctoral Fellows(No.BX202203)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(No.JCXK2226)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD23033)the Postdoctoral Research Fund of West China Hospital,Sichuan University(No.2023HXBH012).
文摘Three-dimensional(3D)bioprinting provides a rapid and efficient method for fabricating customized bioprinted tissues that replicate the complex architecture of native tissues.However,in 3D bioprinting,the need for dense biomaterial networks to ensure mechanical strength and structural fidelity often restricts the spreading,migration,and proliferation of encapsulated cells,as well as the transport of materials.This review summarizes effective strategies for manufacturing microporous bioprinted tissues via 3D bioprinting.The term“microporous”refers to interconnected,micrometer-sized pore-like structures within the internal materials of bioprinted tissues,including the microstructure of a single extruded fiber in extrusion printing.This differs from the macroscopic pore structure formed between fibers composed of print tracks or computer-aided design presets.These micropores play a crucial role in advancing biomanufacturing and 3D bioprinting by providing space for cell adhesion and proliferation while facilitating the timely transport of nutrients and metabolic waste essential for cell growth.Additionally,microporous bioprinted tissues offer the mechanical support needed for cell seeding and serve as sites for extracellular matrix deposition.As microporous 3D bioprinting continues to advance,it has the potential to address unresolved challenges in fields such as organ transplantation,tissue regeneration,and tissue replacement.
基金supported in part by the National Institutes of Health(Nos.R01HD112026 and R21ES034455)National Science Foundation(NSF,Nos.2135720 and 2223669)performed at San Diego Nanotechnology Infrastructure(SDNI)of UCSD,a member of the National Nanotechnology Coordinated Infrastructure(NNCI),which is supported by NSF(Grant No.ECCS-2025752).
文摘Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex 3D structures.By adjusting light exposure,it becomes possible to control the mechanical properties of the structure,a critical factor in modulating cell activities.To better mimic cell densities in real tissues,recent progress has been made in achieving high-cell-density(HCD)printing with high resolution.However,regulating the stiffness in HCD constructs remains challenging.The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption,reflection,and scattering.Here,we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds.Using comprehensive mechanical testing data from 3D bioprinted samples,the model was trained to deliver accurate predictions.To address the demand of working with precious and costly cell types,we employed various methods to ensure the generalizability of the model,even with limited datasets.We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data.The chosen method outperformed many other machine learning techniques,offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds.This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.
基金supported by National Institutes of Health Award(Nos.R01DE028614(I T O)and R21AR082668(I T O)),and 2236 CoCirculation2 of TUBITAK award(No.121C359(I T O))supported by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense,in the amount of($1986275)through the Peer Reviewed Medical Research Program under Award Number(No.HT9425-23-1-0487)。
文摘This comprehensive review explores the multifaceted landscape of skin bioprinting,revolutionizing dermatological research.The applications of skin bioprinting utilizing techniques like extrusion-,droplet-,laser-and light-based methods,with specialized bioinks for skin biofabrication have been critically reviewed along with the intricate aspects of bioprinting hair follicles,sweat glands,and achieving skin pigmentation.Challenges remain with the need for vascularization,safety concerns,and the integration of automated processes for effective clinical translation.The review further investigates the incorporation of biosensor technologies,emphasizing their role in monitoring and enhancing the wound healing process.While highlighting the remarkable progress in the field,critical limitations and concerns are critically examined to provide a balanced perspective.This synthesis aims to guide scientists,engineers,and healthcare providers,fostering a deeper understanding of the current state,challenges,and future directions in skin bioprinting for transformative applications in tissue engineering and regenerative medicine.
基金Supported by GSBTM,DST Government of Gujarat for Financial Support to the Prostate Cancer Research Project at GSFC University,Vadodara,No.GSBTM/RSS/E-FILE/30/2024/0021/04306791.
文摘Prostate cancer(PCa),one of the leading causes of cancer-related mortality in men worldwide,presents significant challenges due to its heterogeneity and the presence of cancer stem cells(CSCs),which contribute to therapy resistance and metastasis.Advances in three-dimensional(3D)bioprinting have ushered in a new era of precision medicine by enabling the recreation of complex tumor mi-croenvironments.This review highlights the transformative potential of 3D bioprinting technology in modelling prostate cancer stem cells(PCSCs)to identify therapeutic vulnerabilities and develop targeted treatments.By integrating bioinks with PCSCs and their niche components,3D bioprinting offers a robust platform to investigate the molecular and cellular mechanisms underlying PCa progression and resistance.Furthermore,it allows high-throughput drug scree-ning,cellular cross talks,facilitating the discovery of novel interventions aimed at eradicating CSCs while preserving healthy tissue.The review also discusses the challenges of scalability,bioink optimization,and clinical translation,alongside emerging technologies such as organ-on-chip systems and bioprinted metastatic models.This review underscores the promise of bioprinting as a disruptive in-novation in cancer care,capable of redefining therapeutic approaches and offering hope for better patient outcomes in PCa.
基金sponsored by Shanghai Pujiang Program(23PJ1423400)Shanghai Rising-Star Program(23QB1405100)National Key Research and Development Program of China(2019YFA0707004 and SQ2021YFF0700202).
文摘Objective and Impact Statement:The microspheres were widely utilized in the field of life sciences,and we have developed an innovative microelectromechanical system(MEMS)-based bioprinting technology(MBT)system for the preparation of the microspheres.The microspheres can be automatically and high-throughput produced with this cutting-edge system.Introduction and Methods:This paper mainly introduced a novel,efficient,and cost-effective approach for the microsphere fabrication with the MBT system.In this work,the whole microsphere production equipment was built and the optimal conditions(like concentration,drying temperature,frequency,and voltage)for generating uniform hydroxypropyl cellulose-cyclosporine A(HPC-CsA)and poly-l-lactic acid(PLLA)microspheres were explored.Results:Results demonstrated that the optimal uniformity of HPC-CsA microspheres was achieved at 2%(w/v)HPC-CsA mixture,45°C(drying temperature),1,000 Hz(frequency),and 25 V(voltage amplitude).CsA microspheres[coefficient of variation(CV):~9%]are successfully synthesized,and the drug encapsulation rate was 84.8%.The methodology was further used to produce PLLA microspheres with a diameter of~2.55μm,and the best CV value achieved 6.84%.Conclusion:This investigation fully highlighted the integration of MEMS and bioprinting as a promising tool for the microsphere fabrication,and this MBT system had huge potential applications in pharmaceutical formulations and medical aesthetics.
基金supported by the National Natural Science Foundation of China,No.82171380(to CD)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program,No.202110304098Y(to DJ)。
文摘Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.
基金partially supported by the National Natural Science Foundation of China(No.82473256)the Jiangxi Provincial Natural Science Foundation,China(No.20242BAB25521)+7 种基金Ganpo Promising Talents Supporting Plan—Talent Development Project of Leading Academic and Technological Researchers in Key Disciplines(No.20243BCE51060)the Anhui Province Higher Education Scientific Research Project,China(No.2024AH050818)the Anhui Provincial Natural Science Foundation,China(No.2208085MH251)the Fundamental Research Funds for the Anhui Medical University,China(No.2021xkj131)the Research Fund of Anhui Institute of Translational Medicine,China(No.2023zhyx-C19)the Health Research Program of Anhui,China(No.AHWJ2023A30007)the Anhui Provincial Department of Education,Provincial Quality Engineering Project for Higher Education(Nos.2022jyxm761 and 2023jyxm1106)the Basic and Clinical Cooperative Research and Promotion Program of the Anhui Medical University,China(No.2022xkj T024)。
文摘Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.
基金supported by the National Key R&D Program of China within the China-Israel Cooperative Scientific Research(No.2022YFE0100800)(Israeli No.3-18130)the National Natural Science Foundation of China(Nos.52175551,22072181)+1 种基金the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Province,China(No.2022R01001)the Zhejiang University Global Partnership Fund and Open Foundation of the State Key Laboratory of Fluid Power and Mechatronic Systems(No.GZKF-202224).
文摘Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical printing.It has also been employed in various advanced industrial areas.The development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative bioproducts.However,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and biodegradability.In this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D printing.Therefore,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced applications.Israel,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting field.This review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue engineering.This paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide self-assembly.Undoubtedly,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.
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support from NTU Presidential Postdoctoral Fellowship.
文摘Jetting-based bioprinting facilitates contactless drop-on-demand deposition of subnanoliter droplets at well-defined positions to control the spatial arrangement of cells,growth factors,drugs,and biomaterials in a highly automated layer-by-layer fabrication approach.Due to its immense versatility,jetting-based bioprinting has been used for various applications,including tissue engineering and regenerative medicine,wound healing,and drug development.A lack of in-depth understanding exists in the processes that occur during jetting-based bioprinting.This review paper will comprehensively discuss the physical considerations for bioinks and printing conditions used in jetting-based bioprinting.We first present an overview of different jetting-based bioprinting techniques such as inkjet bioprinting,laser-induced forward transfer bioprinting,electrohydrodynamic jet bioprinting,acoustic bioprinting and microvalve bioprinting.Next,we provide an in-depth discussion of various considerations for bioink formulation relating to cell deposition,print chamber design,droplet formation and droplet impact.Finally,we highlight recent accomplishments in jetting-based bioprinting.We present the advantages and challenges of each method,discuss considerations relating to cell viability and protein stability,and conclude by providing insights into future directions of jetting-based bioprinting.
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.
基金supported by the National Natural Science Foundation of China(Nos.61973206,61703265,61803250,and 61933008)the Shanghai Science and Technology Committee Rising-Star Program(No.19QA1403700)the National Center for Translational Medicine(Shanghai)SHU Branch.
文摘Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,cell spheres are threedimensional(3D)structures that can naturally form complex cell–cell and cell–matrix interactions.This structure is close to the natural environment of cells in living organisms.In addition to being used in disease modeling and drug screening,spheroids have significant potential in tissue regeneration.The 3D bioprinting is an advanced biofabrication technique.It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures.Although 3D bioprinting is efficient,the time required for cells to develop into complex tissue structures can be lengthy.The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density.Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine.This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks.Finally,we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.
基金supported by the National Natural Science Foundation of China(82372403)the Shenzhen Science and Technology Program(ZDSYS20220606100606013)+5 种基金the Shenzhen Institute of Synthetic Biology Scientific Research Program(DWKF20190010 and JCHZ20200005)the Shenzhen Science and Technology Major Project(KJZD20230923114302006)the National Institute of Dental and Craniofacial Research Award(R01DE028614)the National Institute of Biomedical Imaging and Bioengineering Award(R01EB034566)the National Institute of Allergy and the Infectious Diseases Award(U19AI142733)the 2236 CoCirculation2 of TUBITAK award(121C359).
文摘Organ damage or failure arising from injury,disease,and aging poses challenges due to the body’s limited regenerative capabilities.Organ transplantation presents the issues of donor shortages and immune rejection risks,necessitating innovative solutions.The three-dimensional(3D)bioprinting of organs on demand offers promise in tissue engineering and regenerative medicine.In this review,we explore the state-of-the-art bioprinting technologies,with a focus on bioink and cell type selections.We follow with discussions on advances in the bioprinting of solid organs,such as the heart,liver,kidney,and pancreas,highlighting the importance of vascularization and cell integration.Finally,we provide insights into key challenges and future directions in the context of the clinical translation of bioprinted organs and their large-scale production.
