Additive manufacturing,or 3D printing,has transformed tissue engineering by enabling the creation of intricate scaffolds and cell scaffold constructs that closely mimic organic tissues.This technique provides a founda...Additive manufacturing,or 3D printing,has transformed tissue engineering by enabling the creation of intricate scaffolds and cell scaffold constructs that closely mimic organic tissues.This technique provides a foundation for creating structures that promote cell proliferation and tissue growth.The shift from 3D to 4D printing has introduced dynamic and time-responsive scaffolds that enhance the capabilities of tissue engineering by allowing constructs to modify their shape or function in response to environmental stimuli.These advancements are crucial for formulating adaptable treatments for human tissue regeneration.Bioprinting,a branch of 3D and 4D printing,incorporates living cells into printed constructs,resulting in cell-infused entities that harmoniously integrate with the human body.This method has considerable promise for producing live tissues;yet,both 3D/4D printing and bioprinting have technological limitations concerning precision,scalability,and functional intricacy.In response to these challenges,5D printing has emerged as a conceptual innovation beyond traditional dimensions.In 5D bioprinting,information serves as the fifth dimension and is embedded into printed objects along the dimensions of space and time.This supplementary information enables 5D-printed structures to interact more dynamically with their surroundings.Upon activation,this embedded information can alter ambient conditions or trigger functional responses inside printed objects,thereby enhancing the adaptability and integration with biological systems.This article presents a comprehensive analysis of 4D bioprinting methodologies in tissue engineering,followed by an exploration of the potential of 5D printing.5D bioprinting incorporates spatial,temporal,and informational dimensions,fostering innovative prospects in biomedical applications,and advancing the creation of intelligent scaffolds and adaptive biomaterials that can transform regenerative medicine and personalized healthcare.展开更多
With the rapid advancements in biomedical engineering,bioprinting has emerged as a pivotal solution to address the shortage of organ transplants and advance disease model research.The evolution of bioprinting has prog...With the rapid advancements in biomedical engineering,bioprinting has emerged as a pivotal solution to address the shortage of organ transplants and advance disease model research.The evolution of bioprinting has progressed from the fabrication of simple models(1.0)to the fabrication of permanent implants(2.0),tissue engineering scaffolds(3.0),and complex biostructures utilizing living cells(4.0).Nevertheless,significant challenges remain,particularly in accurately replicating the structure and function of host tissues,selecting appropriate materials,and optimizing printing parameters.The integration of artificial intelligence(AI),especially machine learning,provides promising novel opportunities in bioprinting(5.0).This review systematically summarizes the current applications of AI in bioprinting,discussing both construction strategies and application scenarios.It also explores the potential of AI to improve bioprinting in the preparation of complex functional tissues and in situ tissue repair.Overall,the synergy between AI and bioprinting is poised to drive the development of personalized medicine,facilitate high-throughput preparation of in vitro models,and provide robust tools for regenerative medicine and precision healthcare.展开更多
Bioprinting provides an unparalleled tool for engineering living tissue constructs that mimic the structural organization of native skeletal muscles.However,it remains a challenge for existing bioprinting strategies t...Bioprinting provides an unparalleled tool for engineering living tissue constructs that mimic the structural organization of native skeletal muscles.However,it remains a challenge for existing bioprinting strategies to recapitulate the highly aligned cellular architectures inside skeletal muscles,primarily due to low printing resolution and limited capability for in situ microenvironmental regulation.Here,we propose to employ the electrical force during the electrohydrodynamic(EHD)bioprinting process to induce the in situ orientation of cell-laden fibrin-alginate hydrogel,which provides nanostructural guidance to the encapsulated cells for the formation of highly aligned skeletal muscle constructs.It was observed that the randomly distributed fibrin protofibril aggregates gradually elongated into uniformly aligned nanofibers at the Taylor cone stage as the applied voltage increased to 3 kV.The oriented fibrin nanofibers further direct in situ cellular alignment along the EHD bioprinting trajectory,facilitating the freeform fabrication of parallelly or circumferentially aligned muscle tissue constructs in vitro.The addition of conductive polymers into the fibrin-alginate hydrogel endows the EHD-bioprinted living constructs with muscle-specific conductivity and cellular organization,which promote myotube differentiation and maturation.The resultant aligned and conductive muscle constructs promoted in situ muscle regeneration and restored lost muscle functions at the defect regions in vivo.The presented EHD bioprinting strategy for fibrin-alginate hydrogel provides a versatile and simple platform to freely fabricate conductive,living tissue constructs with designer cellular alignments.展开更多
Objective:To investigate the repair of spinal cord injury(SCI)in rats using 3D bioprinted decellularized extracellular matrix(dECM)hydrogel,neural stem cells(NSCs),and TGF-β1 monoclonal antibody.Methods:The spinal co...Objective:To investigate the repair of spinal cord injury(SCI)in rats using 3D bioprinted decellularized extracellular matrix(dECM)hydrogel,neural stem cells(NSCs),and TGF-β1 monoclonal antibody.Methods:The spinal cord-derived dECM hydrogel(SC-dECM-gel)was optimized for 3D printing.Rheological tests established a 3%concentration as optimal.In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation.A rat SCI model was treated with the printed gel,and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials.Results:The 3%SC-dECM-gel showed superior rheological properties.TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro.In vivo,the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration.Conclusion:3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats,offering a promising approach for SCI treatment.展开更多
Tomographic volumetric bioprinting(TVBP)is an emerging transformative technology in bio-manufacturing,distinguished by two exceptional capabilities:ultrafast fabrication(centimeter-scale constructs within tens of seco...Tomographic volumetric bioprinting(TVBP)is an emerging transformative technology in bio-manufacturing,distinguished by two exceptional capabilities:ultrafast fabrication(centimeter-scale constructs within tens of seconds)and unique compatibility with ultra-soft bioinks(<102Pa).Despite its potential,TVBP remains in its infancy because of significant hurdles.These include the need to adapt conventional photocurable bioinks to TVBP’s unique photopolymerization requirements and achieve sufficient resolution to replicate intricate multicellular structures.Therefore,this review outlines strategies to address these challenges,delving into(1)the development of suitable bioinks,(2)printing resolution optimization,and(3)rapid construction of complex biological structures and functions.Furthermore,the fundamental principles and evolution of projection slicing algorithms are explored,and the latest advancements in TVBP applications are summarized.Finally,we explore the future trajectory of this promising bio-manufacturing technology.展开更多
In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers ...In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers and neuromuscular junctions,we employed a vertical cryobioprinting-enabled ice-templating technique to create scaffolds with aligned microchannels.These channels facilitated cell-alignment,which is important in modeling neural and neuromuscular tissues.By integrating hyaluronic acid-methacrylate(HAMA)with gelatin methacryloyl and the necessary cryoprotective agent melezitose,we showcased that the cryobioink could preserve cell viability during freezinghawing processes,even at low temperatures employed during cryobioprinting.We optimized HAMA concentration to enhance neural cell viability and alignment,and successfully constructed anisotropic scaffolds featuring distinct sections that contained muscle and neural cells,establishing a model for neuromuscular junctions.The resulting models provide a versatile platform for studying nerve fibers and neuromuscular dysfunctions,offering potential advancements in neural regeneration research.展开更多
Skin,as the outermost layer of human body,serves as a barrier for avoiding external risks.However,skin may easily get injured due to traumatic damage and other diseases.Due to the shortage of donor sites,conventional ...Skin,as the outermost layer of human body,serves as a barrier for avoiding external risks.However,skin may easily get injured due to traumatic damage and other diseases.Due to the shortage of donor sites,conventional tissue engineering approaches have been broadly utilized for the formation of tissue-engineered skin.Meanwhile,artificial skin models could also be utilized as a testing platform for pre-clinical studies.However,conventional tissue engineering methods are struggling with the precise control of cell number and allocation,thereby restricting the level of vascularization and failing to fully recapitulate the complexity of native skin.More recently,three-dimensional(3D)bioprinting,on the basis of the advancements of additive manufacturing strategies,has recently appeared as a promising solution to simulate the anatomy and physiology of native skin,thereby providing an alternative fabrication method for vascularized skin models.However,despite technological advances and biomaterial innovations,current 3D bioprinting strategies and biomaterial choices are facing limitations in hierarchical vascular network recapitulation and microenvironment inadequacy for cellular activities.Therefore,this review systematically summarizes the biomaterial systems from natural,synthetic,and composite aspects combined with typical 3D bioprinting strategies from the basic building element,followed with the applications of 3D bioprinted vascularized skin constructs as in vitro skin models and in vivo skin grafts.Although there has been tremendous progress in the reconstruction of vascularized skin models,there remains a substantial gap in the functionality between the currently formed skin models and native skin due to biomaterial limitations,technical hurdles,and the structural and biological complexity of native skin.Herein,the future outlook for the reconstruction of vascularized skin models is discussed and summarized from materials innovations,technical improvements,and artificial intelligence(AI)incorporation.展开更多
Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to ...Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to create structures that closely mimic the complexity of native human tissues,facilitating advancements in regenerative medicine and personalized healthcare.This review paper systematically explores the challenges and design requirements in the fabrication of 3D biomimetic tissue constructs,emphasizing the need for advanced bioprinting strategies.Achieving biomimicry involves creating 3D anatomically relevant structures,biomimetic microenvironments,and vascularization.The focus is on overcoming existing bottlenecks through advancements in both fabrication techniques and bio-inks.Future directions in bioprinting are outlined,including multi-modal bioprinting systems,in-situ bioprinting,and the integration of machine learning into bioprinting processes.The critical role of bio-inks and printing methodologies in influencing cell viability is highlighted,providing insights into strategies for enhancing cellular functionality throughout the bioprinting process.Furthermore,the paper addresses post-fabrication considerations,particularly in accelerating tissue maturation,as a pivotal component for advancing the clinical applicability of bioprinted tissues.By navigating through the challenges,innovations,and prospects of advanced bioprinting strategies,this review highlights the transformative impact on tissue engineering.Pushing the boundaries of technological capabilities,these strategies hold the promise of groundbreaking advancements in regenerative medicine and personalized healthcare.Ultimately,the integration of these advanced techniques into bioprinting processes will pave the way for the development of more highly biomimetic and functional bioprinted tissues.展开更多
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
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
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
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
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
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
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
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
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
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
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 designesting.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
摘要Additive manufacturing,or 3D printing,has transformed tissue engineering by enabling the creation of intricate scaffolds and cell scaffold constructs that closely mimic organic tissues.This technique provides a foundation for creating structures that promote cell proliferation and tissue growth.The shift from 3D to 4D printing has introduced dynamic and time-responsive scaffolds that enhance the capabilities of tissue engineering by allowing constructs to modify their shape or function in response to environmental stimuli.These advancements are crucial for formulating adaptable treatments for human tissue regeneration.Bioprinting,a branch of 3D and 4D printing,incorporates living cells into printed constructs,resulting in cell-infused entities that harmoniously integrate with the human body.This method has considerable promise for producing live tissues;yet,both 3D/4D printing and bioprinting have technological limitations concerning precision,scalability,and functional intricacy.In response to these challenges,5D printing has emerged as a conceptual innovation beyond traditional dimensions.In 5D bioprinting,information serves as the fifth dimension and is embedded into printed objects along the dimensions of space and time.This supplementary information enables 5D-printed structures to interact more dynamically with their surroundings.Upon activation,this embedded information can alter ambient conditions or trigger functional responses inside printed objects,thereby enhancing the adaptability and integration with biological systems.This article presents a comprehensive analysis of 4D bioprinting methodologies in tissue engineering,followed by an exploration of the potential of 5D printing.5D bioprinting incorporates spatial,temporal,and informational dimensions,fostering innovative prospects in biomedical applications,and advancing the creation of intelligent scaffolds and adaptive biomaterials that can transform regenerative medicine and personalized healthcare.
基金financially supported by the National Natural Science Foundation of China(Nos.32471396,82230071,82172098,82201716,and 61973206)the National Key R&D Program of China(No.2023YFC2411303)+4 种基金the Integrated Project of Major Research Plan of the National Natural Science Foundation of China(No.92249303)the Shanghai Committee of Science and Technology(No.23141900600,Laboratory Animal Research Project)the Shanghai Clinical Research Plan of SHDC2023CRT01the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology(No.YESS20230049)the Baoshan District Health Commission Talents(Excellent Academic Leaders)Program(No.BSWSYX-2024-05)。
摘要With the rapid advancements in biomedical engineering,bioprinting has emerged as a pivotal solution to address the shortage of organ transplants and advance disease model research.The evolution of bioprinting has progressed from the fabrication of simple models(1.0)to the fabrication of permanent implants(2.0),tissue engineering scaffolds(3.0),and complex biostructures utilizing living cells(4.0).Nevertheless,significant challenges remain,particularly in accurately replicating the structure and function of host tissues,selecting appropriate materials,and optimizing printing parameters.The integration of artificial intelligence(AI),especially machine learning,provides promising novel opportunities in bioprinting(5.0).This review systematically summarizes the current applications of AI in bioprinting,discussing both construction strategies and application scenarios.It also explores the potential of AI to improve bioprinting in the preparation of complex functional tissues and in situ tissue repair.Overall,the synergy between AI and bioprinting is poised to drive the development of personalized medicine,facilitate high-throughput preparation of in vitro models,and provide robust tools for regenerative medicine and precision healthcare.
基金supported by the National Natural Science Foundation of China(52405325,52125501)the Key Research Project of Shaanxi Province(2024SF2-GJHX-34)+4 种基金the Postdoctoral Fellowship Program of CPSF(GZB20230573)the China Postdoctoral Science Foundation(2024M762577),the Postdoctoral Project of Shaanxi Province(2023BSHYDZZ30)the Open Research Fund of the State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration(2024KB04)the Open Research Fund of the State Key Laboratory for Manufacturing Systems Engineering(sklms2025014)the Fundamental Research Funds for the Central Universities and Open Research Fund of Xinjiang Uygur Autonomous Region Key Laboratory(2025D04009).
摘要Bioprinting provides an unparalleled tool for engineering living tissue constructs that mimic the structural organization of native skeletal muscles.However,it remains a challenge for existing bioprinting strategies to recapitulate the highly aligned cellular architectures inside skeletal muscles,primarily due to low printing resolution and limited capability for in situ microenvironmental regulation.Here,we propose to employ the electrical force during the electrohydrodynamic(EHD)bioprinting process to induce the in situ orientation of cell-laden fibrin-alginate hydrogel,which provides nanostructural guidance to the encapsulated cells for the formation of highly aligned skeletal muscle constructs.It was observed that the randomly distributed fibrin protofibril aggregates gradually elongated into uniformly aligned nanofibers at the Taylor cone stage as the applied voltage increased to 3 kV.The oriented fibrin nanofibers further direct in situ cellular alignment along the EHD bioprinting trajectory,facilitating the freeform fabrication of parallelly or circumferentially aligned muscle tissue constructs in vitro.The addition of conductive polymers into the fibrin-alginate hydrogel endows the EHD-bioprinted living constructs with muscle-specific conductivity and cellular organization,which promote myotube differentiation and maturation.The resultant aligned and conductive muscle constructs promoted in situ muscle regeneration and restored lost muscle functions at the defect regions in vivo.The presented EHD bioprinting strategy for fibrin-alginate hydrogel provides a versatile and simple platform to freely fabricate conductive,living tissue constructs with designer cellular alignments.
基金supported by Natural Science Foundation of Hubei Province(No.2019CFB457)Innovative Seed Funds of Medical College of Wuhan University(No.TFZZ2018027)Wuhan Medical Research Project(Youth Project)(No.WZ19Q02).
摘要Objective:To investigate the repair of spinal cord injury(SCI)in rats using 3D bioprinted decellularized extracellular matrix(dECM)hydrogel,neural stem cells(NSCs),and TGF-β1 monoclonal antibody.Methods:The spinal cord-derived dECM hydrogel(SC-dECM-gel)was optimized for 3D printing.Rheological tests established a 3%concentration as optimal.In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation.A rat SCI model was treated with the printed gel,and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials.Results:The 3%SC-dECM-gel showed superior rheological properties.TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro.In vivo,the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration.Conclusion:3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats,offering a promising approach for SCI treatment.
基金financially supported by the National Key Research and Development Program of China(No.2024YFB4610100)the National Natural Science Foundation of China(Nos.52235007,T2121004,and 52325504)the Science and Technology Planning Project of Guizhou Province(No.MS[2025]615).
摘要Tomographic volumetric bioprinting(TVBP)is an emerging transformative technology in bio-manufacturing,distinguished by two exceptional capabilities:ultrafast fabrication(centimeter-scale constructs within tens of seconds)and unique compatibility with ultra-soft bioinks(<102Pa).Despite its potential,TVBP remains in its infancy because of significant hurdles.These include the need to adapt conventional photocurable bioinks to TVBP’s unique photopolymerization requirements and achieve sufficient resolution to replicate intricate multicellular structures.Therefore,this review outlines strategies to address these challenges,delving into(1)the development of suitable bioinks,(2)printing resolution optimization,and(3)rapid construction of complex biological structures and functions.Furthermore,the fundamental principles and evolution of projection slicing algorithms are explored,and the latest advancements in TVBP applications are summarized.Finally,we explore the future trajectory of this promising bio-manufacturing technology.
基金support from the National Institutes of Technology(R21EB030257,R01EB028143,R01HL153857,R01HL166522,R01CA282451,R56EB034702)National Science Foundation(CBET-EBMS-1936105,CISE-IIS-2225698)+1 种基金Chan Zuckerberg Initiative(2022316712,2024-347836)the Brigham Research Institute.
摘要In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers and neuromuscular junctions,we employed a vertical cryobioprinting-enabled ice-templating technique to create scaffolds with aligned microchannels.These channels facilitated cell-alignment,which is important in modeling neural and neuromuscular tissues.By integrating hyaluronic acid-methacrylate(HAMA)with gelatin methacryloyl and the necessary cryoprotective agent melezitose,we showcased that the cryobioink could preserve cell viability during freezinghawing processes,even at low temperatures employed during cryobioprinting.We optimized HAMA concentration to enhance neural cell viability and alignment,and successfully constructed anisotropic scaffolds featuring distinct sections that contained muscle and neural cells,establishing a model for neuromuscular junctions.The resulting models provide a versatile platform for studying nerve fibers and neuromuscular dysfunctions,offering potential advancements in neural regeneration research.
基金the National Key Research and Development Program of China(Grant No.2024YFB4607700)the Opening Project of the Key Laboratory of Bionic Engineering(Ministry of Education),Jilin University(Grant No.KF202503)+2 种基金the Zhejiang Provincial Natural Science Foundation of China(Grant No.LDQ23E050001)the Postdoctoral Fellowship Program of CPSF(Grant No.GZB20240655)the Zhejiang Province Postdoctoral Research Project(Grant No.ZJ2024041).
摘要Skin,as the outermost layer of human body,serves as a barrier for avoiding external risks.However,skin may easily get injured due to traumatic damage and other diseases.Due to the shortage of donor sites,conventional tissue engineering approaches have been broadly utilized for the formation of tissue-engineered skin.Meanwhile,artificial skin models could also be utilized as a testing platform for pre-clinical studies.However,conventional tissue engineering methods are struggling with the precise control of cell number and allocation,thereby restricting the level of vascularization and failing to fully recapitulate the complexity of native skin.More recently,three-dimensional(3D)bioprinting,on the basis of the advancements of additive manufacturing strategies,has recently appeared as a promising solution to simulate the anatomy and physiology of native skin,thereby providing an alternative fabrication method for vascularized skin models.However,despite technological advances and biomaterial innovations,current 3D bioprinting strategies and biomaterial choices are facing limitations in hierarchical vascular network recapitulation and microenvironment inadequacy for cellular activities.Therefore,this review systematically summarizes the biomaterial systems from natural,synthetic,and composite aspects combined with typical 3D bioprinting strategies from the basic building element,followed with the applications of 3D bioprinted vascularized skin constructs as in vitro skin models and in vivo skin grafts.Although there has been tremendous progress in the reconstruction of vascularized skin models,there remains a substantial gap in the functionality between the currently formed skin models and native skin due to biomaterial limitations,technical hurdles,and the structural and biological complexity of native skin.Herein,the future outlook for the reconstruction of vascularized skin models is discussed and summarized from materials innovations,technical improvements,and artificial intelligence(AI)incorporation.
基金support from NTU Presidential Postdoctoral Fellowshipthe support from the National Research Foundation,Singapore,under its NRF Investigatorship(NRFNRFI07-2021-007,Funding Awardee:Wai Yee Yeong)。
摘要Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to create structures that closely mimic the complexity of native human tissues,facilitating advancements in regenerative medicine and personalized healthcare.This review paper systematically explores the challenges and design requirements in the fabrication of 3D biomimetic tissue constructs,emphasizing the need for advanced bioprinting strategies.Achieving biomimicry involves creating 3D anatomically relevant structures,biomimetic microenvironments,and vascularization.The focus is on overcoming existing bottlenecks through advancements in both fabrication techniques and bio-inks.Future directions in bioprinting are outlined,including multi-modal bioprinting systems,in-situ bioprinting,and the integration of machine learning into bioprinting processes.The critical role of bio-inks and printing methodologies in influencing cell viability is highlighted,providing insights into strategies for enhancing cellular functionality throughout the bioprinting process.Furthermore,the paper addresses post-fabrication considerations,particularly in accelerating tissue maturation,as a pivotal component for advancing the clinical applicability of bioprinted tissues.By navigating through the challenges,innovations,and prospects of advanced bioprinting strategies,this review highlights the transformative impact on tissue engineering.Pushing the boundaries of technological capabilities,these strategies hold the promise of groundbreaking advancements in regenerative medicine and personalized healthcare.Ultimately,the integration of these advanced techniques into bioprinting processes will pave the way for the development of more highly biomimetic and functional bioprinted tissues.
基金the Scientific and Technological Research Council of Turkey (TÜBİTAK) for their support through the TÜBİTAK 2211-A National PhD Fellowship Program
摘要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 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)。
摘要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 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).
摘要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 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).
摘要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sponsored by the National Natural Science Foundation of China(No.U1609207)。
摘要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)。
摘要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).
摘要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)。
摘要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 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).
摘要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.
摘要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 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.
摘要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.
摘要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 designesting.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.