The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a...The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a promising alternative solution,their fabrication is difficult due to the complex structure and function of the esophagus.This review describes the existing fabrication methods for esophageal tubular scaffolds,including decellularization,casting,electrospinning,three dimensional(3 D)bioprinting,and pin-frogging.Also discussed are the stimulation cues of the fabricated esophageal tubular scaffold that induce esophageal muscle and epithelial cells.Finally,this review emphasizes three important concerns for esophageal tubular scaffolds:leakage and porosity,elasticity and proliferation of smooth muscle cells,and biocompatibility and structural fidelity of biomaterials.展开更多
Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury...Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.展开更多
The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infan...The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.展开更多
Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects....Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.展开更多
Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerg...Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.展开更多
The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of...The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.展开更多
Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired b...Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.展开更多
This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional trea...This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional treatments like autografts and allografts.The study highlights the integration of 3D bioprinting,stem cell therapy,gene therapy,biomaterials,nanotechnology,and computational modeling as transformative approaches in BTE.Developing biomimetic scaffolds,advanced bio-inks,and composite nanomaterials has enhanced seaffold design,improving mechanical properties and biocompatibility.Innovatiohs in gene therapy and bioactive molecule delivery are showcased for their ability to modulate cellular behavior and enhance osteogenesis.Stem cell-based therapies leverage the regenerative potential of mesenchymal stem cells,facilitating tissue integration and functional restoration.Computational tools,including finite element analysis(FEA)and agent-based modelling,aid in the optimization of scaffold design,predicting mechanical responses and biological behaviors.Despite notable progress,signifieant challenges,such as achieving reliable vascularization,sealable manu-facturing of engineered constructs,and effective clinical translation,remain substantial barriers to widespread adoption.Future research efforts focused on refining these technologies are vital for translating innovative strategies into elinical practice,paving the way for personalized regenerative solutions in bone repair.展开更多
Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements h...Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.展开更多
Oral and maxillofacial reconstruction represents one of the most complex challenges in plastic and reconstructive surgery,requiring the restoration of both form and function in highly specialized anatomical regions.Tr...Oral and maxillofacial reconstruction represents one of the most complex challenges in plastic and reconstructive surgery,requiring the restoration of both form and function in highly specialized anatomical regions.Traditional strategies,including local flaps and autologous bone grafts,remain fundamental but are limited by donor-site morbidity,tissue availability,and unpredictable outcomes.Recent advances in regenerative medicine have shifted the paradigm from repair to true regeneration,harnessing stem cells,biomaterial scaffolds,and signaling molecules in a synergistic approach.Dental-and craniofacial tissue-derived mesenchymal stem cells,along with adipose-derived stem cells,demonstrate significant potential for alveolar bone repair,periodontal regeneration,and soft tissue augmentation.Innovations in three-dimensional printing and bioactive matrices have enabled precise scaffold design and improved vascularization,thereby enhancing both predictability and esthetic outcomes.This mini review focuses on the synergistic role of stem cells,scaffolds,and signaling molecules in oral and maxillofacial regeneration,with an emphasis on the unique contributions of periodontists.By integrating periodontal biology with reconstructive techniques,a new collaborative framework is emerging to optimize regenerative outcomes.Future research must address clinical translation,large-scale trials,cost-effectiveness,and personalized approaches to fully realize the promise of regenerative surgery.展开更多
Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides...Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides the directional migration and spatial arrangement of cells through the mechanical signal transduction mediated by integrin.Surface functionalization can synergistically activate the osteogenic transcription network and significantly enhance the osteogenic differentiation potential of cells.The precise design of scaffold stiffness affects the cell fate choice by regulating the nuclear translocation of mechanical sensitive factors.This triple cooperative strategy of“physical topology-biochemical signal-mechanical microenvironment”effectively overcomes the biological inertia of traditional scaffolds and provides a dynamic and adjustable platform for bone defect repair.Looking forward to the future,breaking through the bottleneck of clinical transformation such as long-term intelligent slow release of functional factors and in situ efficient construction of vascular network is the key to promoting nanofiber scaffolds from basic research to precise bone regeneration treatment.展开更多
Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also ...Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.展开更多
Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned na...Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned nanofiber scaffolds with cyclic uniaxial stretching to promote tenogenic differentiation in bone marrow-derived mesenchymal stem cells.Their results provide critical insight into how structural and mechanical cues can synergize to generate ligament-like tissue in vitro.This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.展开更多
In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through top...In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.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 freezing/thawing 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
With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These mod...With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These models effectively mimic the complex structure and functions of human skin.This review comprehensively discusses the latest advancements in construction techniques,material selection,and applications of 3D skin models.It highlights the advantages and challenges associated with cutting-edge technologies such as layer-by-layer cell coating,3D bioprinting,bio-spray technology,and photolithographic microfabrication in creating highly realistic skin models.Moreover,it examines the wide-ranging applications of 3D skin models,includingelucidation of skin disease mechanisms,investigation of skin barrier functions,studies on skin aging and repair,hair regeneration,efficacy screening of therapeutic agents,cosmetic safety assessment,and personalized medicine.Finally,this review anticipates future trends in developing 3D skin models with greater structural and functional complexity,enhanced multifunctionality,and improved clinical translation.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional ...AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.展开更多
The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechani...The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.展开更多
基金support from the National Natural Science Foundation of China(No.82472440)Hubei Provincial Natural Science Foundation of China(No.2023AFB141)+1 种基金the National Medical Products Administration Key Laboratory for Dental Materials(No.PKUSS20240401)the Cross-Research Support Program from Huazhong University of Science and Technology。
文摘The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a promising alternative solution,their fabrication is difficult due to the complex structure and function of the esophagus.This review describes the existing fabrication methods for esophageal tubular scaffolds,including decellularization,casting,electrospinning,three dimensional(3 D)bioprinting,and pin-frogging.Also discussed are the stimulation cues of the fabricated esophageal tubular scaffold that induce esophageal muscle and epithelial cells.Finally,this review emphasizes three important concerns for esophageal tubular scaffolds:leakage and porosity,elasticity and proliferation of smooth muscle cells,and biocompatibility and structural fidelity of biomaterials.
基金supported by funding from the U.S.Department of Defense,Nos.W911NF-23-1-0276,W81XWH2211065the NIH,No.P41EB027062(all to DLK).
文摘Traumatic brain injury causes permanent cell death and can lead to long-term cognitive dysfunction,with no available treatments to repair the damaged brain tissue.Methods to track and understand traumatic brain injury in humans are severely limited by the inaccessibility of living brain tissue,creating a need for in vitro model systems to study cellular mechanisms of degeneration and regeneration following injury.Here we describe methods to establish a 3D human brain tissue model,consisting of a silk-collagen composite scaffold seeded with human neurons,astrocytes,and microglia,to study neuro-regeneration after traumatic brain injury.Step-by-step fabrication,injury,and analytical assessments of the 3D“triculture”system are described.Using this tissue model system,we demonstrate that glial cells promote regeneration of neuronal networks within the injury site over several weeks post-injury.Further,we found that regenerating networks in the 3D triculture tissues did not secrete early markers of neurodegenerative disease,but displayed signs of excitatory/inhibitory imbalance,suggesting that pro-regenerative treatments for traumatic brain injury in the future may need to direct cell differentiation to promote proper function.The mechanical stability of this model system enables physiologically relevant impact injury and long-term culture capability,while its modular design enables modification of cell contents,extracellular matrix composition,and scaffold properties.This adaptability could allow the integration of patient-derived cells and genetic modifications to bridge research and clinical applications focused on personalized targeted therapies.This in vitro system provides a valuable platform for accelerating therapeutic advancements in traumatic brain injury and neurodegenerative disorders,ultimately improving patient outcomes.
文摘The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.
文摘Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.
基金supported by the‘Korea National Institute of Health’research project(2022ER130502)a grant from by SMC-SKKU Future Convergence Academic Research Program,2024supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00336758)。
文摘Biomedical scaffold fabrication has seen advancements in mimicking the native extracellular matrix through intricate three-dimensional(3D)structures conducive to tissue regeneration.Coiled fibrous scaffolds have emerged as promising substrates owing to their ability to provide unique topographical cues.In this study,coiled poly(ε-caprolactone)(PCL)fibrous bundles were fabricated using an alginate-based composite system,and processed with 3D printing.The unique structure was obtained through the die-swell phenomenon related to the release of residual stresses from the printed strut,thereby transforming aligned PCL fibers into coiled structures.The effects of printing parameters,such as pneumatic pressure and nozzle moving speed,on fiber morphology were investigated to ensure a consistent formation of coiled PCL fibers.The resulting coiled PCL fibrous scaffold demonstrated higher activation of mechanotransduction signaling as well as upregulation of osteogenic-related genes in human adipose stem cells(hASCs),supporting its potential in bone tissue engineering.
文摘The field of bone tissue engineering has experienced an increase in prevalence due to the inherent challenge of the natural regeneration of significant bone deformities.This investigation focused on the preparation of Three-Dimensional(3D)-printed Polycaprolactone(PCL)scaffolds with varying proportions of Nanohydroxyapatite(NHA)and Nanoclay(NC),and their physiochemical and biological properties were assessed.The mechanical properties of PCL are satisfactory;however,its hydrophobic nature and long-term degradation hinder its use in scaffold fabrication.NHA and NC have been employed to improve the hydrophilic characteristics,mechanical strength,adhesive properties,biocompatibility,biodegradability,and osteoconductive behavior of PCL.The morphology results demonstrated 3D-printed structures with interconnected rectangular macropores and proper nanoparticle distribution.The sample containing 70 wt%NC showed the highest porosity(65.98±2.54%),leading to an increased degradation rate.The compressive strength ranged from 10.65±1.90 to 84.93±9.93 MPa,which is directly proportional to the compressive strength of cancellous bone(2–12 MPa).The wettability,water uptake,and biodegradability of PCL scaffolds considerably improved as the amount of NC increased.The results of the cellular assays exhibited increased proliferation,viability,and adhesion of MG-63 cells due to the addition of NHA and NC to the scaffolds.Finally,according to the in vitro results,it can be concluded that 3D-printed samples with higher amounts of NC can be regarded as a suitable scaffold for expediting the regeneration process of bone defects.
基金financially supported by the National Natural Science Foundation of China(Nos.52103184 and 8226030956)the National Key Research and Development Program of China(No.2022YFC2407503)+3 种基金Key Project of the Natural Science Basic Research Plan of Shaanxi Province(No.2022JZ43)Natural Science Basic Research Program of Shaanxi Province(No.2024JCYBQN-0874)Medical Research Key Project of Xi'an Science and Technology Bureau(No.2024JH-YXZD-0055)Medical Research Project of Xi'an Science and Technology Bureau(No.22YXYJ0083)
文摘Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
基金the Deanship of Scientific Research at King Khalid University for funding this study through the Large Research Group Project under grant number"RGP 2/365/45".
文摘This review article presents a comprehensive overview of emerging technologies in bone tissue engineering(BTE).This rapidly advancing field addresses the challenges of bone defects and injuries beyond traditional treatments like autografts and allografts.The study highlights the integration of 3D bioprinting,stem cell therapy,gene therapy,biomaterials,nanotechnology,and computational modeling as transformative approaches in BTE.Developing biomimetic scaffolds,advanced bio-inks,and composite nanomaterials has enhanced seaffold design,improving mechanical properties and biocompatibility.Innovatiohs in gene therapy and bioactive molecule delivery are showcased for their ability to modulate cellular behavior and enhance osteogenesis.Stem cell-based therapies leverage the regenerative potential of mesenchymal stem cells,facilitating tissue integration and functional restoration.Computational tools,including finite element analysis(FEA)and agent-based modelling,aid in the optimization of scaffold design,predicting mechanical responses and biological behaviors.Despite notable progress,signifieant challenges,such as achieving reliable vascularization,sealable manu-facturing of engineered constructs,and effective clinical translation,remain substantial barriers to widespread adoption.Future research efforts focused on refining these technologies are vital for translating innovative strategies into elinical practice,paving the way for personalized regenerative solutions in bone repair.
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
文摘Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
基金supported by grants from the National Natural Science Foundation of China(92368207)the Chinese Academy of Engineering(2023-SBZD-11)the Natural Science Foundation of Jiangsu Province(BK20232023).
文摘Tissue engineering and regenerative medicine is a new interdisciplinary subject integrating life science,material science,engineering technology,and clinical medicine.Over the last ten years,significant advancements have been achieved in the study of biomaterials and tissue engineering.Progress in the field of tissue engineering and regenerative medicine can result in optimal tissue regeneration and effective functional reconstruction.Spinal cord injury(SCI)is the most severe complication of spinal trauma and frequently results in significant functional impairments in the lower extremities of the affected segment.Repair of SCI is a medical challenge worldwide.Advancements in tissue engineering theory and technology offer fresh opportunities for addressing SCI,as well as providing new strategies and methodologies to tackle the challenges associated with repairing and reconstructing spinal cord function.This article provides an overview of the latest developments in tissue engineering and SCI repair,focusing on biomaterials,cells,and active factors.It also introduces nine key components related to SCI and proposes innovative approaches for repairing and functionally reconstructing the injured spinal cord.
文摘Oral and maxillofacial reconstruction represents one of the most complex challenges in plastic and reconstructive surgery,requiring the restoration of both form and function in highly specialized anatomical regions.Traditional strategies,including local flaps and autologous bone grafts,remain fundamental but are limited by donor-site morbidity,tissue availability,and unpredictable outcomes.Recent advances in regenerative medicine have shifted the paradigm from repair to true regeneration,harnessing stem cells,biomaterial scaffolds,and signaling molecules in a synergistic approach.Dental-and craniofacial tissue-derived mesenchymal stem cells,along with adipose-derived stem cells,demonstrate significant potential for alveolar bone repair,periodontal regeneration,and soft tissue augmentation.Innovations in three-dimensional printing and bioactive matrices have enabled precise scaffold design and improved vascularization,thereby enhancing both predictability and esthetic outcomes.This mini review focuses on the synergistic role of stem cells,scaffolds,and signaling molecules in oral and maxillofacial regeneration,with an emphasis on the unique contributions of periodontists.By integrating periodontal biology with reconstructive techniques,a new collaborative framework is emerging to optimize regenerative outcomes.Future research must address clinical translation,large-scale trials,cost-effectiveness,and personalized approaches to fully realize the promise of regenerative surgery.
文摘Nanofiber scaffold has built a bionic microenvironment for bone marrow mesenchymal stem cells by highly simulating the topological structure of natural extracellular matrix.Its ordered fiber network effectively guides the directional migration and spatial arrangement of cells through the mechanical signal transduction mediated by integrin.Surface functionalization can synergistically activate the osteogenic transcription network and significantly enhance the osteogenic differentiation potential of cells.The precise design of scaffold stiffness affects the cell fate choice by regulating the nuclear translocation of mechanical sensitive factors.This triple cooperative strategy of“physical topology-biochemical signal-mechanical microenvironment”effectively overcomes the biological inertia of traditional scaffolds and provides a dynamic and adjustable platform for bone defect repair.Looking forward to the future,breaking through the bottleneck of clinical transformation such as long-term intelligent slow release of functional factors and in situ efficient construction of vascular network is the key to promoting nanofiber scaffolds from basic research to precise bone regeneration treatment.
基金financially supported by the following programs:National Key Research and Development Program of China(No.2023YFB3813003)National Natural Science Foundation of China(Nos.82430031,82122014,82071085)+1 种基金Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001)the Central Universities(No.2022FZZX01-33)。
文摘Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury(PNI),not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell(SC)cords migration and axons elongation.Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects,systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce.This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration,and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them,encompassing(1)in vitro prevascularization,(2)in vivo prevascularization,and(3)stimulation of neurovascularization in situ.Furthermore,we emphasize that the lack of accuracy for structure and spatiotemporal regulation,as well as the operational inconvenience and delayed connection to the host's nerve stumps,have stuck the existing neurovascularization technology in the preclinical stage.The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.NRF-2022R1I1A1A01068652.
文摘Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned nanofiber scaffolds with cyclic uniaxial stretching to promote tenogenic differentiation in bone marrow-derived mesenchymal stem cells.Their results provide critical insight into how structural and mechanical cues can synergize to generate ligament-like tissue in vitro.This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.
基金National Natural Science Foundation Council of China(Grant No.52305359)Hubei Provincial Natural Science Foundation of China(Grant No.2023AFB141)National Medical Products Administration Key Laboratory for Dental Materials(PKUSS20240401)。
文摘In tissue engineering(TE),tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo,thereby inducing endogenous tissue regeneration through topological cues.An ideal TE scaffold should possess biomimetic cross-scale structures,similar to that of natural extracellular matrices,at the nano-to macro-scale level.Although freeform fabrication of TE scaffolds can be achieved through 3D printing,this method is limited in simultaneously building multiscale structures.To address this challenge,low-temperature fields were adopted in the traditional fabrication processes,such as casting and 3D printing.Ice crystals grow during scaffold fabrication and act as a template to control the nano-and micro-structures.These microstructures can be optimized by adjusting various parameters,such as the direction and magnitude of the low-temperature field.By preserving the macro-features fabricated using traditional methods,additional micro-structures with smaller scales can be incorporated simultaneously,realizing cross-scale structures that provide a better mimic of natural organs and tissues.In this paper,we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting,cryogenic3D printing,and freeze spinning.Fundamental working principles,fabrication setups,processes,and examples of biomedical applications are introduced.The challenges and outlook for low-temperature-assisted fabrication are also discussed.
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.
文摘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 freezing/thawing 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.
文摘With the increasing demand for understanding skin physiology and advancing regenerative medicine,in vitro three-dimensional(3D)functional skin tissue models have become vital tools in dermatological research.These models effectively mimic the complex structure and functions of human skin.This review comprehensively discusses the latest advancements in construction techniques,material selection,and applications of 3D skin models.It highlights the advantages and challenges associated with cutting-edge technologies such as layer-by-layer cell coating,3D bioprinting,bio-spray technology,and photolithographic microfabrication in creating highly realistic skin models.Moreover,it examines the wide-ranging applications of 3D skin models,includingelucidation of skin disease mechanisms,investigation of skin barrier functions,studies on skin aging and repair,hair regeneration,efficacy screening of therapeutic agents,cosmetic safety assessment,and personalized medicine.Finally,this review anticipates future trends in developing 3D skin models with greater structural and functional complexity,enhanced multifunctionality,and improved clinical translation.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
文摘AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.
基金financially supported by the National Natural Science Foundation of China(Nos.52125501,52405325)the Key Research Project of Shaanxi Province(Nos.2021LLRH-08,2024SF2-GJHX-34)+5 种基金the Program for Innovation Team of Shaanxi Province(No.2023-CX-TD17)the Postdoctoral Fellowship Program of CPSF(No.GZB20230573)the Postdoctoral Project of Shaanxi Province(No.2023BSHYDZZ30)the Basic Research Program of Natural Science in Shaanxi Province(No.2021JQ-906)the China Postdoctoral Science Foundationthe Fundamental Research Funds for the Central Universities。
文摘The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.
