As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands...As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ regeneration.Curated by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable organs.We further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control measures.Finally,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to ...Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to degraded tracking performance,particularly around high-acceleration segments and trajectory inflection points.This study investigates machine learning-based predictive compensation for latency mitigation in soft-tissue tracking.Three models—autoregressive(AR),long short-term memory(LSTM),and temporal convolutional network(TCN)—were implemented and evaluated on both synthetic and real datasets.By aligning the prediction horizon with the end-to-end system delay,we demonstrate that prediction-based compensation significantly reduces tracking errors.Among the models,TCN achieved superior robustness and accuracy on complex motion patterns,particularly in multi-step prediction tasks,and exhibited better latency–horizon compatibility.The results suggest that TCN is a promising candidate for real-time latency compensation in teleoperated robotic systems involving dynamic soft-tissue interaction.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention...BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.展开更多
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
Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the pot...Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the potential of photoacoustic imaging(PAI)in monitoring MWA by examining ex vivo porcine liver tissues.In this study,a comprehensive analysis of photoacoustic signals was performed to compare the main lobe width(MLW)between ablated and normal regions in porcine liver tissue.Histological staining with succinate dehydrogenase(SDH)and shear wave elastography(SWE)were employed to validate the changes in tissue elasticity after ablation.The analysis demonstrated a notable reduction in the MLW of the average A-lines in ablated tissues compared to nonablated regions(p<0.01).This reduction,attributed to increased tissue density and enhanced elasticity,indicates accelerated sound propagation in thermally ablated areas,which then serves as a critical parameter for mapping tissue characteristics.The reconstruction of the MLW distribution successfully delineated the ablated regions,and was consistent with the results of SDH staining and SWE.In addition,MLW-based imaging exhibited higher spatial resolution compared to SWE.Incorporating MLW analysis into PAI may be a promising strategy to improve the accuracy and effectiveness of MWA monitoring in clinical settings.展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Drug development and precision therapy are core technologies in the biopharmaceutical field.In the traditional paradigm,new drug development relies on validation through animal testing and clinical trials-a process th...Drug development and precision therapy are core technologies in the biopharmaceutical field.In the traditional paradigm,new drug development relies on validation through animal testing and clinical trials-a process that requires a decade of testing and costs over two billion dollars[1].Although animal testing has long served as the standard approach for evaluating drug efficacy and toxicity,its predictive accuracy for human responses remains limited due to translational barriers arising from interspecies physiological differences[2].Despite passing animal testing,only about 12%of drug candidates proceed to preclinical trials,and fewer than 11.7%gain final approval[3].展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)with...We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.展开更多
Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significa...Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.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
Medical models, or ＂phantoms,＂ have been widely used for medical training and for doctor-patient interactions. They are increasingly used for surgical planning, medical computational models, algorithm verification a...Medical models, or ＂phantoms,＂ have been widely used for medical training and for doctor-patient interactions. They are increasingly used for surgical planning, medical computational models, algorithm verification and validation, and medical devices development. Such new applications demand high-fidelity, patient-specific, tissue-mimicking medical phantoms that can not only closely emulate the geometric structures of human organs, but also possess the properties and functions of the organ structure. With the rapid advancement of three-dimensional （3D） printing and 3D bioprinting technologies, many researchers have explored the use of these additive manufacturing techniques to fabricate functional medical phantoms for various applications. This paper reviews the applications of these 3D printing and 3D bioprinting technologies for the fabrication of functional medical phantoms and bio-structures. This review specifically discusses the state of the art along with new developments and trends in 3D printed functional medical phantoms （i.e., tissue-mimicking medical phantoms, radiologically relevant medical phantoms, and physiological medical phantoms） and 3D bio-printed structures （i.e., hybrid scaffolding materials, convertible scaffolds, and integrated sensors） for regenerated tissues and organs.展开更多
The biomass, macroelements （N, P, K, Ca, Mg） and microelements （Fe, Zn） contents were detected in organs of 1a-3a Eucalyptus grandis saplings, as well as their accumulated amount. Results showed that contents of n...The biomass, macroelements （N, P, K, Ca, Mg） and microelements （Fe, Zn） contents were detected in organs of 1a-3a Eucalyptus grandis saplings, as well as their accumulated amount. Results showed that contents of nutrient elements varied greatly in different organs. Total contents of macroelements N, P, K, Ca and Mg in1a-3a E. grandis were distributed in the order of stem phloem, leaves 〉 branch- es, roots 〉 stem xylem. Accumulated amount of macroelements in 1a-3a E. grandis were in the order of leaves 〉 branches 〉 stem phloem 〉 roots or stem xylem 〉 stem xylem or roots. Accumulated amount law of nutrient elements was not affected by the plant age. Microelements Fe and Zn were mainly concentrated in the leaves and roots. The accumulation of macroelements was in the order of Ca 〉 N 〉 K 〉 Mg 〉 P; and the microelements was in the order of Fe 〉 Zn. Accumulated amounts of microelements in 1a-3a E. grandis were 12.45 136.19 and 420.23 g per plants, respectively. Among the annual net accumulated amount of nutrient ele- ments per plant in 1a-3a E. grandis, Ca element was the maximum, N and K ele- ments took the second and third places. Mg element was relatively small and P el- ement was the minimum.展开更多
Three-dimensional(3D)bioprinting is a rapidly growing technology that has been widely used in tissue engineering,disease studies,and drug screening.It provides the unprecedented capacity of depositing various types of...Three-dimensional(3D)bioprinting is a rapidly growing technology that has been widely used in tissue engineering,disease studies,and drug screening.It provides the unprecedented capacity of depositing various types of biomaterials,cells,and biomolecules in a layer-by-layer fashion,with precisely controlled spatial distribution.This technology is expected to address the organ-shortage issue in the future.In this review,we first introduce three categories of 3D bioprinting strategies:inkjet-based printing(IBP),extrusion-based printing(EBP),and light-based printing(LBP).Biomaterials and cells,which are normally referred to as“bioinks,”are then discussed.We also systematically describe the recent advancements of 3D bioprinting in fabricating cell-laden artificial tissues and organs with solid or hollow structures,including cartilage,bone,skin,muscle,vascular network,and so on.The development of organs-onchips utilizing 3D bioprinting technology for drug discovery and toxicity testing is reviewed as well.Finally,the main challenges in current studies and an outlook of the future research of 3D bioprinting are discussed.展开更多
Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications....Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.展开更多
Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Re...Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs.However,how chromatin organization differs among pig breeds is poorly understood.Results:In this study,we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots(upper layer of backfat[ULB]and greater omentum[GOM])in wild boars and Bama pigs;the latter is a typical indigenous pig in China.We found that over 95%of the A/B compartments and topologically associating domains(TADs)are stable between wild boars and Bama pigs.In contrast,more than 70%of promoterenhancer interactions(PEIs)are dynamic and widespread,involving over a thousand genes.Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions,endocrine function,energy metabolism and the immune response.Approximately 95%and 97%of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB,respectively.Conclusions:We reported 3D genome organization in adipose depots from different pig breeds.In a comparison of Bama pigs and wild boar,large-scale compartments and TADs were mostly conserved,while fine-scale PEIs were extensively reorganized.The chromatin architecture in these two pig breeds was reorganized in an adipose depotspecific manner.These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.展开更多
Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of ti...Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.展开更多
The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.T...The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52325504,52235007,and T2121004).
文摘As surgical procedures transition from conventional resection to advanced tissue-regeneration technologies,human disease therapy has witnessed a great leap forward.In particular,three-dimensional(3D)bioprinting stands as a landmark in this setting,by promising the precise integration of biomaterials,cells,and bioactive molecules,thus opening up a novel avenue for tissue/organ regeneration.Curated by the editorial board of Bio-Design and Manufacturing,this review brings together a cohort of leading young scientists in China to dissect the core functionalities and evolutionary trajectory of 3D bioprinting,by elucidating the intricate challenges encountered in the manufacturing of transplantable organs.We further delve into the translational pathway from scientific research to clinical application,emphasizing the imperativeness of establishing a regulatory framework and rigorously enforcing quality-control measures.Finally,this review outlines the strategic landscape and innovative achievements of China in this field and provides a comprehensive roadmap for researchers worldwide to propel this field collectively to even greater heights.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金Support by Sichuan Science and Technology Program[2023YFSY0026,2023YFH0004]Guangzhou Huashang University[2024HSZD01,HS2023JYSZH01].
文摘Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to degraded tracking performance,particularly around high-acceleration segments and trajectory inflection points.This study investigates machine learning-based predictive compensation for latency mitigation in soft-tissue tracking.Three models—autoregressive(AR),long short-term memory(LSTM),and temporal convolutional network(TCN)—were implemented and evaluated on both synthetic and real datasets.By aligning the prediction horizon with the end-to-end system delay,we demonstrate that prediction-based compensation significantly reduces tracking errors.Among the models,TCN achieved superior robustness and accuracy on complex motion patterns,particularly in multi-step prediction tasks,and exhibited better latency–horizon compatibility.The results suggest that TCN is a promising candidate for real-time latency compensation in teleoperated robotic systems involving dynamic soft-tissue interaction.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.
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 the National Natural Science Foundation of China(82427808,61875085)the Jiangsu Provincial University Natural Science Foundation(25KJB413004)+1 种基金the Nanjing Health Science and Technology Development Foundation(ZKX24043)the Fundamental Research Funds for the Central Universities(NJ2024029).
文摘Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the potential of photoacoustic imaging(PAI)in monitoring MWA by examining ex vivo porcine liver tissues.In this study,a comprehensive analysis of photoacoustic signals was performed to compare the main lobe width(MLW)between ablated and normal regions in porcine liver tissue.Histological staining with succinate dehydrogenase(SDH)and shear wave elastography(SWE)were employed to validate the changes in tissue elasticity after ablation.The analysis demonstrated a notable reduction in the MLW of the average A-lines in ablated tissues compared to nonablated regions(p<0.01).This reduction,attributed to increased tissue density and enhanced elasticity,indicates accelerated sound propagation in thermally ablated areas,which then serves as a critical parameter for mapping tissue characteristics.The reconstruction of the MLW distribution successfully delineated the ablated regions,and was consistent with the results of SDH staining and SWE.In addition,MLW-based imaging exhibited higher spatial resolution compared to SWE.Incorporating MLW analysis into PAI may be a promising strategy to improve the accuracy and effectiveness of MWA monitoring in clinical settings.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the Program of the National Natural Science Foundation of China(Grant Nos.:52435006,and 52275291)the Program for Innovation Team of Shaanxi Province The work was supported by the Program of the National Natural Science Foundation of China(Grant Nos.:52435006,and 52275291)the Program for Innovation Team of Shaanxi Province。
文摘Drug development and precision therapy are core technologies in the biopharmaceutical field.In the traditional paradigm,new drug development relies on validation through animal testing and clinical trials-a process that requires a decade of testing and costs over two billion dollars[1].Although animal testing has long served as the standard approach for evaluating drug efficacy and toxicity,its predictive accuracy for human responses remains limited due to translational barriers arising from interspecies physiological differences[2].Despite passing animal testing,only about 12%of drug candidates proceed to preclinical trials,and fewer than 11.7%gain final approval[3].
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金supported by the National Natural Science Foundation of China(Nos.32371470 and 82341019)the Department of Science and Technology of Guangdong Province(No.2023B0909020003).
文摘We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.
基金supported by the National Natural Science Foundation of China(82372535 to Ru-Lin Huang and 82361138568 to Qingfeng Li)the Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality(22MC1940300)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center(2023ZZ02023)。
文摘Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.
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)。
文摘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.
文摘Medical models, or ＂phantoms,＂ have been widely used for medical training and for doctor-patient interactions. They are increasingly used for surgical planning, medical computational models, algorithm verification and validation, and medical devices development. Such new applications demand high-fidelity, patient-specific, tissue-mimicking medical phantoms that can not only closely emulate the geometric structures of human organs, but also possess the properties and functions of the organ structure. With the rapid advancement of three-dimensional （3D） printing and 3D bioprinting technologies, many researchers have explored the use of these additive manufacturing techniques to fabricate functional medical phantoms for various applications. This paper reviews the applications of these 3D printing and 3D bioprinting technologies for the fabrication of functional medical phantoms and bio-structures. This review specifically discusses the state of the art along with new developments and trends in 3D printed functional medical phantoms （i.e., tissue-mimicking medical phantoms, radiologically relevant medical phantoms, and physiological medical phantoms） and 3D bio-printed structures （i.e., hybrid scaffolding materials, convertible scaffolds, and integrated sensors） for regenerated tissues and organs.
基金Supported by the Key Laboratory of Forest Ecology and Resource Environment of Sichuan Province~~
文摘The biomass, macroelements （N, P, K, Ca, Mg） and microelements （Fe, Zn） contents were detected in organs of 1a-3a Eucalyptus grandis saplings, as well as their accumulated amount. Results showed that contents of nutrient elements varied greatly in different organs. Total contents of macroelements N, P, K, Ca and Mg in1a-3a E. grandis were distributed in the order of stem phloem, leaves 〉 branch- es, roots 〉 stem xylem. Accumulated amount of macroelements in 1a-3a E. grandis were in the order of leaves 〉 branches 〉 stem phloem 〉 roots or stem xylem 〉 stem xylem or roots. Accumulated amount law of nutrient elements was not affected by the plant age. Microelements Fe and Zn were mainly concentrated in the leaves and roots. The accumulation of macroelements was in the order of Ca 〉 N 〉 K 〉 Mg 〉 P; and the microelements was in the order of Fe 〉 Zn. Accumulated amounts of microelements in 1a-3a E. grandis were 12.45 136.19 and 420.23 g per plants, respectively. Among the annual net accumulated amount of nutrient ele- ments per plant in 1a-3a E. grandis, Ca element was the maximum, N and K ele- ments took the second and third places. Mg element was relatively small and P el- ement was the minimum.
基金The authors would like to acknowledge support from the National Natural Science Foundation of China(51875518,51475419,and 81501607)the Natural Science Foundation of Zhejiang Province of China(LY15H160019)the Key Research and Development Projects of Zhejiang Province(2017C01054).
文摘Three-dimensional(3D)bioprinting is a rapidly growing technology that has been widely used in tissue engineering,disease studies,and drug screening.It provides the unprecedented capacity of depositing various types of biomaterials,cells,and biomolecules in a layer-by-layer fashion,with precisely controlled spatial distribution.This technology is expected to address the organ-shortage issue in the future.In this review,we first introduce three categories of 3D bioprinting strategies:inkjet-based printing(IBP),extrusion-based printing(EBP),and light-based printing(LBP).Biomaterials and cells,which are normally referred to as“bioinks,”are then discussed.We also systematically describe the recent advancements of 3D bioprinting in fabricating cell-laden artificial tissues and organs with solid or hollow structures,including cartilage,bone,skin,muscle,vascular network,and so on.The development of organs-onchips utilizing 3D bioprinting technology for drug discovery and toxicity testing is reviewed as well.Finally,the main challenges in current studies and an outlook of the future research of 3D bioprinting are discussed.
文摘Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.
基金supported by grants from the National Key R&D Program of China(2020YFA0509500)the National Natural Science Foundation of China(U19A2036,31772576,31530073 and 31802044)+1 种基金the Sichuan Science and Technology Program(2021YFYZ0009 and 2021YFYZ0030)the International Cooperation Project of Science and Technology Department of Sichuan Province(2021YFH0033).
文摘Background:A growing body of evidence has revealed that the mammalian genome is organized into hierarchical layers that are closely correlated with and may even be causally linked with variations in gene expression.Recent studies have characterized chromatin organization in various porcine tissues and cell types and compared them among species and during the early development of pigs.However,how chromatin organization differs among pig breeds is poorly understood.Results:In this study,we investigated the 3D genome organization and performed transcriptome characterization of two adipose depots(upper layer of backfat[ULB]and greater omentum[GOM])in wild boars and Bama pigs;the latter is a typical indigenous pig in China.We found that over 95%of the A/B compartments and topologically associating domains(TADs)are stable between wild boars and Bama pigs.In contrast,more than 70%of promoterenhancer interactions(PEIs)are dynamic and widespread,involving over a thousand genes.Alterations in chromatin structure are associated with changes in the expression of genes that are involved in widespread biological functions such as basic cellular functions,endocrine function,energy metabolism and the immune response.Approximately 95%and 97%of the genes associated with reorganized A/B compartments and PEIs in the two pig breeds differed between GOM and ULB,respectively.Conclusions:We reported 3D genome organization in adipose depots from different pig breeds.In a comparison of Bama pigs and wild boar,large-scale compartments and TADs were mostly conserved,while fine-scale PEIs were extensively reorganized.The chromatin architecture in these two pig breeds was reorganized in an adipose depotspecific manner.These results contribute to determining the regulatory mechanism of phenotypic differences between Bama pigs and wild boar.
文摘Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.
基金supported by the National Natural Science Foundation of China(Grant No.52473121,52403370 and 52221006)Fundamental Research Funds for the Central Universities(buctrc202020,buctrc202312).
文摘The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
