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
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
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
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
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
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
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
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
Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the...Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.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
Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transit...Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transition of tissue from a solid-like state to a fluid-like state,plays a pivotal role in enabling the reorganization of the epidermal structure and cellular spatial order,which is essential for effective tissue expansion.Drawing parallels between fluidity in materials science and biological systems,we suggest that the fluid-like behavior in the skin may be critical for mechanical adaptability.Understanding the influence of tissue fluidity may open pathways for modulating this process,potentially enhancing tissue expansion efficiency,reducing procedural duration,and improving clinical outcomes.This perspective highlights the importance of investigating the biological dynamics of tissue fluidity and exploring the potential for targeted manipulation of fluidity-related pathways to optimize tissue expansion.Such advancements could profoundly affect regenerative and reconstructive surgical practices.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales hav...The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.展开更多
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
Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,lim...Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.展开更多
BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,b...BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,biological,or artificial dressings.Biological and artificial dressings,such as hydrogels,are preferred for their biocompatibility.Platelet concentrates,such as platelet-rich plasma(PRP)and platelet-rich fibrin(PRF),stand out for accelerating tissue repair and minimizing risks of allergies and rejection.This study developed PRF and PRP-based dressings to treat skin wounds in an animal model,evaluating their functionality and efficiency in accelerating the tissue repair process.AIM To develop wound dressings based on platelet concentrates and evaluating their efficiency in treating skin wounds in Wistar rats.METHODS Wistar rats,both male and female,were subjected to the creation of a skin wound,distributed into groups(n=64/group),and treated with Carbopol(negative control);PRP+Carbopol;PRF+Carbopol;or PRF+CaCl_(2)+Carbopol,on days zero(D0),D3,D7,D14,and D21.PRP and PRF were obtained only from male rats.On D3,D7,D14,and D21,the wounds were analyzed for area,contraction rate,and histopathology of the tissue repair process.RESULTS The PRF-based dressing was more effective in accelerating wound closure early in the tissue repair process(up to D7),while PRF+CaCl_(2) seemed to delay the process,as wound closure was not complete by D21.Regarding macroscopic parameters,animals treated with PRF+CaCl_(2) showed significantly more crusting(necrosis)early in the repair process(D3).In terms of histopathological parameters,the PRF group exhibited significant collagenization at the later stages of the repair process(D14 and D21).By D21,fibroblast proliferation and inflammatory infiltration were higher in the PRP group.Animals treated with PRF+CaCl_(2) experienced a more pronounced inflammatory response up to D7,which diminished from D14 onwards.CONCLUSION The PRF-based dressing was effective in accelerating the closure of cutaneous wounds in Wistar rats early in the process and in aiding tissue repair at the later stages.展开更多
Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT paramet...Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.展开更多
Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation...Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
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 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.
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.
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.
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Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.
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 National Natural Science Foundation of China(grant nos.82102343 and 82372536)the Shanghai Municipal Health Commission Health Industry Clinical Research Special Program(grant no.20244Y0031)the Shanghai“Rising Stars of Medical Talents”Youth Development Program(Youth Medical Talents-Specialist Program).
文摘Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transition of tissue from a solid-like state to a fluid-like state,plays a pivotal role in enabling the reorganization of the epidermal structure and cellular spatial order,which is essential for effective tissue expansion.Drawing parallels between fluidity in materials science and biological systems,we suggest that the fluid-like behavior in the skin may be critical for mechanical adaptability.Understanding the influence of tissue fluidity may open pathways for modulating this process,potentially enhancing tissue expansion efficiency,reducing procedural duration,and improving clinical outcomes.This perspective highlights the importance of investigating the biological dynamics of tissue fluidity and exploring the potential for targeted manipulation of fluidity-related pathways to optimize tissue expansion.Such advancements could profoundly affect regenerative and reconstructive surgical practices.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金supported by the National Natural Science Foundation of China(Grant No.U2241273)the Beijing Municipal Natural Science Foundation(Grant No.Z240017)+3 种基金the 111 project(Grant No.B13003)the Fundamental Research Funds for the Central Universitiesthe China Scholarship Councilthe Academic Excellence Foundation of BUAA for PhD Students.
文摘The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.
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(No.52105072)Zhejiang Provincial Natural Science Foundation of China(No.LZ24E050004)+2 种基金Jiangsu Provincial Outstanding Youth Program(No.BK20230072)a grant from Suzhou Industrial Foresight and Key Core Technology Project(No.SYC2022044)grants from Jiangsu Qinglan Project and Jiangsu 333 High-level Talents.
文摘Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.
文摘BACKGROUND Skin wounds are common injuries that affect quality of life and incur high costs.A considerable portion of healthcare resources in Western countries is allocated to wound treatment,mainly using mechanical,biological,or artificial dressings.Biological and artificial dressings,such as hydrogels,are preferred for their biocompatibility.Platelet concentrates,such as platelet-rich plasma(PRP)and platelet-rich fibrin(PRF),stand out for accelerating tissue repair and minimizing risks of allergies and rejection.This study developed PRF and PRP-based dressings to treat skin wounds in an animal model,evaluating their functionality and efficiency in accelerating the tissue repair process.AIM To develop wound dressings based on platelet concentrates and evaluating their efficiency in treating skin wounds in Wistar rats.METHODS Wistar rats,both male and female,were subjected to the creation of a skin wound,distributed into groups(n=64/group),and treated with Carbopol(negative control);PRP+Carbopol;PRF+Carbopol;or PRF+CaCl_(2)+Carbopol,on days zero(D0),D3,D7,D14,and D21.PRP and PRF were obtained only from male rats.On D3,D7,D14,and D21,the wounds were analyzed for area,contraction rate,and histopathology of the tissue repair process.RESULTS The PRF-based dressing was more effective in accelerating wound closure early in the tissue repair process(up to D7),while PRF+CaCl_(2) seemed to delay the process,as wound closure was not complete by D21.Regarding macroscopic parameters,animals treated with PRF+CaCl_(2) showed significantly more crusting(necrosis)early in the repair process(D3).In terms of histopathological parameters,the PRF group exhibited significant collagenization at the later stages of the repair process(D14 and D21).By D21,fibroblast proliferation and inflammatory infiltration were higher in the PRP group.Animals treated with PRF+CaCl_(2) experienced a more pronounced inflammatory response up to D7,which diminished from D14 onwards.CONCLUSION The PRF-based dressing was effective in accelerating the closure of cutaneous wounds in Wistar rats early in the process and in aiding tissue repair at the later stages.
基金Supported by the Health Commission of the Sichuan Province Medical Science and Technology Program,China,No.24WXXT10the Sichuan Province Science and Technology Support Program,China,No.2021YJ0242the 23rd Batch of Student Scientific Research Project Approval of Jiangsu University,China,No.Y23A164.
文摘Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)the Shanxi Provincial Key Medical Scientific Research Project(No.2020XM06)+2 种基金the Shanxi Provincial Basic Research Project(Nos.202103021221006,20210302123040,and 202103021223069)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
