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
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
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
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
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
Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within thes...Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.展开更多
Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and ...Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and uses new diagnostic parameters related to the"phsse WAvEs of local depolarization".We combined polarization-interferenæregistration with phase scanning of complex amplitude distributions in diffuse Laser speckle fields to detect phase waves of local depolarization in birefringent fibrillar networks of biological tisue and messure their modulation depth.This eppгоsch led to the discovery of new criteria for differentiating verious necrotic changes in diffuse histological samples of myocardial tisue from decmsed individuals with"ischemic heart disase(IHD)--cute coronary insufficiency(ACT)",even in the presænce of a high level of depolarized bckground.To evaluate the degree of necrotic changes in the optical anisotropy of difuse myocardial Layers,a new quantitative parameter--modulation depth of local depolarization wave fluctustions-has been proposed.Using this approsch,for the first time,differentiation of diffuse myocardial samples from decessed individuals with IHD and ACI was achieved witha very good 90.45%and outstanding aocuracy of 95.2%.展开更多
Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distri...Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distribution and function have gained considerable attention because of their profound impact on metabolic health and overall well-being.Subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)are the two major depots of white adipose tissue,each with distinct roles in metabolism and health.Understanding the characteristics and underlying mechanisms of SAT and VAT is crucial for elucidating the aging process and developing strategies to promote healthy aging.This review focuses on delineating and analyzing the characteristics and intrinsic mechanisms underlying the aging of subcutaneous and visceral adipose tissue during the aging process,which can contribute to a better understanding of the aging process and enhance healthy aging.展开更多
A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interact...A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interactions,fostering cell growth,differentiation,and organization.However,challenges persist in decellularization,necessitating a balance between preserving the ECM structural integrity and achieving effective cellular removal.An approach to enhancing decellularization involves pre-eliminating unnecessary tissues and effectively reducing final DNA levels to lower than 50 ng/mg ECM on preprocessed tissues.Although this strategic step augments decellularization efficiency,the current manual execution method depends on the operator’s skill.To address this limitation,this study proposed an automated raw tissue slicing system that does not require tissue preparation for slicing.Through carefully controlled tissue applanation pressure and oscillatory incisions with optimized parameters,the system achieved a precision within±10µm in obtaining submillimeter-scale tissue slices of the porcine cornea while avoiding significant microscopic complications in the tissue structure,as observed by tissue histology.These findings suggested the system’s capability to streamline and automate preliminary tissue slicing operations.The efficacy of this approach for decellularization was validated by processing porcine corneas using the proposed system and subsequently decellularizing the processed tissues.DNA level analysis revealed that sliced,subdivided tissues created by this system could expedite DNA reduction even at the initial steps of decellularization,enhancing the overall decellularization procedure.展开更多
Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
During restorative dental procedures,complete control over the operative site is critical for patient comfort,safety,and the operator’s access and visibility.The success of a fixed prosthesis depends on accurate impr...During restorative dental procedures,complete control over the operative site is critical for patient comfort,safety,and the operator’s access and visibility.The success of a fixed prosthesis depends on accurate impression making of the prepared finish lines on the abutment teeth.To optimise long-term outcomes for the fixed restoration,gingival retraction techniques should be used to decrease the marginal discrepancy among the restoration and the prepared abutment.Accurate marginal positioning of the restoration along the prepared finish line of the abutment is essential for therapeutic,preventive,and aesthetic purposes.展开更多
Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal sympto...Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.展开更多
Craniofacial muscles are essential components of the skeletal muscular system that contribute to important physiological processes.Severe trauma can induce craniofacial volumetric muscle loss(VML),which impairs muscle...Craniofacial muscles are essential components of the skeletal muscular system that contribute to important physiological processes.Severe trauma can induce craniofacial volumetric muscle loss(VML),which impairs muscle regeneration,causes facial muscular deformities and functional disability,and leads to psychosocial consequences such as isolation and depression.Conventional therapies involving muscle flap transposition or autologous tissue grafting achieve morphological repair but are ineffective in restoring muscle function,resulting in donor site injury and sensory deficit.In this study,we successfully constructed a biomimetically engineered muscle tissue that integrates myofiber alignment,effective innervation,and blood perfusion to promote multi-tissue regeneration in the masseter area in vivo,enabling functional regeneration.Using light-controlled micropatterning technology,we constructed mature muscle fibers with oriented alignment and established a neuromuscular co-culture system for in vitro neuromuscular junction reconstruction.Furthermore,we designed and fabricated a vascular network structure to promote tissue vascularization using hydrogel as the vehicle for assembling the composite engineered tissue.Using this technology,the shape and dimension of the constructed entity can be customized to address various muscle defects,enabling individualized repair.This study offers a promising novel strategy for tissue regeneration that breaks through the current challenges in the treatment of craniofacial VML.展开更多
AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trau...AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.展开更多
Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuo...Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuous light exposure.This study aimed to investigate the morphological and functional alterations in BAT under continuous light conditions and to identify traditional Chinese medicine compounds capable of reversing these changes.Methods:A metabolic disorder model was established by subjecting mice to continuous light exposure for 5 weeks.During this period,body weight,food intake,and body fat percentage were monitored.Serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured to assess lipid metabolism.Histological changes in BAT were examined using H&E staining.The expression of the thermogenic marker uncoupling protein 1(UCP1)in BAT was determined by RT-qPCR and Western blot to evaluate thermogenic function.RNA sequencing(RNA-seq)was employed to identify differentially expressed genes(DEGs)involved in BAT whitening induced by prolonged continuous light exposure.DEGs were analyzed using the connectivity map(CMap)database to identify potential preventive and therapeutic compounds.The therapeutic efficacy of the selected compounds was subsequently evaluated using the above indicators,and key pathways were validated through western blot analysis.Results:After 5 weeks of continuous light exposure,mice exhibited increased body fat percentage and serum levels of TG,impaired mitochondrial function,reduced thermogenic capacity,and whitening of BAT.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that BAT whitening was primarily associated with the adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,fatty acid metabolism,and circadian rhythm.Ten hub genes identified using Cytoscape were mainly related to AMPK signaling and heat shock proteins.In vivo experiments showed that cordycepin significantly attenuated the increase in body fat percentage caused by prolonged light exposure.This effect was mediated by activation of the AMPK/PGC-1α/UCP1 signaling pathway,which restored the multilocular morphology and thermogenic function of BAT.Conclusion:Cordycepin mitigates continuous light-induced BAT whitening and metabolic disturbances by activating the AMPK signaling pathway.展开更多
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 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.
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 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.
基金supported by the National Science Foundation of China(82202714).
文摘Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
文摘Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and uses new diagnostic parameters related to the"phsse WAvEs of local depolarization".We combined polarization-interferenæregistration with phase scanning of complex amplitude distributions in diffuse Laser speckle fields to detect phase waves of local depolarization in birefringent fibrillar networks of biological tisue and messure their modulation depth.This eppгоsch led to the discovery of new criteria for differentiating verious necrotic changes in diffuse histological samples of myocardial tisue from decmsed individuals with"ischemic heart disase(IHD)--cute coronary insufficiency(ACT)",even in the presænce of a high level of depolarized bckground.To evaluate the degree of necrotic changes in the optical anisotropy of difuse myocardial Layers,a new quantitative parameter--modulation depth of local depolarization wave fluctustions-has been proposed.Using this approsch,for the first time,differentiation of diffuse myocardial samples from decessed individuals with IHD and ACI was achieved witha very good 90.45%and outstanding aocuracy of 95.2%.
基金the National Natural Science Foundation of China(grant no.82272289).
文摘Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distribution and function have gained considerable attention because of their profound impact on metabolic health and overall well-being.Subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)are the two major depots of white adipose tissue,each with distinct roles in metabolism and health.Understanding the characteristics and underlying mechanisms of SAT and VAT is crucial for elucidating the aging process and developing strategies to promote healthy aging.This review focuses on delineating and analyzing the characteristics and intrinsic mechanisms underlying the aging of subcutaneous and visceral adipose tissue during the aging process,which can contribute to a better understanding of the aging process and enhance healthy aging.
基金supported by the Alchemist Project 1415180884(No.20012378,Development of Meta Soft Organ Module Manufacturing Technology without Immunity Rejection and Module Assembly Robot System)funded by the Ministry of Trade,Industry&Energy(MOTIE,Republic of Korea)the Technology Development Program(No.S3318933)funded by the Ministry of SMEs and Startups(MSS,Republic of Korea).
文摘A decellularized extracellular matrix(dECM)constitutes a pivotal biomaterial created by decellularizing the natural extracellular matrix(ECM).This material serves as a supportive medium for intricate cellular interactions,fostering cell growth,differentiation,and organization.However,challenges persist in decellularization,necessitating a balance between preserving the ECM structural integrity and achieving effective cellular removal.An approach to enhancing decellularization involves pre-eliminating unnecessary tissues and effectively reducing final DNA levels to lower than 50 ng/mg ECM on preprocessed tissues.Although this strategic step augments decellularization efficiency,the current manual execution method depends on the operator’s skill.To address this limitation,this study proposed an automated raw tissue slicing system that does not require tissue preparation for slicing.Through carefully controlled tissue applanation pressure and oscillatory incisions with optimized parameters,the system achieved a precision within±10µm in obtaining submillimeter-scale tissue slices of the porcine cornea while avoiding significant microscopic complications in the tissue structure,as observed by tissue histology.These findings suggested the system’s capability to streamline and automate preliminary tissue slicing operations.The efficacy of this approach for decellularization was validated by processing porcine corneas using the proposed system and subsequently decellularizing the processed tissues.DNA level analysis revealed that sliced,subdivided tissues created by this system could expedite DNA reduction even at the initial steps of decellularization,enhancing the overall decellularization procedure.
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
文摘Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
文摘During restorative dental procedures,complete control over the operative site is critical for patient comfort,safety,and the operator’s access and visibility.The success of a fixed prosthesis depends on accurate impression making of the prepared finish lines on the abutment teeth.To optimise long-term outcomes for the fixed restoration,gingival retraction techniques should be used to decrease the marginal discrepancy among the restoration and the prepared abutment.Accurate marginal positioning of the restoration along the prepared finish line of the abutment is essential for therapeutic,preventive,and aesthetic purposes.
基金Open access funding provided by Manipal Academy of Higher Education,Manipal.
文摘Osteoarthritis is a common aging-related disorder that is confined mostly to the chondral layer of joints(e.g., the knee) but can spread to bony layers over time. In its early stages, osteoarthritis has minimal symptoms;however, these gradually worsen over time and include joint pain, stiffness, loss of mobility, and inflammation. The exposed subchondral bone of a Grade 4 osteoarthritic knee is highly prone to erosion if left untreated due to persistent rubbing between the bones, which can lead to painful bone spurs. However, treating osteoarthritis is especially challenging due to the poor mitotic potential and low metabolic activity of chondrocytes. Although currently available tissue-engineered products(e.g., BST-CarGel■, TruFit■, and Atelocollagen■) can achieve structural reconstruction and tissue regeneration, final clinical outcomes can still be improved. Major challenges faced during clinical studies of tissue-engineered constructs include chondrocyte hypertrophy and the development of mechanically inferior fibrous tissue, among others. These issues can be addressed by selecting suitable biomaterial combinations, mimicking the three-dimensional(3D) architecture of the tissue matrix, and better controlling inflammation. Furthermore, it is crucial to generate essential signaling molecules within the articular cartilage ecosystem. This approach must also account for the microarchitecture of the affected joint and support the chondrogenic differentiation of mesenchymal stem cells. The use of tissue-engineered constructs has the potential to overcome each of these challenges, since materials can be modified for drug/biomolecule delivery while simultaneously facilitating the regeneration of robust articular cartilage. Three-dimensional printing has been successfully used in tissue engineering to achieve bioprinting. By manipulating conventional 3D printing techniques and the types of bioink used, many different types of bioprinting have emerged. Overall, these bioprinting techniques can be used to address various challenges associated with osteoarthritis treatment.
基金supported by the National Natural Science Foundation of China(Nos.82122014,82071085,82020108011,and 82301031)the Zhejiang Provincial Natural Science Foundation of China(No.LR21H140001)+2 种基金the National Key Research and Development Program of China(No.2018YFA0703000)the Medical Technology and Education of Zhejiang Province of China(No.2018KY501)the Fundamental Research Funds for the Central Universities(No.2022QZJH55).
文摘Craniofacial muscles are essential components of the skeletal muscular system that contribute to important physiological processes.Severe trauma can induce craniofacial volumetric muscle loss(VML),which impairs muscle regeneration,causes facial muscular deformities and functional disability,and leads to psychosocial consequences such as isolation and depression.Conventional therapies involving muscle flap transposition or autologous tissue grafting achieve morphological repair but are ineffective in restoring muscle function,resulting in donor site injury and sensory deficit.In this study,we successfully constructed a biomimetically engineered muscle tissue that integrates myofiber alignment,effective innervation,and blood perfusion to promote multi-tissue regeneration in the masseter area in vivo,enabling functional regeneration.Using light-controlled micropatterning technology,we constructed mature muscle fibers with oriented alignment and established a neuromuscular co-culture system for in vitro neuromuscular junction reconstruction.Furthermore,we designed and fabricated a vascular network structure to promote tissue vascularization using hydrogel as the vehicle for assembling the composite engineered tissue.Using this technology,the shape and dimension of the constructed entity can be customized to address various muscle defects,enabling individualized repair.This study offers a promising novel strategy for tissue regeneration that breaks through the current challenges in the treatment of craniofacial VML.
基金Supportea by DeNardo Education and Research Foundation GrantJeffrey T.Fort Innovation Fund+3 种基金Siteman Retina Research FundResearch to Prevent Blindness IncGetahun H is supported by Washington University in St.Louis School of Medicine Dean’s Medical Student Research Fellowship for the MD5 Yearlong Research ProgramGetahun H is also a recipient of a Research to Prevent Blindness Medical Student Eye Research Fellowship.
文摘AIM:To evaluate visual outcomes of pars plana vitrectomy(PPV)combined with tissue plasminogen activator(tPA)-induced clot lysis and pneumatic displacement for submacular hemorrhage(SMH)in a cohort of closed-globe trauma patients.METHODS:A retrospective,multicenter interventional case series involving 7 eyes of 7 patients who underwent PPV with subretinal tPA administration for SMH secondary to closed-globe injury were conducted.The primary outcome measure was the change in Snellen visual acuity.RESULTS:The mean age of patients was 32y(range:21-51y),with a mean follow-up duration of 4.6mo(range:1.1-14.9mo).The average best-corrected visual acuity(BCVA)was 20/1020 at baseline and 20/114 at the final visit,respectively(P=0.025).Preoperative BCVA was not a significant predictor of final BCVA(r=0.102,P=0.827).Final BCVA did not differ significantly between patients who underwent PPV within 14d of symptom onset and those who underwent surgery after 14d(P=0.57).All eyes received SF6 or C3F8 gas tamponade.CONCLUSION:Surgical intervention involving tPAmediated clot lysis and pneumatic displacement may yield visual benefits in trauma-induced SMH without underlying retinal vascular disease;however,larger prospective studies are warranted to confirm these findings.
文摘Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuous light exposure.This study aimed to investigate the morphological and functional alterations in BAT under continuous light conditions and to identify traditional Chinese medicine compounds capable of reversing these changes.Methods:A metabolic disorder model was established by subjecting mice to continuous light exposure for 5 weeks.During this period,body weight,food intake,and body fat percentage were monitored.Serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured to assess lipid metabolism.Histological changes in BAT were examined using H&E staining.The expression of the thermogenic marker uncoupling protein 1(UCP1)in BAT was determined by RT-qPCR and Western blot to evaluate thermogenic function.RNA sequencing(RNA-seq)was employed to identify differentially expressed genes(DEGs)involved in BAT whitening induced by prolonged continuous light exposure.DEGs were analyzed using the connectivity map(CMap)database to identify potential preventive and therapeutic compounds.The therapeutic efficacy of the selected compounds was subsequently evaluated using the above indicators,and key pathways were validated through western blot analysis.Results:After 5 weeks of continuous light exposure,mice exhibited increased body fat percentage and serum levels of TG,impaired mitochondrial function,reduced thermogenic capacity,and whitening of BAT.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that BAT whitening was primarily associated with the adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,fatty acid metabolism,and circadian rhythm.Ten hub genes identified using Cytoscape were mainly related to AMPK signaling and heat shock proteins.In vivo experiments showed that cordycepin significantly attenuated the increase in body fat percentage caused by prolonged light exposure.This effect was mediated by activation of the AMPK/PGC-1α/UCP1 signaling pathway,which restored the multilocular morphology and thermogenic function of BAT.Conclusion:Cordycepin mitigates continuous light-induced BAT whitening and metabolic disturbances by activating the AMPK signaling pathway.
