Sustainable power sources for outdoor wearable electronics are essential for the continuous operation of wearable devices.However,the current lack of engineering design that can harvest energy regardless of weather co...Sustainable power sources for outdoor wearable electronics are essential for the continuous operation of wearable devices.However,the current lack of engineering design that can harvest energy regardless of weather conditions presents a significant challenge.In this regard,this study introduces a wearable,breathable all-weather usable dual energy harvester(AWuDEH)that can seamlessly generate electrical energy regardless of weather conditions.In this study,the AWuDEH integrated with the thermoelectric generator and the droplet-based electricity generator is demonstrated.The AWuDEH,especially engineered with a bi-functional top substrate for radiative cooling and electrification,achieves sustainable energy harvesting outdoors,thereby addressing the conventional challenge associated with the necessity for separate energy harvesters tailored to outdoor usage contingent on weather conditions.The device reaches a maximum power output of 14.6μW cm^(-2)under simulated sunny conditions and generates a much more enhanced thermoelectric power of 74.78μW cm^(-2)and a droplet-based electric power of 256.25 mW m^(-2)in rainy conditions.As proof,this study developed self-powered wearable electronics capable of acquiring physiological signals in simulated outdoor scenarios.This study presents a promising advancement in wearable technology,offering a potent solution for sustainable energy harvesting independent of weather conditions.展开更多
Transparent electro-optical neural interfacing technologies offer simultaneous high-spatial-resolution microscopic imaging,and high-temporal-resolution electrical recording and stimulation.However,fabricating transpar...Transparent electro-optical neural interfacing technologies offer simultaneous high-spatial-resolution microscopic imaging,and high-temporal-resolution electrical recording and stimulation.However,fabricating transparent,flexible,and mechanically robust neural electrodes with high electrochemical performance remains challenging.In this study,we fabricated transparent(72.7%at 570 nm),mechanically robust(0.05%resistance change after 50k bending cycles)ultrathin Au microelectrodes for micro-electrocorticography(µECoG)using a hexadentate metal-polymer ligand bonding with an EDTA/PSS seed layer.These transparentµECoG arrays,fabricated with biocompatible gold,exhibit excellent electrochemical properties(0.73Ω·cm^(2))for neural recording and stimulation with long-term stability.We recorded brain surface waves in vivo,maintaining a low baseline noise and a high signalto-noise ratio during acute and two-week recordings.In addition,we successfully performed optogenetic modulation without light-induced artifacts at 7.32 mW/mm^(2)laser power density.This approach shows great potential for scalable,implantable neural electrodes and wearable optoelectronic devices in digital healthcare systems.展开更多
Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel ...Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel Piezo1 as a key regulator of ILC2 effector function through translational control.Piezo1 is highly expressed in murine and human ILC2s,and its activation by mechanical stress or the Piezo1 agonist,Yoda1 induces calcium influx,triggering mTOR signaling and selectively enhancing IL-13 protein production.Conditional deletion of Piezo1 in ILC2s reduced mTOR activation and puromycin incorporation,leading to impaired protein synthesis and attenuated lung inflammation and fibrosis in the IL-33,Alternaria alternata,and bleomycin models.scRNA-seq and scATAC-seq confirmed that Piezo1-deficient ILC2s retained Il13 transcription and chromatin accessibility but presented translational suppression,as evidenced by protein‒mRNA interactions.Pharmacologic mTOR inhibition phenocopied Piezo1 loss,supporting the functional relevance of the Piezo1–mTOR axis.These findings demonstrate that Piezo1 functions as a mechanosensor that integrates biomechanical cues to regulate cytokine output via mTOR-mediated translation.Targeting Piezo1 signaling or its downstream effectors may provide therapeutic benefits in type 2 inflammation–associated lung diseases.展开更多
Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenar...Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse woundsituations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties andcapacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantagesin wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecularweighthyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging thatcould synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy inthree distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively,these findings underscore the potential of the sHA-CA patch as a promising candidate for the nextgenerationwound dressing.展开更多
In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study...In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study aimed to examine the therapeutic potential of catalase-coated oxygen-generating microparticles embedded in gelatin methacryloyl(cOMP-GelMA)hydrogel to establish an optimized environment conducive to tissue regeneration.Using a large 3×9 cm^(2) rat random-pattern skin flap model,flap survival and regeneration were evaluated across four groups:control,pure GelMA hydrogel,and cOMP-GelMA hydrogel with two concentrations of cOMPs(0.2%and 0.5%w/v).These findings revealed that cOMP-GelMA comprising 0.2%OMP significantly enhanced angiogenesis,arteriogenesis,mitochondrial biogenesis,and antioxidant capacity compared to 0.5%cOMP-GelMA.Furthermore,the alleviation of the inflammatory response was more pronounced at lower cOMP concentrations than at higher concentrations.These results demonstrate that mild hypoxia,facilitated by moderate oxygen delivery,is beneficial for tissue repair and regeneration through peroxisome proliferatoractivated receptor gamma coactivator 1-alpha-and hypoxia-inducible factor 1-alpha-dependent signaling pathways.This study highlights the innovative aspect of using a large-scale model to explore the therapeutic benefits of mild hypoxia and suggests that controlled oxygen delivery by cOMPs can improve the long-term functional recovery of ischemic tissues.展开更多
Lipid-coated microbubbles are widely used as an ultrasound contrast agent,as well as drug delivery carriers.However,the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short h...Lipid-coated microbubbles are widely used as an ultrasound contrast agent,as well as drug delivery carriers.However,the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system,and the difficulty of surface modification of microbubbles for active targeting.The exosome,a type of extracellular vesicle,has a preferentially targeting ability for its original cell.In this study,exosome-fused microbubbles(Exo-MBs)were developed by embedding the exosome membrane proteins into microbubbles.As a result,the stability of Exo-MBs is improved over the conventional microbubbles.On the same principle that under the exposure of ultrasound,microbubbles are cavitated and self-assembled into nano-sized particles,and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles(Exo-NPs).The Exo-NPs showed favorable targeting properties to their original cells.A photosensitizer,chlorin e6,was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier.Much higher therapeutic efficacy of photodynamic therapy was confirmed,followed by cancer immunotherapy from immunogenic cell death.We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.展开更多
Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in co...Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in conjunction with stem cells and growth factors,have been developed to mimic the respective layers for osteochondral defect repair.In this study,we designed a hyaline cartilage-hypertrophic cartilage bilayer graft(RGD/RGDW)with chondrocytes.Previously,we demonstrated that RGD peptide-modified chondroitin sulfate cryogel(RGD group)is chondro-conductive and capable of hyaline cartilage formation.Here,we incorporated whitlockite(WH),a Mg^(2+)-containing calcium phosphate,into RGD cryogel(RGDW group)to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage.This is the first study to use WH to produce hypertrophic cartilage.Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo,which mineralized into calcified cartilage in bone microenvironment.Subsequently,RGD cryogel and RGDW cryogel were combined into bilayer(RGD/RGDW group)and implanted into rabbit osteochondral defect,where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation.While the RGD group(monolayer)formed hyaline-like neotissue that extends into the subchondral bone,the RGD/RGDW group(bilayer)regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.展开更多
基金supported by the National Research Foundation of Korea(NRF)(RS-2024-00343512,RS-2024-00416938).
文摘Sustainable power sources for outdoor wearable electronics are essential for the continuous operation of wearable devices.However,the current lack of engineering design that can harvest energy regardless of weather conditions presents a significant challenge.In this regard,this study introduces a wearable,breathable all-weather usable dual energy harvester(AWuDEH)that can seamlessly generate electrical energy regardless of weather conditions.In this study,the AWuDEH integrated with the thermoelectric generator and the droplet-based electricity generator is demonstrated.The AWuDEH,especially engineered with a bi-functional top substrate for radiative cooling and electrification,achieves sustainable energy harvesting outdoors,thereby addressing the conventional challenge associated with the necessity for separate energy harvesters tailored to outdoor usage contingent on weather conditions.The device reaches a maximum power output of 14.6μW cm^(-2)under simulated sunny conditions and generates a much more enhanced thermoelectric power of 74.78μW cm^(-2)and a droplet-based electric power of 256.25 mW m^(-2)in rainy conditions.As proof,this study developed self-powered wearable electronics capable of acquiring physiological signals in simulated outdoor scenarios.This study presents a promising advancement in wearable technology,offering a potent solution for sustainable energy harvesting independent of weather conditions.
基金supported in part by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2022-NR069917,RS-2024-00416319)in part by the‘DGIST intramural grant’(25-IRJoint-03)+1 种基金in part by an Ideas Grant from the National Health and Medical Research Council(NHMRC)of Australia(APP1188414)in part by the Interdisciplinary Research Initiatives Program from College of Engineering and College of Medicine,Seoul National University(grant no.800-20240490).
文摘Transparent electro-optical neural interfacing technologies offer simultaneous high-spatial-resolution microscopic imaging,and high-temporal-resolution electrical recording and stimulation.However,fabricating transparent,flexible,and mechanically robust neural electrodes with high electrochemical performance remains challenging.In this study,we fabricated transparent(72.7%at 570 nm),mechanically robust(0.05%resistance change after 50k bending cycles)ultrathin Au microelectrodes for micro-electrocorticography(µECoG)using a hexadentate metal-polymer ligand bonding with an EDTA/PSS seed layer.These transparentµECoG arrays,fabricated with biocompatible gold,exhibit excellent electrochemical properties(0.73Ω·cm^(2))for neural recording and stimulation with long-term stability.We recorded brain surface waves in vivo,maintaining a low baseline noise and a high signalto-noise ratio during acute and two-week recordings.In addition,we successfully performed optogenetic modulation without light-induced artifacts at 7.32 mW/mm^(2)laser power density.This approach shows great potential for scalable,implantable neural electrodes and wearable optoelectronic devices in digital healthcare systems.
基金supported by the National Research Foundation of Korea(2022R1A2C3007730,2021M3A9I2080493 and RS-2023-00217798)the Korea-US Collaborative Research Fund(RS-2024-00468455)funded by the Ministry of Science and ICT and the Ministry of Health&Welfare,Republic of Korea.
文摘Group 2 innate lymphoid cells(ILC2s)are central effectors of type 2 immune responses in the lung;however,how mechanical cues regulate their function remains unclear.Here,we identified the mechanosensitive ion channel Piezo1 as a key regulator of ILC2 effector function through translational control.Piezo1 is highly expressed in murine and human ILC2s,and its activation by mechanical stress or the Piezo1 agonist,Yoda1 induces calcium influx,triggering mTOR signaling and selectively enhancing IL-13 protein production.Conditional deletion of Piezo1 in ILC2s reduced mTOR activation and puromycin incorporation,leading to impaired protein synthesis and attenuated lung inflammation and fibrosis in the IL-33,Alternaria alternata,and bleomycin models.scRNA-seq and scATAC-seq confirmed that Piezo1-deficient ILC2s retained Il13 transcription and chromatin accessibility but presented translational suppression,as evidenced by protein‒mRNA interactions.Pharmacologic mTOR inhibition phenocopied Piezo1 loss,supporting the functional relevance of the Piezo1–mTOR axis.These findings demonstrate that Piezo1 functions as a mechanosensor that integrates biomechanical cues to regulate cytokine output via mTOR-mediated translation.Targeting Piezo1 signaling or its downstream effectors may provide therapeutic benefits in type 2 inflammation–associated lung diseases.
基金support from the Ministry of Science and ICT of Korea(NRF-2021R1A2C2008821 and 2022H1D3A2A02093385)the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean government(21A0301L1-21)The Institute of Engineering Research at Seoul National University provided research facilities,and additional support came from the SNU Engineering-Medicine Collaboration grant.
文摘Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse woundsituations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties andcapacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantagesin wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecularweighthyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging thatcould synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy inthree distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively,these findings underscore the potential of the sHA-CA patch as a promising candidate for the nextgenerationwound dressing.
基金supported by a multidisciplinary research grant-in-aid from the Seoul Metropolitan Government Seoul National University(SMG-SNU)Boramae Medical Center(04-2023-0044)&SNU,Bio-MAX Institutea focused clinical research grant-in-aid from the Seoul Metropolitan GovernmentSeoul National University(SMG-SNU)Boramae Medical Center(04-2024-0017)+4 种基金a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(RS-2023-00213423 and RS-2024-00341578)a Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean government(Ministry of Science and ICT,Ministry of Health&Welfare23A0202L1)funded by the National Institutes of Health(R01AR074234 and R01AR077132)AHA Collaborative Award(944227).
文摘In regenerative medicine,effective management of tissue ischemia in surgical skin flaps is crucial,yet chal-lenging,particularly because inadequate blood flow often leads to necrosis at the distal flap tips.This study aimed to examine the therapeutic potential of catalase-coated oxygen-generating microparticles embedded in gelatin methacryloyl(cOMP-GelMA)hydrogel to establish an optimized environment conducive to tissue regeneration.Using a large 3×9 cm^(2) rat random-pattern skin flap model,flap survival and regeneration were evaluated across four groups:control,pure GelMA hydrogel,and cOMP-GelMA hydrogel with two concentrations of cOMPs(0.2%and 0.5%w/v).These findings revealed that cOMP-GelMA comprising 0.2%OMP significantly enhanced angiogenesis,arteriogenesis,mitochondrial biogenesis,and antioxidant capacity compared to 0.5%cOMP-GelMA.Furthermore,the alleviation of the inflammatory response was more pronounced at lower cOMP concentrations than at higher concentrations.These results demonstrate that mild hypoxia,facilitated by moderate oxygen delivery,is beneficial for tissue repair and regeneration through peroxisome proliferatoractivated receptor gamma coactivator 1-alpha-and hypoxia-inducible factor 1-alpha-dependent signaling pathways.This study highlights the innovative aspect of using a large-scale model to explore the therapeutic benefits of mild hypoxia and suggests that controlled oxygen delivery by cOMPs can improve the long-term functional recovery of ischemic tissues.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science,and Technology(NRF-2016R1A6A1A03012845,NRF-2022M3E5F1017553),Republic of Koreathe Ministry of Food and Drug Safety grant(22213MFDS421),Republic of Korea.
文摘Lipid-coated microbubbles are widely used as an ultrasound contrast agent,as well as drug delivery carriers.However,the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system,and the difficulty of surface modification of microbubbles for active targeting.The exosome,a type of extracellular vesicle,has a preferentially targeting ability for its original cell.In this study,exosome-fused microbubbles(Exo-MBs)were developed by embedding the exosome membrane proteins into microbubbles.As a result,the stability of Exo-MBs is improved over the conventional microbubbles.On the same principle that under the exposure of ultrasound,microbubbles are cavitated and self-assembled into nano-sized particles,and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles(Exo-NPs).The Exo-NPs showed favorable targeting properties to their original cells.A photosensitizer,chlorin e6,was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier.Much higher therapeutic efficacy of photodynamic therapy was confirmed,followed by cancer immunotherapy from immunogenic cell death.We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(NRF-2021K1A3A1A57086407,NRF-2021R1A2C2008821,NRF-2022R1I1A1A01071991)Arun Kumar Rajendran was supported by the National Research Foundation of Korea(NRF)grant Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea(2020H1D3A1A04081286)The Institute of Engineering Research at Seoul National University provided research facilities,and additional support came from the SNU Engineering-Medicine Collaboration grant.
文摘Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface.Multilayered or gradient scaffolds,often in conjunction with stem cells and growth factors,have been developed to mimic the respective layers for osteochondral defect repair.In this study,we designed a hyaline cartilage-hypertrophic cartilage bilayer graft(RGD/RGDW)with chondrocytes.Previously,we demonstrated that RGD peptide-modified chondroitin sulfate cryogel(RGD group)is chondro-conductive and capable of hyaline cartilage formation.Here,we incorporated whitlockite(WH),a Mg^(2+)-containing calcium phosphate,into RGD cryogel(RGDW group)to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage.This is the first study to use WH to produce hypertrophic cartilage.Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo,which mineralized into calcified cartilage in bone microenvironment.Subsequently,RGD cryogel and RGDW cryogel were combined into bilayer(RGD/RGDW group)and implanted into rabbit osteochondral defect,where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation.While the RGD group(monolayer)formed hyaline-like neotissue that extends into the subchondral bone,the RGD/RGDW group(bilayer)regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.