Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessita...Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.展开更多
Limited cells and factors,inadequate mechanical properties,and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds.Herein,we construct a self-oxygenated 3D print...Limited cells and factors,inadequate mechanical properties,and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds.Herein,we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure.The hydrogel scaffold possesses the characteristics of extracellular matrix;Meanwhile,the fabricated hybrid double network structure by polyacrylamide and CaCl_(2)-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability.Furthermore,the O_(2) generated by CaO_(2) nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8,which can significantly promote cell viability and proliferation in vitro,as well as angiogenesis and osteogenic differentiation with the assistance of Zn^(2+).More significantly,the synergy of O_(2) and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need,which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo.Overall,this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.展开更多
Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)suppl...Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)supply oxygen,and(iii)generate reactive oxygen species(ROS;1O2)in response to near-infrared(NIR)laser irradiation.Hb μGels consist of Hb,bovine serum albumin(BSA),chlorin e6(Ce6)and erbium@lutetium upconverting nanoparticles(UCNPs;~35 nm)that effectively convert 808 nm NIR light to 660 nm visible light.These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species(^(1)O_(2))from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity.Moreover,the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme(iron protoporphyrin IX)and display photothermal activity.By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation,it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect.These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.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
基金funded by the National Insti-tutes of Health(No.R01 AR074234)AHA collaborative award(No.944227)the Gillian Reny Stepping Strong Center for Trauma Inno-vation at Brigham and Women's Hospital.
文摘Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.
基金supported by the National Natural Science Foundation of China(NSFC,22172082)NCC Fund(NCC2020FH05)+1 种基金Fundamental Research Funds for the Central Universities,Natural Science Foundation of Tianjin Municipal Science and Technology Commission(2022KJ208)Tianjin Health Science and Technology Project(TJWJ2021QN041).
文摘Limited cells and factors,inadequate mechanical properties,and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds.Herein,we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure.The hydrogel scaffold possesses the characteristics of extracellular matrix;Meanwhile,the fabricated hybrid double network structure by polyacrylamide and CaCl_(2)-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability.Furthermore,the O_(2) generated by CaO_(2) nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8,which can significantly promote cell viability and proliferation in vitro,as well as angiogenesis and osteogenic differentiation with the assistance of Zn^(2+).More significantly,the synergy of O_(2) and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need,which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo.Overall,this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.
基金This work was supported by a National Research Foundation of Korea(NRF)grants funded by the Korean government(No.NRF-2019R1A5A2027340)the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Korean government(MSIT)(No.NRF-2022M3A9G8017220).
文摘Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)supply oxygen,and(iii)generate reactive oxygen species(ROS;1O2)in response to near-infrared(NIR)laser irradiation.Hb μGels consist of Hb,bovine serum albumin(BSA),chlorin e6(Ce6)and erbium@lutetium upconverting nanoparticles(UCNPs;~35 nm)that effectively convert 808 nm NIR light to 660 nm visible light.These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species(^(1)O_(2))from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity.Moreover,the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme(iron protoporphyrin IX)and display photothermal activity.By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation,it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect.These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.
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.
