The monodisperse Au@Ag bimetallic nanorod is encapsulated by crosslinked poly( N-isopropylacrylamide)( PNIPAM) to produce thermo-responsive composite microgel with well-defined core-shell structure( Au@ Ag NR@ PNIPAM ...The monodisperse Au@Ag bimetallic nanorod is encapsulated by crosslinked poly( N-isopropylacrylamide)( PNIPAM) to produce thermo-responsive composite microgel with well-defined core-shell structure( Au@ Ag NR@ PNIPAM microgel)by seed-precipitation polymerization method using butenoic acid modified Au @ Ag NRs as seeds. When the temperature of the aqueous medium increases from 20℃ to 50℃,the localized surface plasmon resonance( LSPR) band of the entrapped Au @ Ag NR is pronouncedly red-shifted because of the decreased spatial distances between them as a result of shrinkage of the microgels,leading to their plasmonic coupling. The temperature tunable plasmonic coupling is demonstrated by temperature dependence of the surface enhanced Raman spectroscopy( SERS) signal of 1-naphthol in aqueous solution. Different from static plasmonic coupling modes from nanostructured assembly or array system of noble metals,the proposed plasmonic coupling can be dynamically controlled by environmental temperature. Therefore, the thermo responsive hybrid microgels have potential applications in mobile LSPR or SERS microsensors for living tissues or cells.展开更多
Droplet based microfluidic is an effective, versatile and scalable approach which can be used to produce structured microgels with desirable features. The high degree of control endowed with microfluidics enables the ...Droplet based microfluidic is an effective, versatile and scalable approach which can be used to produce structured microgels with desirable features. The high degree of control endowed with microfluidics enables the formation of various functional microgels such as multicompartment encapsulations, Janus shaped particles and non spherical microgels. These microgels have aroused great interest in biological engineering aspect, since they outperform their counterparts produced from other techniques and have been applied in drug delivery, 3 Dimensional cell culture, micro tissues, single cell assay, tissue engineering and bioimaging. In this review, we will summarize the fabrication processes, technology comparisons and the usages in biomedical applications.展开更多
The factors affecting particle size of reactive microgels formed during the self-emulsifying copolymerization of unsaturated polyester (UP)with butyl acrylate (BA)have been studied. The parameters discussed are: the p...The factors affecting particle size of reactive microgels formed during the self-emulsifying copolymerization of unsaturated polyester (UP)with butyl acrylate (BA)have been studied. The parameters discussed are: the proportion of the UP in the monomer mixture, the molecular weight and the carboxyl value of the UP, the phase ratio, the electrolyte concentration and the polar solvent additive. The seeding emulsion polymerization is discussed as well.It turned out that the particle size of the reactive microgels can be controlled in a definite range by changing the experimental conditions. However the particle size distribution becomes broader as the average diameter increases. It is suggested that the agglomeration of primary particles plays an important role during the growth of microgel particle.展开更多
Fluorescent poly(N-isopropylacrylamide-co-Nile blue)(pNIPAm-co-NB)microgels were synthesized that exhibited fluorescence intensity changes in a water temperature-dependent fashion.NB is well known to exhibit fluoresce...Fluorescent poly(N-isopropylacrylamide-co-Nile blue)(pNIPAm-co-NB)microgels were synthesized that exhibited fluorescence intensity changes in a water temperature-dependent fashion.NB is well known to exhibit fluorescence intensity that depends on the hydrophobicity of the environment,while pNIPAm-based microgels are well known to transition from swollen(hydrophilic)to collapsed(relatively hydrophobic)at temperatures greater than 32℃;hence,we attribute the above behavior to the hydrophobicity changes of the microgels with increasing temperature.This phenomenon is ultimately due to NB dimers(relatively quenched fluorescence)being broken in the hydrophobic environment of the microgels leading to relatively enhanced fluorescence.We went on to show that the introduction of cucurbit[7]uril(CB[7])into the pNIPAm-co-NB microgels enhanced their fluorescence allowing them to be used for polyamine(e.g.,spermine[SPM])detection.Specifically,CB[7]forms a host–guest interaction with NB in the microgels,which prevents NB dimerization and enhances their fluorescence.When SPM is present,it forms a host–guest complex that is favored over the CB[7]-NB host–guest interaction,which frees the NB for dimerization and leads to fluorescence quenching.As a result,we could generate an SPM sensor capable of SPM detection down to~0.5µmol/L in complicated matrixes such as serum and urine.展开更多
MXene nanomaterials are one of the most promising electrode material candidates for supercapacitors owing to their high conductivity,abundant surface functional groups and large surface area.However,electrodes based o...MXene nanomaterials are one of the most promising electrode material candidates for supercapacitors owing to their high conductivity,abundant surface functional groups and large surface area.However,electrodes based on MXene may result in low ion-accessible surface area and blocked ion transport pathways because of the self-restacking of MXene nanosheets.It is essential to suppress the self-res tacking of nanosheets and increase the electrochemical active sites in order to optimize the electrode.In this work,bidirectionally aligned MXene hybrid aerogel(A-MHA)assembled with MXene nanosheets and microgels is prepared using a facile bidirectional freeze casting and freeze-drying method.The bidirectionally aligned structure together with the three-dimensional structured microgels in the A-MHAs,can improve the ionaccessible surface area and provide more barrier-free channels by exposing more active sites and ensuring electrolyte transport freely.The A-MHA with MXene microgels content of 40 wt%exhibits a high specific capacitance of 760 F·g^(-1)at 1 A·g^(-1)and a remarkable cyclic performance of 97%after 10,000 cycles at100 mV·s^(-1)in 1 mol·L^(-1)H_(2)SO_(4)electrolyte.A-MHAs show remarkable electrochemical properties and are of potential application in energy storage.展开更多
Lead(Ⅱ)(Pb2+)ions are toxic heavy metal ions that can accumulate in the human body through water and cause severe health problems,including neurotoxicity,nephrotoxicity,hematological toxicity and even genotoxicity ef...Lead(Ⅱ)(Pb2+)ions are toxic heavy metal ions that can accumulate in the human body through water and cause severe health problems,including neurotoxicity,nephrotoxicity,hematological toxicity and even genotoxicity effects.To remove Pb2+selectively and effectively from aqueous solutions,we develop a novel type of Pb2+-recognizable microgels with excellent adsorption capacity to Pb2+,which are fabri-cated from 4-acrylamidobenzo-18-crown-6(B18C6Am)and N-isopropylmethacrylamide(NIPMAM)monomers by precipitation copolymerization method.The prepared poly(N-isopropylmethacrylamide-co-4-acrylamidobenzo-18-crown-6)(PNMB)microgels exhibit expanded structures,because the electron-donating methyl groups atα-carbon could descend the polarity of C=O in the NIPMAM monomers and thus weaken the polymer segment…segment interactions.The expanded structures of PNMB microgels are beneficial for adsorption of Pb2+due to the low steric hindrance in the polymeric networks.The Pb2+adsorption isotherms of PNMB microgels are consistent with the Langmuir model for monolayer adsorption.The results indicate that the prepared Pb2+-recognizable PNMB microgels are highly promising for the selective removal of lead(Ⅱ)ions from aqueous solutions.展开更多
Synovial fluid is made up of various biomacromolecules,including hyaluronic acid,aggrecans,lubricins,and phosphatidylcholine lipid,which are assembled onto the surface of articular cartilage in a gel state.Among them,...Synovial fluid is made up of various biomacromolecules,including hyaluronic acid,aggrecans,lubricins,and phosphatidylcholine lipid,which are assembled onto the surface of articular cartilage in a gel state.Among them,brush-like biomacromolecules or assemblies have a vital effect on human joint lubrication.Inspired by this,the combination of brush-like molecular structures and gel-like assembly may be an efficient approach for the synthesis of biomimetic lubricating matters.Learning from the lubrication system of human joints,poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)brushes grafted poly(N-isopropylacrylamide-co-acrylic acid)(poly(NIPAAm-co-AA))microgels,abbreviated as MBs-g-MGs,were synthesized as one kind of biomimetic lubricating additives.It is worth noting that this bionic strategy considered both molecular structure and assembled form,which enabled this hairy microgel to achieve low friction in aqueous medium.Meanwhile,the effective lubrication was still achieved when using MBs-g-MGs at high temperature,indicating that this microgel maintains a good lubricating effect over a wide range of temperature.In addition,this kind of microgel possessed good biocompatibility,which laid the foundation for potential biomedical applications.Looking beyond,these biomimetic microgels may provide an effective lubricating effect for water-based sliding interfaces,especially in biomedical systems.展开更多
The research and application of responsive materials have long been hampered by their complicated designs and tedious construction processes.Besides,many current responsive materials show retard or weak responsiveness...The research and application of responsive materials have long been hampered by their complicated designs and tedious construction processes.Besides,many current responsive materials show retard or weak responsiveness.In this study,responsive hybrid poly(vinyl alcohol)hydrogel membranes with embedded poly(N-isopropylacrylamide-acrylic acid)microgels as valves were constructed by simple mixing and subsequent freezing-thawing process.In the structure of the membranes,the matrix poly(vinyl alcohol)chains thread through and entangle with the microgels,and the microgels are firmly constrained within the hybrid hydrogel network.The fast and sharp temperature responsiveness of the embedded microgels was largely retained and endowed the hydrogel membrane with excellent temperature and pH responsiveness.Moreover,the hydrogel membrane showed excellent fatigue resistance in both temperature and pH-responsive flux examination.This study presented the great potential of these hybrid hydrogel membranes in biomedical applications and provided a new strategy for the future design and construction of responsive biomaterials.展开更多
The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dim...The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and protection.In this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner.After gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from GelMA.The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell viability.The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion.Furthermore,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials distribution.Overall,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.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
Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, imm...Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, immunoadjuvant, and immune checkpoint inhibitor is presented by microfluidic electrospray technology and liquid nitrogen treatment. Owing to the encapsulation of cryo-shocked cancer cells and immunoadjuvant, the microgels can recruit dendritic cells and activate them in situ, and evoke a robust immune response. Moreover, with the combination of the immune checkpoint inhibitor, the antitumor immune response is further enhanced by inhibiting the interaction of PD1 and PDL1. With this, the excellent anti-recurrence and anti-metastasis efficacy of the microgels are demonstrated in an orthotopic breast cancer mouse model. Besides, because of the excellent biocompatibility and appropriate degradation performance, the microgels can provide support for normal cell adhesion and growth, which is beneficial to tissue reconstruction. These properties indicate the great value of the cryo-shocked cancer cell microgels for efficient tumor postoperative combination immunotherapy and tissue regeneration.展开更多
The tribological behavior of 316L stainless steel/CoCrMo alloy contacts under aqueous lubrication was investigated in this work.Three types of microgels including poly(N-isopropylacrylamide)(PNIPAM),polyacrylic acid(P...The tribological behavior of 316L stainless steel/CoCrMo alloy contacts under aqueous lubrication was investigated in this work.Three types of microgels including poly(N-isopropylacrylamide)(PNIPAM),polyacrylic acid(PAA),and poly(N-isopropylacrylamide-co-acrylic acid)(PNIPAM-co-PAA)were prepared and used as lubricant additives in aqueous solutions.Tribological tests were conducted using a ball-on-disk reciprocating tribometer,over a range of temperatures,pH,and concentrations of the microgels.The PNIPAM-co-PAA microgels were proven to have excellent anti-friction and anti-wear properties,depending on the temperature and pH values of the solutions.The maximum friction coefficient coincided with the lower critical solution temperature of the PNIPAM-co-PAA microgels at 32°C.At the same time,the friction coefficient increased with the increase in pH value of the lubricant solution with the PNIPAM-co-PAA microgels.The unique thermal-and pH-sensitive properties of the PNIPAM-co-PAA microgels provided a new strategy for controlling the friction and wear of steel/CoCrMo alloy contacts under aqueous lubrication.展开更多
Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to trans...Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.展开更多
Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaf...Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.展开更多
Diabetes is a serious public health problem affecting 422 million people worldwide. Traditional diabetes management often requires multiple daily insulin injections, associated with pain and inadequate glycemia contro...Diabetes is a serious public health problem affecting 422 million people worldwide. Traditional diabetes management often requires multiple daily insulin injections, associated with pain and inadequate glycemia control. Herein, we have developed an ultrasound-triggered insulin delivery system capable of pulsatile insulin release that can provide both long-term sustained and fast on-demand responses. In this system, insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsules are encapsulated within chitosan microgels. The encapsulated insulin in nanocapsules can passively diffuse from the nanoparticle but remain restricted within the microgel. Upon ultrasound treatment, the stored insulin in microgels can be rapidly released to regulate blood glucose levels. In a chemically-induced type 1 diabetic mouse model, we demonstrated that this system, when activated by 30 s ultrasound administration, could effectively achieve glycemic control for up to one week in a noninvasive, localized, and pulsatile manner.展开更多
Microgels with a thermo-sensitive poly(N-isopropylacrylamide)(polyNIPAm) backbone and bis-imidazolium(VIM) ionic cross-links, denoted as poly(NIPAm-co-VIM), were successfully prepared. The as-synthesized ionic microge...Microgels with a thermo-sensitive poly(N-isopropylacrylamide)(polyNIPAm) backbone and bis-imidazolium(VIM) ionic cross-links, denoted as poly(NIPAm-co-VIM), were successfully prepared. The as-synthesized ionic microgels were converted to nanoreactors, denoted as Au@PNI MGs, upon generation and immobilization of gold nanoparticles(Au NPs) of 5–8 nm in size into poly(NIPAm-co-VIM). The content of Au NPs in microgels could be regulated by controlling the 1,6-dibromohexane/vinylimidazole molar ratio in the quaternization reaction. The microgel-based nanoreactors were morphologically spherical and uniform in size, and presented reversible thermo-sensitive behavior with volume phase transition temperatures(VPTTs) at 39–40 °C. The Au@PNI MGs were used for the reduction of 4-nitrophenol, of which the catalytic activity could be modulated by temperature.展开更多
Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)....Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2.Methods In this study,a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein(S protein)in human saliva.The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid,and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication.The electrochemical performance of the sensor was evaluated through differential pulse voltammetry.Results Under optimal experimental conditions,the linear range of the sensor was 10-13-10-9 mg/m L,whereas the detection limit was 9.55 fg/mL.Furthermore,the S protein was instilled in artificial saliva as the infected human saliva model,and the sensing platform showed satisfactory detection capability.Conclusion The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein,indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.展开更多
Injecting CO_(2)into the underground for oil displacement and shortage is an important technique for carbon capture,utilization and storage(CCUS).One of the main problems during the CO_(2)injection is the channeling p...Injecting CO_(2)into the underground for oil displacement and shortage is an important technique for carbon capture,utilization and storage(CCUS).One of the main problems during the CO_(2)injection is the channeling plugging.Finding an effective method for the gas channeling plugging is a critical issue in the CO_(2)EOR process.In this work,an acid-resistance microgel named dispersed particle gel(DPG)was characterized and its stability was tested in the CO_(2)environment.The microgel size selection strategies for the homogeneous and heterogeneous reservoirs were respectively investigated using the single core flooding and three parallel core flooding experiments.Moreover,the comparison of microgel alternate CO_(2)(MAC)injection and water alternate CO_(2)(WAC)injection in the dual core flooding experiments were presented for the investigation of the role of microgel on the conformance control in CO_(2)flooding process.The results have shown that the microgel featured with ANH and CAN groups can keep its morphology after aging 7 days in the CO_(2)environment.Where,the small microgel with unobstructed migration and large microgel with good plugging efficiency for the high permeability zone were respectively featured with the higher recovery factor in homogeneous and heterogeneous conditions,which indicate they are preferred used for the oil displacement and conformance control.Compared to WAC injection,MAC injection had a higher incremental recovery factor of 12.4%.It suggests the acid-resistance microgel would be a good candidate for the conformance control during CO_(2)flooding process.展开更多
While deployment of intracoronary stents has been shown to reduce restenosis, stenting can also damage the endothelial monolayer lining the vessel wall, leading to possible in-stent thrombosis. Local drug delivery fro...While deployment of intracoronary stents has been shown to reduce restenosis, stenting can also damage the endothelial monolayer lining the vessel wall, leading to possible in-stent thrombosis. Local drug delivery from stent surfaces represents a means of delivering therapeutic doses of drug directly to the target site. The aim of this study was to elute fluvastatin, which can inhibit vascular smooth muscle cell proliferation, and xemilofiban, which prevents platelet adhesion and aggregation, together in bioactive concentrations from the same copolymer system. Combined elution from thermoresponsive N-isopropylacrylamide (NiPAAm)/N-tert-butylacrylamide (NtBAAm)-derived copolymer systems was achieved using microgels (NiPAAm/NtBAAm 65/35 wt/wt) randomly dispersed in 85/15 matrices. Fluvastatin elution from 5 mm films over a 14-day period showed initial burst release, which leveled off. Of the total incorporated (8.33 ± 0.21 nmol, n=4), 68.5 % was eluted during this period. Xemilofiban release was measured in terms of its ability to inhibit platelet adhesion, using a microfluidic system. To investigate the influence of location and hydrophobicity on elution of bioactivity, three separate systems were employed. While elution of anti-adhesive activity from the system containing xemilofiban-loaded matrices was more dramatic in the short term, a more sustained level of inhibition was achieved when xemilofiban had been incorporated into microgels. All samples investigated for anti-adhesive activity also decreased human coronary artery smooth muscle cell proliferation. Therefore xemilofiban has potential as an agent for preventing in-stent thrombosis. Our study has demonstrated the feasibility of using this novel matrix/microgel system to regulate simultaneous release of both agents in bioactive concentrations.展开更多
Three-dimensional(3D)bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions.However,the dense hydrogel networks that form after the gelation of...Three-dimensional(3D)bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions.However,the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated cells.Herein,a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks(MPNs)for enhancing nutrient delivery and cell growth.The sacrificial microgel-laden bioink,which contains cell/gelatin methacryloyl(GelMA)mixture and gelled gelatin microgel,is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold platform.Then,the construct is permanently stabilized through photo-crosslinking of GelMA.The MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin microgel.These MPNs allowed for effective oxygen/nutrient diffusion,facilitating the generation of bioactive tissues.Specifically,osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs(≥1 cm)with MPNs showed enhanced bioactivity during culture.The 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.展开更多
基金National Natural Science Foundation of China(No.51373030)Chinese Universities Scientific Fund(No.CUSF-DH-D-2014023)
文摘The monodisperse Au@Ag bimetallic nanorod is encapsulated by crosslinked poly( N-isopropylacrylamide)( PNIPAM) to produce thermo-responsive composite microgel with well-defined core-shell structure( Au@ Ag NR@ PNIPAM microgel)by seed-precipitation polymerization method using butenoic acid modified Au @ Ag NRs as seeds. When the temperature of the aqueous medium increases from 20℃ to 50℃,the localized surface plasmon resonance( LSPR) band of the entrapped Au @ Ag NR is pronouncedly red-shifted because of the decreased spatial distances between them as a result of shrinkage of the microgels,leading to their plasmonic coupling. The temperature tunable plasmonic coupling is demonstrated by temperature dependence of the surface enhanced Raman spectroscopy( SERS) signal of 1-naphthol in aqueous solution. Different from static plasmonic coupling modes from nanostructured assembly or array system of noble metals,the proposed plasmonic coupling can be dynamically controlled by environmental temperature. Therefore, the thermo responsive hybrid microgels have potential applications in mobile LSPR or SERS microsensors for living tissues or cells.
文摘Droplet based microfluidic is an effective, versatile and scalable approach which can be used to produce structured microgels with desirable features. The high degree of control endowed with microfluidics enables the formation of various functional microgels such as multicompartment encapsulations, Janus shaped particles and non spherical microgels. These microgels have aroused great interest in biological engineering aspect, since they outperform their counterparts produced from other techniques and have been applied in drug delivery, 3 Dimensional cell culture, micro tissues, single cell assay, tissue engineering and bioimaging. In this review, we will summarize the fabrication processes, technology comparisons and the usages in biomedical applications.
文摘The factors affecting particle size of reactive microgels formed during the self-emulsifying copolymerization of unsaturated polyester (UP)with butyl acrylate (BA)have been studied. The parameters discussed are: the proportion of the UP in the monomer mixture, the molecular weight and the carboxyl value of the UP, the phase ratio, the electrolyte concentration and the polar solvent additive. The seeding emulsion polymerization is discussed as well.It turned out that the particle size of the reactive microgels can be controlled in a definite range by changing the experimental conditions. However the particle size distribution becomes broader as the average diameter increases. It is suggested that the agglomeration of primary particles plays an important role during the growth of microgel particle.
文摘Fluorescent poly(N-isopropylacrylamide-co-Nile blue)(pNIPAm-co-NB)microgels were synthesized that exhibited fluorescence intensity changes in a water temperature-dependent fashion.NB is well known to exhibit fluorescence intensity that depends on the hydrophobicity of the environment,while pNIPAm-based microgels are well known to transition from swollen(hydrophilic)to collapsed(relatively hydrophobic)at temperatures greater than 32℃;hence,we attribute the above behavior to the hydrophobicity changes of the microgels with increasing temperature.This phenomenon is ultimately due to NB dimers(relatively quenched fluorescence)being broken in the hydrophobic environment of the microgels leading to relatively enhanced fluorescence.We went on to show that the introduction of cucurbit[7]uril(CB[7])into the pNIPAm-co-NB microgels enhanced their fluorescence allowing them to be used for polyamine(e.g.,spermine[SPM])detection.Specifically,CB[7]forms a host–guest interaction with NB in the microgels,which prevents NB dimerization and enhances their fluorescence.When SPM is present,it forms a host–guest complex that is favored over the CB[7]-NB host–guest interaction,which frees the NB for dimerization and leads to fluorescence quenching.As a result,we could generate an SPM sensor capable of SPM detection down to~0.5µmol/L in complicated matrixes such as serum and urine.
基金financially supported by the National Natural Science Foundation of China(No.52002354)China Postdoctoral Science Foundation(No.2020M672256)。
文摘MXene nanomaterials are one of the most promising electrode material candidates for supercapacitors owing to their high conductivity,abundant surface functional groups and large surface area.However,electrodes based on MXene may result in low ion-accessible surface area and blocked ion transport pathways because of the self-restacking of MXene nanosheets.It is essential to suppress the self-res tacking of nanosheets and increase the electrochemical active sites in order to optimize the electrode.In this work,bidirectionally aligned MXene hybrid aerogel(A-MHA)assembled with MXene nanosheets and microgels is prepared using a facile bidirectional freeze casting and freeze-drying method.The bidirectionally aligned structure together with the three-dimensional structured microgels in the A-MHAs,can improve the ionaccessible surface area and provide more barrier-free channels by exposing more active sites and ensuring electrolyte transport freely.The A-MHA with MXene microgels content of 40 wt%exhibits a high specific capacitance of 760 F·g^(-1)at 1 A·g^(-1)and a remarkable cyclic performance of 97%after 10,000 cycles at100 mV·s^(-1)in 1 mol·L^(-1)H_(2)SO_(4)electrolyte.A-MHAs show remarkable electrochemical properties and are of potential application in energy storage.
基金support from the National Natural Science Foundation of China(grant Nos.21991101,22022810).
文摘Lead(Ⅱ)(Pb2+)ions are toxic heavy metal ions that can accumulate in the human body through water and cause severe health problems,including neurotoxicity,nephrotoxicity,hematological toxicity and even genotoxicity effects.To remove Pb2+selectively and effectively from aqueous solutions,we develop a novel type of Pb2+-recognizable microgels with excellent adsorption capacity to Pb2+,which are fabri-cated from 4-acrylamidobenzo-18-crown-6(B18C6Am)and N-isopropylmethacrylamide(NIPMAM)monomers by precipitation copolymerization method.The prepared poly(N-isopropylmethacrylamide-co-4-acrylamidobenzo-18-crown-6)(PNMB)microgels exhibit expanded structures,because the electron-donating methyl groups atα-carbon could descend the polarity of C=O in the NIPMAM monomers and thus weaken the polymer segment…segment interactions.The expanded structures of PNMB microgels are beneficial for adsorption of Pb2+due to the low steric hindrance in the polymeric networks.The Pb2+adsorption isotherms of PNMB microgels are consistent with the Langmuir model for monolayer adsorption.The results indicate that the prepared Pb2+-recognizable PNMB microgels are highly promising for the selective removal of lead(Ⅱ)ions from aqueous solutions.
基金financial support from the National Natural Science Foundation of China(Nos.51905433 and 52175187)the China Postdoctoral Science Foundation(No.2021M692625)the Fundamental Research Funds for the Central Universities(No.3102019JC001).
文摘Synovial fluid is made up of various biomacromolecules,including hyaluronic acid,aggrecans,lubricins,and phosphatidylcholine lipid,which are assembled onto the surface of articular cartilage in a gel state.Among them,brush-like biomacromolecules or assemblies have a vital effect on human joint lubrication.Inspired by this,the combination of brush-like molecular structures and gel-like assembly may be an efficient approach for the synthesis of biomimetic lubricating matters.Learning from the lubrication system of human joints,poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)brushes grafted poly(N-isopropylacrylamide-co-acrylic acid)(poly(NIPAAm-co-AA))microgels,abbreviated as MBs-g-MGs,were synthesized as one kind of biomimetic lubricating additives.It is worth noting that this bionic strategy considered both molecular structure and assembled form,which enabled this hairy microgel to achieve low friction in aqueous medium.Meanwhile,the effective lubrication was still achieved when using MBs-g-MGs at high temperature,indicating that this microgel maintains a good lubricating effect over a wide range of temperature.In addition,this kind of microgel possessed good biocompatibility,which laid the foundation for potential biomedical applications.Looking beyond,these biomimetic microgels may provide an effective lubricating effect for water-based sliding interfaces,especially in biomedical systems.
基金supported by the National Natural Science Foundation of China(Nos.22275137 and 82202342)Natural Science Foundation of Tianjin Municipal Science and Technology Commission(No.21JCYBJC01810).
文摘The research and application of responsive materials have long been hampered by their complicated designs and tedious construction processes.Besides,many current responsive materials show retard or weak responsiveness.In this study,responsive hybrid poly(vinyl alcohol)hydrogel membranes with embedded poly(N-isopropylacrylamide-acrylic acid)microgels as valves were constructed by simple mixing and subsequent freezing-thawing process.In the structure of the membranes,the matrix poly(vinyl alcohol)chains thread through and entangle with the microgels,and the microgels are firmly constrained within the hybrid hydrogel network.The fast and sharp temperature responsiveness of the embedded microgels was largely retained and endowed the hydrogel membrane with excellent temperature and pH responsiveness.Moreover,the hydrogel membrane showed excellent fatigue resistance in both temperature and pH-responsive flux examination.This study presented the great potential of these hybrid hydrogel membranes in biomedical applications and provided a new strategy for the future design and construction of responsive biomaterials.
基金This work was supported by National Natural Science Foundation of China,Nos.32171353,52073314Guangdong Key Areas Research and Development Program,No.2020B1111150003+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2022A1515011388Science and Technology Projects of Guangzhou,No.202002020078。
文摘The printability of bioink and post-printing cell viability is crucial for extrusion-based bioprinting.A proper bioink not only provides mechanical support for structural fidelity,but also serves as suitable three-dimensional(3D)microenvironment for cell encapsulation and protection.In this study,a hydrogel-based composite bioink was developed consisting of gelatin methacryloyl(GelMA)as the continuous phase and decellularised extracellular matrix microgels(DMs)as the discrete phase.A flow-focusing microfluidic system was employed for the fabrication of cell-laden DMs in a high-throughput manner.After gentle mixing of the DMs and GelMA,both rheological characterisations and 3D printing tests showed that the resulting DM-GelMA hydrogel preserved the shear-thinning nature,mechanical properties,and good printability from GelMA.The integration of DMs not only provided an extracellular matrix-like microenvironment for cell encapsulation,but also considerable shear-resistance for high post-printing cell viability.The DM sizes and inner diameters of the 3D printer needles were correlated and optimised for nozzle-based extrusion.Furthermore,a proof-of-concept bioink composedg of RSC96 Schwann cells encapsulated DMs and human umbilical vein endothelial cell-laden GelMA was successfully bioprinted into 3D constructs,resulting in a modular co-culture system with distinct cells/materials distribution.Overall,the modular DM-GelMA bioink provides a springboard for future precision biofabrication and will serve in numerous biomedical applications such as tissue engineering and drug screening.
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 the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(32201118,52073060,and 52103196)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, immunoadjuvant, and immune checkpoint inhibitor is presented by microfluidic electrospray technology and liquid nitrogen treatment. Owing to the encapsulation of cryo-shocked cancer cells and immunoadjuvant, the microgels can recruit dendritic cells and activate them in situ, and evoke a robust immune response. Moreover, with the combination of the immune checkpoint inhibitor, the antitumor immune response is further enhanced by inhibiting the interaction of PD1 and PDL1. With this, the excellent anti-recurrence and anti-metastasis efficacy of the microgels are demonstrated in an orthotopic breast cancer mouse model. Besides, because of the excellent biocompatibility and appropriate degradation performance, the microgels can provide support for normal cell adhesion and growth, which is beneficial to tissue reconstruction. These properties indicate the great value of the cryo-shocked cancer cell microgels for efficient tumor postoperative combination immunotherapy and tissue regeneration.
基金supported by the National Natural Science Foundation of China(No.51875155)。
文摘The tribological behavior of 316L stainless steel/CoCrMo alloy contacts under aqueous lubrication was investigated in this work.Three types of microgels including poly(N-isopropylacrylamide)(PNIPAM),polyacrylic acid(PAA),and poly(N-isopropylacrylamide-co-acrylic acid)(PNIPAM-co-PAA)were prepared and used as lubricant additives in aqueous solutions.Tribological tests were conducted using a ball-on-disk reciprocating tribometer,over a range of temperatures,pH,and concentrations of the microgels.The PNIPAM-co-PAA microgels were proven to have excellent anti-friction and anti-wear properties,depending on the temperature and pH values of the solutions.The maximum friction coefficient coincided with the lower critical solution temperature of the PNIPAM-co-PAA microgels at 32°C.At the same time,the friction coefficient increased with the increase in pH value of the lubricant solution with the PNIPAM-co-PAA microgels.The unique thermal-and pH-sensitive properties of the PNIPAM-co-PAA microgels provided a new strategy for controlling the friction and wear of steel/CoCrMo alloy contacts under aqueous lubrication.
基金sponsored by the National Natural Science Foundation of China(Grant Nos.51873071,32071321)the National Key Research and Development Program of China(2018YFC1106300).
文摘Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.
基金financially supported by the National Key Research and Development Program of China(2017YFC1103900)the National Natural Science Foundation of China(81871502,81701843,and 81671837)+3 种基金the Shanghai Excellent Technical Leader(18XD1421500)the Program of Shanghai Academic/Technology Research Leader(19XD1431100)the Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01)the Clinical Research Plan of SHDC(No.SHDC2020CR2045B).
文摘Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration.Decalcified bone matrix(DBM)is considered as an ideal bone regeneration scaffold,but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration.To address these problems,we proposed a novel strategy of bone regeneration units(BRUs)based on microgels produced by photo-crosslinkable and microfluidic techniques,containing both the osteogenic ingredient DBM and vascular endothelial growth factor(VEGF)for accurate biomimic of an osteoinductive microenvironment.The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion,proliferation,and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.BRUs were successfully constructed by seeding BMSCs onto microgels,which achieved reliable bone regeneration in vivo.Finally,by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength,a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia.The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.
文摘Diabetes is a serious public health problem affecting 422 million people worldwide. Traditional diabetes management often requires multiple daily insulin injections, associated with pain and inadequate glycemia control. Herein, we have developed an ultrasound-triggered insulin delivery system capable of pulsatile insulin release that can provide both long-term sustained and fast on-demand responses. In this system, insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsules are encapsulated within chitosan microgels. The encapsulated insulin in nanocapsules can passively diffuse from the nanoparticle but remain restricted within the microgel. Upon ultrasound treatment, the stored insulin in microgels can be rapidly released to regulate blood glucose levels. In a chemically-induced type 1 diabetic mouse model, we demonstrated that this system, when activated by 30 s ultrasound administration, could effectively achieve glycemic control for up to one week in a noninvasive, localized, and pulsatile manner.
基金the National Natural Science Foundation of China(No.21704092)Science Foundation of Zhejiang SciTech University(No.16062194-Y)for financial support
文摘Microgels with a thermo-sensitive poly(N-isopropylacrylamide)(polyNIPAm) backbone and bis-imidazolium(VIM) ionic cross-links, denoted as poly(NIPAm-co-VIM), were successfully prepared. The as-synthesized ionic microgels were converted to nanoreactors, denoted as Au@PNI MGs, upon generation and immobilization of gold nanoparticles(Au NPs) of 5–8 nm in size into poly(NIPAm-co-VIM). The content of Au NPs in microgels could be regulated by controlling the 1,6-dibromohexane/vinylimidazole molar ratio in the quaternization reaction. The microgel-based nanoreactors were morphologically spherical and uniform in size, and presented reversible thermo-sensitive behavior with volume phase transition temperatures(VPTTs) at 39–40 °C. The Au@PNI MGs were used for the reduction of 4-nitrophenol, of which the catalytic activity could be modulated by temperature.
基金supported by Key Research and Development Project of Hubei Province[Number 2020BCB022]Opening Fund of State Key Laboratory of Virology of Wuhan University[grant number 2022KF002]+2 种基金Royal Society International Exchanges Scheme[IECNSFC201116]The Academy of Medical Sciences/Wellcome Trust[Springboard grantSBF007100054]。
文摘Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2.Methods In this study,a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein(S protein)in human saliva.The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid,and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication.The electrochemical performance of the sensor was evaluated through differential pulse voltammetry.Results Under optimal experimental conditions,the linear range of the sensor was 10-13-10-9 mg/m L,whereas the detection limit was 9.55 fg/mL.Furthermore,the S protein was instilled in artificial saliva as the infected human saliva model,and the sensing platform showed satisfactory detection capability.Conclusion The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein,indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.
基金supported by the National Natural Science Foundation of China(52004305)the Postdoctoral Research Foundation of China(2021M693497)the Science Foundation of China University of Petroleum,Beijing(2462020XKBH006)。
文摘Injecting CO_(2)into the underground for oil displacement and shortage is an important technique for carbon capture,utilization and storage(CCUS).One of the main problems during the CO_(2)injection is the channeling plugging.Finding an effective method for the gas channeling plugging is a critical issue in the CO_(2)EOR process.In this work,an acid-resistance microgel named dispersed particle gel(DPG)was characterized and its stability was tested in the CO_(2)environment.The microgel size selection strategies for the homogeneous and heterogeneous reservoirs were respectively investigated using the single core flooding and three parallel core flooding experiments.Moreover,the comparison of microgel alternate CO_(2)(MAC)injection and water alternate CO_(2)(WAC)injection in the dual core flooding experiments were presented for the investigation of the role of microgel on the conformance control in CO_(2)flooding process.The results have shown that the microgel featured with ANH and CAN groups can keep its morphology after aging 7 days in the CO_(2)environment.Where,the small microgel with unobstructed migration and large microgel with good plugging efficiency for the high permeability zone were respectively featured with the higher recovery factor in homogeneous and heterogeneous conditions,which indicate they are preferred used for the oil displacement and conformance control.Compared to WAC injection,MAC injection had a higher incremental recovery factor of 12.4%.It suggests the acid-resistance microgel would be a good candidate for the conformance control during CO_(2)flooding process.
文摘While deployment of intracoronary stents has been shown to reduce restenosis, stenting can also damage the endothelial monolayer lining the vessel wall, leading to possible in-stent thrombosis. Local drug delivery from stent surfaces represents a means of delivering therapeutic doses of drug directly to the target site. The aim of this study was to elute fluvastatin, which can inhibit vascular smooth muscle cell proliferation, and xemilofiban, which prevents platelet adhesion and aggregation, together in bioactive concentrations from the same copolymer system. Combined elution from thermoresponsive N-isopropylacrylamide (NiPAAm)/N-tert-butylacrylamide (NtBAAm)-derived copolymer systems was achieved using microgels (NiPAAm/NtBAAm 65/35 wt/wt) randomly dispersed in 85/15 matrices. Fluvastatin elution from 5 mm films over a 14-day period showed initial burst release, which leveled off. Of the total incorporated (8.33 ± 0.21 nmol, n=4), 68.5 % was eluted during this period. Xemilofiban release was measured in terms of its ability to inhibit platelet adhesion, using a microfluidic system. To investigate the influence of location and hydrophobicity on elution of bioactivity, three separate systems were employed. While elution of anti-adhesive activity from the system containing xemilofiban-loaded matrices was more dramatic in the short term, a more sustained level of inhibition was achieved when xemilofiban had been incorporated into microgels. All samples investigated for anti-adhesive activity also decreased human coronary artery smooth muscle cell proliferation. Therefore xemilofiban has potential as an agent for preventing in-stent thrombosis. Our study has demonstrated the feasibility of using this novel matrix/microgel system to regulate simultaneous release of both agents in bioactive concentrations.
基金sponsored by the National Nature Science Foundation of China(Nos.U1609207,81827804).
文摘Three-dimensional(3D)bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological functions.However,the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated cells.Herein,a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks(MPNs)for enhancing nutrient delivery and cell growth.The sacrificial microgel-laden bioink,which contains cell/gelatin methacryloyl(GelMA)mixture and gelled gelatin microgel,is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold platform.Then,the construct is permanently stabilized through photo-crosslinking of GelMA.The MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin microgel.These MPNs allowed for effective oxygen/nutrient diffusion,facilitating the generation of bioactive tissues.Specifically,osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs(≥1 cm)with MPNs showed enhanced bioactivity during culture.The 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.