Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utiliz...Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utilization,environmental friendliness,porosity,amphiphilicity,and strong adhesive properties.In addition,they display excellent biocompatibility and biodegradability,which significantly enhances the stability and targeting of drugs within the body.Spores and pollen can be extracted using methods such as acidic solutions,alkaline solutions,or enzyme treatments to obtain sporopollenin,which is an extremely resilient and chemically inert complex biopolymer.The sporopollenin extracted through this process removes the original bioactive substances,such as cell nuclei,enzymes,and DNA,providing greater drug loading capacity and containing no potential allergens or immunogens,thus further enhancing its drug loading capacity and improving safety in therapeutic applications.Due to these beneficial attributes,spores,pollen and sporopollenin have gained widespread use in a variety of drug delivery systems,such as targeted delivery,sustained drug delivery,toxicity mitigation,flavor masking,vaccine delivery,delivery of labile substances,and other applications.This review introduces the types of natural spores and pollen commonly used in drug delivery systems,including their main components,common effects,and uses in drug delivery systems,and so on.It subsequently summarizes novel optimization methods in their processing,such as physical treatment,surface modification,and chemical modification,which enable higher drug loading efficiency,stability,and targeting,among other benefits.Additionally,this paper reviews the research progress and applications of natural spores,pollen,and sporopollenin in drug delivery systems,while also touching on some innovative research content,such as novel nanomotor microcarriers developed based on pollen.Based on these research findings,we further elaborate on the advantages of spores,pollen,and sporopollenin in drug delivery systems.For example,they have high stability and drug loading capacity,good adhesion,excellent targeting,and are easy to modify functionally.Currently,they show promising prospects in the fields of targeted drug delivery,sustained-release drug delivery,as well as the delivery of drugs that are effective but slightly toxic,and are often used in research on the treatment of diseases such as cancer and inflammation.We have also highlighted the challenges they face in various applications and identified some issues that need to be addressed,including difficulties in largescale production,the need to improve extraction and purification processes,and the existence of a low but still noteworthy risk of allergies,in order to fully leverage their potential in drug delivery applications.According to current research,although spores,pollen,and sporopollenin face some unresolved issues in clinical drug delivery,they still have great potential overall and are expected to become a new generation of green drug delivery platforms.In the future,further research into their unique physical and chemical properties and structural characteristics will help develop more efficient and stable drug delivery systems to meet diverse treatment needs.We believe that continued exploration of natural spores,pollen,and sporopollenin will drive this emerging field to achieve continuous breakthroughs and progress,ultimately making an important contribution to the cause of human health.展开更多
The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers f...The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers for cell culture,trypsinization is often necessary during cell collection,leading to partial cells damage.In this work,we developed a thermoresponsive glass microcarrier modified with poly(γ-propargyl-L-glutamate)(PPLG)and poly(N-isopropylacrylamide)(PNIPAM).We utilized these microcarriers for three-dimensional cell culture and enzyme-free cell harvesting,and the results indicated that the prepared microcarriers exhibited excellent non-invasive cell culture performance.展开更多
AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion...AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.展开更多
Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-resp...Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.展开更多
objective: To cultivate human liver cell line (CL-1) on microcarriers and study the synthetic and transformational function of this culture system. Methods:CL-1 were cultivated on Cytodex-3 microcarriers. The cell gro...objective: To cultivate human liver cell line (CL-1) on microcarriers and study the synthetic and transformational function of this culture system. Methods:CL-1 were cultivated on Cytodex-3 microcarriers. The cell growth was kinetically inspected with light microscope and scanning electronic microscope on the lst, 3rd, 5th, 7th, 9th day, and the amount of diazepam transformation and albumin synthesis were deter mined at the same time. Results:On 7th day after inoculating, the CL-1 cell density could reach 2. 16 ×106/ ml ; the amount of diazepam trans formation was 619 μg and albumin synthesis 78. 23 μg. Conclusion:CL-1 can be cultivated to a high density on microcarriers and has hepatic specific biotransformation and biosynthesis functions. So the culture system may be further studied for being used as the biomaterial of bioartificial liver.展开更多
The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction condition...The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction conditions were optimized. Morphology of rat hepatocytes cultured on CMs was observed using phase contrast microscope and scanning electron microscope, and the metabolic activities were measured. Rat hepatocytes cultured on CMs retained the spherical shape as they have in vivo and had high metabolic activities. Fructose can enhance the metabolic activity of hepatocytes and the modified CMs are promising scaffold for hepatocytes attachment.展开更多
Using polyvinyl alcohol (PVA) as raw material and vacuum pump oil as oil phase medium, PVA-based microcarriers were prepared by suspension method. The diameters of the beads were 100-180μm. LO2 cells were cultured on...Using polyvinyl alcohol (PVA) as raw material and vacuum pump oil as oil phase medium, PVA-based microcarriers were prepared by suspension method. The diameters of the beads were 100-180μm. LO2 cells were cultured on PVA-based microcarriers and cytodexIII microcarriers. Morphology, attachment and growth rate of LO2 cells were studied.展开更多
BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative method for treating liver failure. The core of the BAL system is culturing liver cells in vitro with high density and activity. Microcarri...BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative method for treating liver failure. The core of the BAL system is culturing liver cells in vitro with high density and activity. Microcarrier culture is a mode of high-density culture. We set out to prepare a novel porous microcarrier to improve the activity of liver cells in vitro. METHODS: Chitosan was used to prepare a novel porous spherical microcarrier with interconnected structure. The chitosan porous microcarriers (CPMs) were modified with gelatin to improve their biocompatibility. CPMs were co-cultured with liver cells, HL-7702 (L-02), to evaluate their effect on cell culture. RESULTS: The average size of the CPMs was about 400 μm in diameter and their apertures were less than 30 μm. The pores of the microcarrier were interconnected. After fixation by sodium tripolyphosphate, the structure of the first freeze-dried CPMs was stable. To further improve the biocompatibility, the surface of CPMs was modified with gelatin through chemical crosslinking (GM-CPMs). Comparing the proliferation curves of L-02 cells cultured on simple CPMs, GM-CPMs and tissue culture polystyrene (TCPS, a mode of planar cell culture), the proliferation rates were similar in the first 5 days and the cells proliferated until day 8 in culture with microcarriers. The OD value of liver cells cultured on GM-CPMs was 1.97-fold higher than that on TCPS culture at day 8. Levels of urea and albumin in supernatants of cells cultured on GM-CPMs increased steadily for 8 days, and were clearly higher than those of cells cultured on TCPS (P<0.05).CONCLUSIONS: The novel CPMs were promising microcarriers for hepatocyte culture and the GM-CPM seemed better. Porous microcarrier culture was beneficial for hepatocyte function and activity.展开更多
Long-term exposure to ultraviolet radiation compromises skin structural integrity and results in disruption of normal physiological functions.Stem cells have gained attention in anti-photoaging,while controlling the t...Long-term exposure to ultraviolet radiation compromises skin structural integrity and results in disruption of normal physiological functions.Stem cells have gained attention in anti-photoaging,while controlling the tissue mechanical microenvironment of cell delivery sites is crucial for regulating cell fate and achieving optimal therapeutic performances.Here,we introduce a mechanically regulated human recombinant collagen(RHC)microcarrier generated through microfluidics,which is capable of modulating stem cell differentiation to treat photoaged skin.By controlling the cross-linking parameters,the mechanical properties of microcarriers could precisely tuned to optimize the stem cell differentiation.The microcarriers are surface functionalized with fibronectin(Fn)-platelet derived growth factor-BB(PDGF-BB)to facilitate adipose derived mesenchymal stem cells(Ad-MSCs)loading.In in vivo experiments,subcutaneous injection of stem cell loaded RHC microcarriers significantly reduced skin wrinkles after ultraviolet-injury,effectively promoted collagen synthesis,and increased vascular density.These encouraging results indicate that the present mechanically regulated microcarriers have great potential to deliver stem cells and regulate their differentiation for anti-photoaging treatments.展开更多
Cartilage tissues possess an extremely limited capacity for self-repair,and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significantadvances...Cartilage tissues possess an extremely limited capacity for self-repair,and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significantadvances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains achallenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stemcells (BMSCs) within porous gelatin microcarriers (GMs) and induceddifferentiation. These microtissues were then injected for thepurpose of treating cartilage defects in vivo, via a minimally invasiveapproach. GMs were found to be noncytotoxic and favorable for cellattachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells andabundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28days. Notably,ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenicdifferentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achievedsuperior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilagemicrotissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk ofsecondary damage associated with traditional surgical techniques.展开更多
Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells,drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help recons...Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells,drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct agood microenvironment for tissue repair. In order to achieve more ideal performance and face more complextissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond toexternal stimuli. These microcarriers have the functions of directional movement, targeted enrichment, materialrelease control, and providing signals conducive to tissue repair. Given the high controllability and designabilityof magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in thisreview. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed.In summary, through the design with clinical translation ability, meaningful and comprehensiveexperimental characterization, and in-depth study and application of tissue repair mechanisms, stimuliresponsivemicrocarriers have great potential in tissue repair.展开更多
Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wid...Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wide range of medical fields, especially the cartilage tissue engineering (TE). Notably, microcarrier systems provide an attractive method for regulating cell phenotype and microtissue maturations, they also serve as powerful injectable carriers and are combined with new technologies for cartilage regeneration. In this review, we introduced the typical methods to fabricate various types of microcarriers and discussed the appropriate ma-terials for microcarriers. Furthermore, we highlighted recent progress of applications and general design prin-ciple for microcarriers. Finally, we summarized the current challenges and promising prospects of microcarrier-based systems for medical applications. Overall, this review provides comprehensive and systematic guidelines for the rational design and applications of microcarriers in cartilage TE.展开更多
Due to a worldwide focus on sustainable materials for human health and economy services, more and more natural renewable biomass are regarded as promising materials that could replace synthetic polymers and reduce glo...Due to a worldwide focus on sustainable materials for human health and economy services, more and more natural renewable biomass are regarded as promising materials that could replace synthetic polymers and reduce global dependence on petroleum resources. Cellulose is known as the most abundant renewable polymer in nature, varieties of cellulose-based products have been developed and have gained growing interest in recent years. In this review, a kind of water-soluble cellulose derivative, i.e., sodium cellulose sulfate (NaCS) is introduced. Details about NaCS's physicochemical properties like solubility, biocompatibility, biodegradability, degree of substitution, etc. are systematically elaborated. And promising applications of NaCS used as biomaterials for microcarriers' designing, such as microcell- carriers, micro-drug-carriers, etc., are presented.展开更多
Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are effici...Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are efficient 3D cell culture scaffolds,which can also prevent cell anoikis by providing substrate for adhesion during transplantation.Here,we demonstrate for the first time microcarrier-based cell transplantation in peripheral nerve repair.We first prepared macroporous chitosan microcarriers(CSMCs)by the emulsion-phase separation method,and then decorated the CSMCs with polylysine(pl-CSMCs)to improve cell affinity.We then loaded the pl-CSMCs with adipose-derived stem cells(ADSCs)and injected them into electrospun polycaprolactone/chitosan NGCs to repair rat sciatic nerve defects.The ADSCs-laden pl-CSMCs effectively improved nerve regeneration as demonstrated by evaluation of histology,motor function recovery,electrophysiology,and gastrocnemius recovery.With efficient cell transplantation,convenient operation,and the multiple merits of ADSCs,the ADSCs-laden pl-CSMCs hold good potential in peripheral nerve repair.展开更多
Reusable microcarriers with appropriate surface topography,mechanical properties,as well as biological modification through decellularization facilitating repeated cell culture are crucial for tissue engineering appli...Reusable microcarriers with appropriate surface topography,mechanical properties,as well as biological modification through decellularization facilitating repeated cell culture are crucial for tissue engineering applications.Herein,we report the preparation of topological polyetheretherketone(PEEK)microcarriers via gas-driven and solvent exchange method followed by hydrothermal treatment at high temperature and pressure.After hydrothermal treated for 8 h,the resulting topological PEEK microcarriers exhibit walnut-like surface topography and good sphericity as well as uniform size distribution of 350.24619.44 mm.And the average width between ravine-patterned surface of PEEK microcarriers is 7806290 nm.After repeated steam sterilization by autoclaving for three times,topological PEEK microcarriers show nearly identical results compared with previous ones indicating strong tolerance to high temperature and pressure.This is a unique advantage for large-scale cell expansion and clinical applications.Moreover,PEEK microcarriers with special topography possess higher protein adsorption efficiency.In addition,the reutilization and biofunctionalization with repeated decellularization of topological PEEK microcarriers show highly beneficial for cell adhesion and proliferation.Therefore,our study is of great importance for new generation microcarriers with micro-and nano-scale surface feature for a broad application prospect in tissue engineering.展开更多
Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer,supporting cell attachment and growth with sufficient cell seeding density.In this study,porous polyethereth...Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer,supporting cell attachment and growth with sufficient cell seeding density.In this study,porous polyetheretherketone(PEEK)microcarriers coated with mineralized extracellular matrix(mECM),known for their chemical,mechanical and biological superiority,were developed for orthopedic applications.Porous PEEK microcarriers were derived from smooth microcarriers using a simple wet-chemistry strategy involving the reduction of carbonyl groups.This treatment simultaneously modified surface topology and chemical composition.Furthermore,the microstructure,protein absorption,cytotoxicity and bioactivity of the obtained porous microcarriers were investigated.The deposition of mECM through repeated recellularization and decellularization on the surface of porous MCs further promoted cell proliferation and osteogenic activity.Additionally,the mECM coated porous microcarriers exhibited excellent bone regeneration in a rat calvarial defect repair model in vivo,suggesting huge potential applications in bone tissue engineering.展开更多
Microcarriers have a demonstrated value for biomedical applications,in particular for drug delivery and three-dimensional cell culture.Attempts to develop this technique tend to focus on the fabrication of functional ...Microcarriers have a demonstrated value for biomedical applications,in particular for drug delivery and three-dimensional cell culture.Attempts to develop this technique tend to focus on the fabrication of functional microparticles by using convenient methods with innovative but accessible materials.Inspired by the process of boiling eggs in everyday life,which causes the solidification of egg proteins,we present a new microfluidic‘‘cooking"approach for the generation of egg-derived microcarriers for cell culture and drug delivery.As the egg emulsion droplets are formed with exquisite precision during the microfluidic emulsification,the resultant egg microcarriers present highly monodisperse and uniform morphologies at the size range of hundred microns to one millimeter.Benefiting from the excellent biocompatibility of the egg protein components,the obtained microcarriers showed good performances of cell adherence and growth.In addition,after a freezing treatment,the egg microcarriers were shown to have interconnected porous structures throughout their whole sphere,could absorb and load different kinds of drugs or other active molecules,and work as microcarrier-based delivery systems.These features point to the potential value of the microfluidic egg microcarriers in biomedicine.展开更多
Mechanical force is crucial in the whole process of embryonic development.However,the role of trophoblast mechanics during embryo implantation has rarely been studied.In this study,we constructed a model to explore th...Mechanical force is crucial in the whole process of embryonic development.However,the role of trophoblast mechanics during embryo implantation has rarely been studied.In this study,we constructed a model to explore the effect of stiffness changes in mouse trophoblast stem cells(mTSCs)on implantation:microcarrier was prepared by sodium alginate using a droplet microfluidics system,and mTSCs were attached to the microcarrier surface with laminin modifications,called T(micro).Compared with the spheroid,formed by the self-assembly of mTSCs(T(sph)),we could regulate the stiffness of the microcarrier,making the Young’s modulus of mTSCs(367.70±79.81 Pa)similar to that of the blastocyst trophoblast ectoderm(432.49±151.90 Pa).Moreover,T(micro)contributes to improve the adhesion rate,expansion area and invasion depth of mTSCs.Further,T(micro)was highly expressed in tissue migration-related genes due to the activation of the Rho-associated coiled-coil containing protein kinase(ROCK)pathway at relatively similar modulus of trophoblast.Overall,our study explores the embryo implantation process with a new perspective,and provides theoretical support for understanding the effect of mechanics on embryo implantation.展开更多
Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and...Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation,passaging,harvesting and downstream application is limited.Therefore,we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers(GMs)for mesenchymal stromal cells(MSCs)expansion and tissue engineering.Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment,expansion and harvest,and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency.Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase,respectively.Furthermore,we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds.These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture,expansion and tissue engineering.展开更多
Microcarriers containing cellulose-derived materials have been successfully applied to enhance the growth of anchorage-dependent cells maintained especially in bioreactors.By replacing microcarriers with nanocarriers ...Microcarriers containing cellulose-derived materials have been successfully applied to enhance the growth of anchorage-dependent cells maintained especially in bioreactors.By replacing microcarriers with nanocarriers containing dextran,we hypothesized that the density of the anchorage-dependent cells would rise dramatically because the decreased particle size and associated enhancement in surface to volume ratios of nanoparticles contained within the nanoemulsion-based nanocarriers would increase the number of dextran molecules for the anchorage-dependent cells to attach to.Our studies utilized self-assembly nanoemulsions(SANE)formed by a modified phase inversion temperature(PIT)process to produce dextran oil and surfactant-containing nanocarriers having mean particle sizes of 26 nm compared to microcarriers which were greater than 6000 nm.Our results demonstrated that dextran-containing nanocarriers allowed up to 10 fold greater cell density,12% more media lactate concentration,83%higher cell lysate protein and 59% greater glucose concentration,used as a measure of polymer levels in the nanocarriers compared to microcarriers.In conclusion,nanocarriers with increased numbers of dextran molecules,developed in these studies may be useful to further increase the production of anchorage-dependent animal cell-derived products or production of mass cell growth for other applications.展开更多
基金supported by a grant from The National Natural Science Foundation of China(32000997)。
文摘Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utilization,environmental friendliness,porosity,amphiphilicity,and strong adhesive properties.In addition,they display excellent biocompatibility and biodegradability,which significantly enhances the stability and targeting of drugs within the body.Spores and pollen can be extracted using methods such as acidic solutions,alkaline solutions,or enzyme treatments to obtain sporopollenin,which is an extremely resilient and chemically inert complex biopolymer.The sporopollenin extracted through this process removes the original bioactive substances,such as cell nuclei,enzymes,and DNA,providing greater drug loading capacity and containing no potential allergens or immunogens,thus further enhancing its drug loading capacity and improving safety in therapeutic applications.Due to these beneficial attributes,spores,pollen and sporopollenin have gained widespread use in a variety of drug delivery systems,such as targeted delivery,sustained drug delivery,toxicity mitigation,flavor masking,vaccine delivery,delivery of labile substances,and other applications.This review introduces the types of natural spores and pollen commonly used in drug delivery systems,including their main components,common effects,and uses in drug delivery systems,and so on.It subsequently summarizes novel optimization methods in their processing,such as physical treatment,surface modification,and chemical modification,which enable higher drug loading efficiency,stability,and targeting,among other benefits.Additionally,this paper reviews the research progress and applications of natural spores,pollen,and sporopollenin in drug delivery systems,while also touching on some innovative research content,such as novel nanomotor microcarriers developed based on pollen.Based on these research findings,we further elaborate on the advantages of spores,pollen,and sporopollenin in drug delivery systems.For example,they have high stability and drug loading capacity,good adhesion,excellent targeting,and are easy to modify functionally.Currently,they show promising prospects in the fields of targeted drug delivery,sustained-release drug delivery,as well as the delivery of drugs that are effective but slightly toxic,and are often used in research on the treatment of diseases such as cancer and inflammation.We have also highlighted the challenges they face in various applications and identified some issues that need to be addressed,including difficulties in largescale production,the need to improve extraction and purification processes,and the existence of a low but still noteworthy risk of allergies,in order to fully leverage their potential in drug delivery applications.According to current research,although spores,pollen,and sporopollenin face some unresolved issues in clinical drug delivery,they still have great potential overall and are expected to become a new generation of green drug delivery platforms.In the future,further research into their unique physical and chemical properties and structural characteristics will help develop more efficient and stable drug delivery systems to meet diverse treatment needs.We believe that continued exploration of natural spores,pollen,and sporopollenin will drive this emerging field to achieve continuous breakthroughs and progress,ultimately making an important contribution to the cause of human health.
基金supported by the name of National Key Research and Development Program of China(No.2021YFB3800900)the National Natural Science Foundation of China(Nos.51925305,51873208,1833010,51973217,52373161)Jilin Province Science and Technology Development Program(No.20200201075JC)。
文摘The development of large-scale cell cultivation and non-invasive cell harvesting is highly desired in various fields,including biological regeneration and pharmaceutical research.When using traditional microcarriers for cell culture,trypsinization is often necessary during cell collection,leading to partial cells damage.In this work,we developed a thermoresponsive glass microcarrier modified with poly(γ-propargyl-L-glutamate)(PPLG)and poly(N-isopropylacrylamide)(PNIPAM).We utilized these microcarriers for three-dimensional cell culture and enzyme-free cell harvesting,and the results indicated that the prepared microcarriers exhibited excellent non-invasive cell culture performance.
基金the National Natural Science Foundation of China,No.39570212
文摘AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.
文摘Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.
文摘objective: To cultivate human liver cell line (CL-1) on microcarriers and study the synthetic and transformational function of this culture system. Methods:CL-1 were cultivated on Cytodex-3 microcarriers. The cell growth was kinetically inspected with light microscope and scanning electronic microscope on the lst, 3rd, 5th, 7th, 9th day, and the amount of diazepam transformation and albumin synthesis were deter mined at the same time. Results:On 7th day after inoculating, the CL-1 cell density could reach 2. 16 ×106/ ml ; the amount of diazepam trans formation was 619 μg and albumin synthesis 78. 23 μg. Conclusion:CL-1 can be cultivated to a high density on microcarriers and has hepatic specific biotransformation and biosynthesis functions. So the culture system may be further studied for being used as the biomaterial of bioartificial liver.
基金The Natural Science Foundation of China (No. 30070222)
文摘The fructose modified chitosan microcarries (CMs) were prepared by the reaction of glutaraldehyde with fructose-modified chitosan. Various factors that influence the preparation were studied and the reaction conditions were optimized. Morphology of rat hepatocytes cultured on CMs was observed using phase contrast microscope and scanning electron microscope, and the metabolic activities were measured. Rat hepatocytes cultured on CMs retained the spherical shape as they have in vivo and had high metabolic activities. Fructose can enhance the metabolic activity of hepatocytes and the modified CMs are promising scaffold for hepatocytes attachment.
基金The National Natural Science Foundation of China(No.29776027).
文摘Using polyvinyl alcohol (PVA) as raw material and vacuum pump oil as oil phase medium, PVA-based microcarriers were prepared by suspension method. The diameters of the beads were 100-180μm. LO2 cells were cultured on PVA-based microcarriers and cytodexIII microcarriers. Morphology, attachment and growth rate of LO2 cells were studied.
基金supported by grants from the National Natural Science Foundation of China (30672043, 30772105)the National 863 program of China (2008AA02Z417)
文摘BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative method for treating liver failure. The core of the BAL system is culturing liver cells in vitro with high density and activity. Microcarrier culture is a mode of high-density culture. We set out to prepare a novel porous microcarrier to improve the activity of liver cells in vitro. METHODS: Chitosan was used to prepare a novel porous spherical microcarrier with interconnected structure. The chitosan porous microcarriers (CPMs) were modified with gelatin to improve their biocompatibility. CPMs were co-cultured with liver cells, HL-7702 (L-02), to evaluate their effect on cell culture. RESULTS: The average size of the CPMs was about 400 μm in diameter and their apertures were less than 30 μm. The pores of the microcarrier were interconnected. After fixation by sodium tripolyphosphate, the structure of the first freeze-dried CPMs was stable. To further improve the biocompatibility, the surface of CPMs was modified with gelatin through chemical crosslinking (GM-CPMs). Comparing the proliferation curves of L-02 cells cultured on simple CPMs, GM-CPMs and tissue culture polystyrene (TCPS, a mode of planar cell culture), the proliferation rates were similar in the first 5 days and the cells proliferated until day 8 in culture with microcarriers. The OD value of liver cells cultured on GM-CPMs was 1.97-fold higher than that on TCPS culture at day 8. Levels of urea and albumin in supernatants of cells cultured on GM-CPMs increased steadily for 8 days, and were clearly higher than those of cells cultured on TCPS (P<0.05).CONCLUSIONS: The novel CPMs were promising microcarriers for hepatocyte culture and the GM-CPM seemed better. Porous microcarrier culture was beneficial for hepatocyte function and activity.
基金supported by the National Key Research and Development Program of China(2022YFA1105300)the National Natural Science Foundation of China(52073060,61927805 and 82400718)+5 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)supported by the Research Project(347897)Solution for Health Profile(336355)InFLAMES Flagship(337531)"Printed Intelligence Infrastructure"(PII-FIRI)"from Research Council of Finland.
文摘Long-term exposure to ultraviolet radiation compromises skin structural integrity and results in disruption of normal physiological functions.Stem cells have gained attention in anti-photoaging,while controlling the tissue mechanical microenvironment of cell delivery sites is crucial for regulating cell fate and achieving optimal therapeutic performances.Here,we introduce a mechanically regulated human recombinant collagen(RHC)microcarrier generated through microfluidics,which is capable of modulating stem cell differentiation to treat photoaged skin.By controlling the cross-linking parameters,the mechanical properties of microcarriers could precisely tuned to optimize the stem cell differentiation.The microcarriers are surface functionalized with fibronectin(Fn)-platelet derived growth factor-BB(PDGF-BB)to facilitate adipose derived mesenchymal stem cells(Ad-MSCs)loading.In in vivo experiments,subcutaneous injection of stem cell loaded RHC microcarriers significantly reduced skin wrinkles after ultraviolet-injury,effectively promoted collagen synthesis,and increased vascular density.These encouraging results indicate that the present mechanically regulated microcarriers have great potential to deliver stem cells and regulate their differentiation for anti-photoaging treatments.
基金supported by the National Natural Science Foundation of China(52173151,82002734,51803067)the Natural Science Foundation of Guangdong Province of China(2021A1515011084,2019A1515110312)+1 种基金the Fundamental Research Funds for the Central Universities(22qntd1302)the Shenzhen Outbound Postdoctoral Scientific Research Fund(SZBH202108).
文摘Cartilage tissues possess an extremely limited capacity for self-repair,and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significantadvances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains achallenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stemcells (BMSCs) within porous gelatin microcarriers (GMs) and induceddifferentiation. These microtissues were then injected for thepurpose of treating cartilage defects in vivo, via a minimally invasiveapproach. GMs were found to be noncytotoxic and favorable for cellattachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells andabundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28days. Notably,ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenicdifferentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achievedsuperior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilagemicrotissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk ofsecondary damage associated with traditional surgical techniques.
基金supported by National Natural Science Foundation of China(Grant No.52273119,51973018)Key Research and Development Projects of People’s Liberation Army(BWS17J036)Beijing Science and Technology Project(Z191100002019017).
文摘Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells,drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct agood microenvironment for tissue repair. In order to achieve more ideal performance and face more complextissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond toexternal stimuli. These microcarriers have the functions of directional movement, targeted enrichment, materialrelease control, and providing signals conducive to tissue repair. Given the high controllability and designabilityof magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in thisreview. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed.In summary, through the design with clinical translation ability, meaningful and comprehensiveexperimental characterization, and in-depth study and application of tissue repair mechanisms, stimuliresponsivemicrocarriers have great potential in tissue repair.
基金The authors thank Shuo Wang and Shen Ji for helpful discussion.This work was supported by the National Natural Science Foundation of China(Grant No.81773091)the Natural Science Foundation of Beijing Municipality(Grant No.7212020)+4 种基金Science and Technology Planning Project of Beijing Municipal Education Commission(Grant No.KM202110025013)the Beijing Municipal Excellent Talents Project(Grant No.2020A43)Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA16020802)CAS Engineering Laboratory for Intelligent Organ Manufacturing(Grant No.KFJ-PTXM-039)the National Natural Science Foundation of China(Grant No.82001848).
文摘Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wide range of medical fields, especially the cartilage tissue engineering (TE). Notably, microcarrier systems provide an attractive method for regulating cell phenotype and microtissue maturations, they also serve as powerful injectable carriers and are combined with new technologies for cartilage regeneration. In this review, we introduced the typical methods to fabricate various types of microcarriers and discussed the appropriate ma-terials for microcarriers. Furthermore, we highlighted recent progress of applications and general design prin-ciple for microcarriers. Finally, we summarized the current challenges and promising prospects of microcarrier-based systems for medical applications. Overall, this review provides comprehensive and systematic guidelines for the rational design and applications of microcarriers in cartilage TE.
基金China Postdoctoral Science Foundation (No. 2017M611998)the National Natural Science Foundation of China (Grant Nos. 21606002 and 21576233)+2 种基金the Natural Science Foundation of Anhui Province (CN)(No. 1708085QC64)the Doctoral Research Start-up Fund of Anhui University (J01001319)the Undergraduate Research Training Programs for Innovation (Nos. KYXL2017036, 201710357034 and 201710357268).
文摘Due to a worldwide focus on sustainable materials for human health and economy services, more and more natural renewable biomass are regarded as promising materials that could replace synthetic polymers and reduce global dependence on petroleum resources. Cellulose is known as the most abundant renewable polymer in nature, varieties of cellulose-based products have been developed and have gained growing interest in recent years. In this review, a kind of water-soluble cellulose derivative, i.e., sodium cellulose sulfate (NaCS) is introduced. Details about NaCS's physicochemical properties like solubility, biocompatibility, biodegradability, degree of substitution, etc. are systematically elaborated. And promising applications of NaCS used as biomaterials for microcarriers' designing, such as microcell- carriers, micro-drug-carriers, etc., are presented.
基金National Natural Science Foundation of China(Grant No.51773018,51973018)Key Research and Development Projects of People’s Liberation Army(BWS17J036).
文摘Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are efficient 3D cell culture scaffolds,which can also prevent cell anoikis by providing substrate for adhesion during transplantation.Here,we demonstrate for the first time microcarrier-based cell transplantation in peripheral nerve repair.We first prepared macroporous chitosan microcarriers(CSMCs)by the emulsion-phase separation method,and then decorated the CSMCs with polylysine(pl-CSMCs)to improve cell affinity.We then loaded the pl-CSMCs with adipose-derived stem cells(ADSCs)and injected them into electrospun polycaprolactone/chitosan NGCs to repair rat sciatic nerve defects.The ADSCs-laden pl-CSMCs effectively improved nerve regeneration as demonstrated by evaluation of histology,motor function recovery,electrophysiology,and gastrocnemius recovery.With efficient cell transplantation,convenient operation,and the multiple merits of ADSCs,the ADSCs-laden pl-CSMCs hold good potential in peripheral nerve repair.
基金This research was financially supported by the National Natural Science Foundation of China(Projects.51473164 and 51673186)the joint funded program of Chinese Academy of Sciences and Japan Society for the Promotion of Science(GJHZ1519)the Special Fund for Industrialization of Science and Technology Cooperation between Jilin Province and Chinese Academy of Sciences(2017SYHZ0021).
文摘Reusable microcarriers with appropriate surface topography,mechanical properties,as well as biological modification through decellularization facilitating repeated cell culture are crucial for tissue engineering applications.Herein,we report the preparation of topological polyetheretherketone(PEEK)microcarriers via gas-driven and solvent exchange method followed by hydrothermal treatment at high temperature and pressure.After hydrothermal treated for 8 h,the resulting topological PEEK microcarriers exhibit walnut-like surface topography and good sphericity as well as uniform size distribution of 350.24619.44 mm.And the average width between ravine-patterned surface of PEEK microcarriers is 7806290 nm.After repeated steam sterilization by autoclaving for three times,topological PEEK microcarriers show nearly identical results compared with previous ones indicating strong tolerance to high temperature and pressure.This is a unique advantage for large-scale cell expansion and clinical applications.Moreover,PEEK microcarriers with special topography possess higher protein adsorption efficiency.In addition,the reutilization and biofunctionalization with repeated decellularization of topological PEEK microcarriers show highly beneficial for cell adhesion and proliferation.Therefore,our study is of great importance for new generation microcarriers with micro-and nano-scale surface feature for a broad application prospect in tissue engineering.
文摘Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer,supporting cell attachment and growth with sufficient cell seeding density.In this study,porous polyetheretherketone(PEEK)microcarriers coated with mineralized extracellular matrix(mECM),known for their chemical,mechanical and biological superiority,were developed for orthopedic applications.Porous PEEK microcarriers were derived from smooth microcarriers using a simple wet-chemistry strategy involving the reduction of carbonyl groups.This treatment simultaneously modified surface topology and chemical composition.Furthermore,the microstructure,protein absorption,cytotoxicity and bioactivity of the obtained porous microcarriers were investigated.The deposition of mECM through repeated recellularization and decellularization on the surface of porous MCs further promoted cell proliferation and osteogenic activity.Additionally,the mECM coated porous microcarriers exhibited excellent bone regeneration in a rat calvarial defect repair model in vivo,suggesting huge potential applications in bone tissue engineering.
基金supported by the National Natural Science Foundation of China (21473029, 51522302)the NSAF Foundation of China (U1530260)+2 种基金the Natural Science Foundation of Jiangsu Province (BK20140028)the Program for New Century Excellent Talents in Universitythe Scientific Research Foundation of Southeast University
文摘Microcarriers have a demonstrated value for biomedical applications,in particular for drug delivery and three-dimensional cell culture.Attempts to develop this technique tend to focus on the fabrication of functional microparticles by using convenient methods with innovative but accessible materials.Inspired by the process of boiling eggs in everyday life,which causes the solidification of egg proteins,we present a new microfluidic‘‘cooking"approach for the generation of egg-derived microcarriers for cell culture and drug delivery.As the egg emulsion droplets are formed with exquisite precision during the microfluidic emulsification,the resultant egg microcarriers present highly monodisperse and uniform morphologies at the size range of hundred microns to one millimeter.Benefiting from the excellent biocompatibility of the egg protein components,the obtained microcarriers showed good performances of cell adherence and growth.In addition,after a freezing treatment,the egg microcarriers were shown to have interconnected porous structures throughout their whole sphere,could absorb and load different kinds of drugs or other active molecules,and work as microcarrier-based delivery systems.These features point to the potential value of the microfluidic egg microcarriers in biomedicine.
基金supported by National Natural Science Foundation of China(T2222029 and U21A20396)Strategic Priority Research Program of Chinese Academy of Sciences(XDA16020802)+1 种基金CAS Project for Young Scientists in Basic Research(YSBR-012)CAS Engineering Laboratory for Intelligent Organ Manufacturing(KFJ-PTXM-039).
文摘Mechanical force is crucial in the whole process of embryonic development.However,the role of trophoblast mechanics during embryo implantation has rarely been studied.In this study,we constructed a model to explore the effect of stiffness changes in mouse trophoblast stem cells(mTSCs)on implantation:microcarrier was prepared by sodium alginate using a droplet microfluidics system,and mTSCs were attached to the microcarrier surface with laminin modifications,called T(micro).Compared with the spheroid,formed by the self-assembly of mTSCs(T(sph)),we could regulate the stiffness of the microcarrier,making the Young’s modulus of mTSCs(367.70±79.81 Pa)similar to that of the blastocyst trophoblast ectoderm(432.49±151.90 Pa).Moreover,T(micro)contributes to improve the adhesion rate,expansion area and invasion depth of mTSCs.Further,T(micro)was highly expressed in tissue migration-related genes due to the activation of the Rho-associated coiled-coil containing protein kinase(ROCK)pathway at relatively similar modulus of trophoblast.Overall,our study explores the embryo implantation process with a new perspective,and provides theoretical support for understanding the effect of mechanics on embryo implantation.
基金supported by the National Natural Science Foundation of China(Grant No.52075285)the Applied Basic Research Project of Sichuan Province(Grant No.2021YJ0563).
文摘Biopolymer microbeads present substantial benefits for cell expansion,tissue engineering,and drug release applications.However,a fabrication system capable of producing homogeneous microspheres with high precision and controllability for cell proliferation,passaging,harvesting and downstream application is limited.Therefore,we developed a co-flow microfluidics-based system for the generation of uniform and size-controllable gelatin-based microcarriers(GMs)for mesenchymal stromal cells(MSCs)expansion and tissue engineering.Our evaluation of GMs revealed superior homogeneity and efficiency of cellular attachment,expansion and harvest,and MSCs expanded on GMs exhibited high viability while retaining differentiation multipotency.Optimization of passaging and harvesting protocols was achieved through the addition of blank GMs and treatment with collagenase,respectively.Furthermore,we demonstrated that MSC-loaded GMs were printable and could serve as building blocks for tissue regeneration scaffolds.These results suggested that our platform held promise for the fabrication of uniform GMs with downstream application of MSC culture,expansion and tissue engineering.
文摘Microcarriers containing cellulose-derived materials have been successfully applied to enhance the growth of anchorage-dependent cells maintained especially in bioreactors.By replacing microcarriers with nanocarriers containing dextran,we hypothesized that the density of the anchorage-dependent cells would rise dramatically because the decreased particle size and associated enhancement in surface to volume ratios of nanoparticles contained within the nanoemulsion-based nanocarriers would increase the number of dextran molecules for the anchorage-dependent cells to attach to.Our studies utilized self-assembly nanoemulsions(SANE)formed by a modified phase inversion temperature(PIT)process to produce dextran oil and surfactant-containing nanocarriers having mean particle sizes of 26 nm compared to microcarriers which were greater than 6000 nm.Our results demonstrated that dextran-containing nanocarriers allowed up to 10 fold greater cell density,12% more media lactate concentration,83%higher cell lysate protein and 59% greater glucose concentration,used as a measure of polymer levels in the nanocarriers compared to microcarriers.In conclusion,nanocarriers with increased numbers of dextran molecules,developed in these studies may be useful to further increase the production of anchorage-dependent animal cell-derived products or production of mass cell growth for other applications.
