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1.
J Vis Exp ; (207)2024 May 03.
Article in English | MEDLINE | ID: mdl-38767380

ABSTRACT

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.


Subject(s)
Bioprinting , Carrageenan , Carrageenan/chemistry , Bioprinting/methods , Microgels/chemistry , Printing, Three-Dimensional , Tissue Engineering/methods , Hydrogels/chemistry , Tissue Scaffolds/chemistry , Animals , Humans
2.
J Nanobiotechnology ; 22(1): 241, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735933

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.


Subject(s)
Fatty Acids, Volatile , Gastrointestinal Microbiome , Limosilactobacillus reuteri , Probiotics , Gastrointestinal Microbiome/drug effects , Probiotics/pharmacology , Humans , Fatty Acids, Volatile/metabolism , Animals , Limosilactobacillus reuteri/metabolism , Mice , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Administration, Oral , Colorectal Neoplasms/drug therapy , Cell Line, Tumor , Receptors, G-Protein-Coupled/metabolism , Microgels/chemistry , Mice, Inbred BALB C , Butyric Acid/pharmacology , Butyric Acid/metabolism
3.
Int J Biol Macromol ; 268(Pt 1): 131899, 2024 May.
Article in English | MEDLINE | ID: mdl-38677703

ABSTRACT

Emerging food processing technologies provide broader avenues for enhancing probiotic delivery systems. In this study, the new Fu brick tea polysaccharide (FBTP) was extracted and combined with cold plasma-modified alginate nano-montmorillonite (AMT) to prepare microgels by ionic gelation to improve the viability of encapsulated Lactobacillus kefiranofaciens JKSP109. Results showed that cold plasma treatment for 3 min changed the surface charge of AMT biopolymer solution, and FBTP addition reduced the particle size to the lowest of 223 ± 5.50 nm. Morphological analysis showed that the AMT treated with cold plasma for 3 min and FBTP (C3AMT + FBTP) formed a dense microgel through electrostatic interaction, and the probiotics were randomly distributed in their internal polysaccharide network, as well as the interlayer and surrounding of nanoparticles. The probiotics immobilized in C3AMT + FBTP microgel exhibited the highest viability (8.48 ± 0.03 log CFU/g) and colonic colonization after exposure to simulated gastrointestinal conditions. In addition, the good antioxidant activity of FBTP reduced the loss of probiotic viability during storage, with only 2.58 log CFU/g decreased after 4 weeks. Therefore, such probiotic products enriched with natural bioactive ingredients can be developed as a potential functional food additive.


Subject(s)
Alginates , Microgels , Polysaccharides , Probiotics , Tea , Alginates/chemistry , Tea/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Microgels/chemistry , Microbial Viability/drug effects , Plasma Gases/pharmacology , Plasma Gases/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Lactobacillus , Particle Size
4.
Int J Biol Macromol ; 268(Pt 1): 131594, 2024 May.
Article in English | MEDLINE | ID: mdl-38621568

ABSTRACT

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.


Subject(s)
Alginates , Chitosan , Human Umbilical Vein Endothelial Cells , Nerve Regeneration , Schwann Cells , Chitosan/chemistry , Chitosan/pharmacology , Alginates/chemistry , Alginates/pharmacology , Animals , Humans , Rats , Nerve Regeneration/drug effects , Schwann Cells/drug effects , Microgels/chemistry , Peripheral Nerve Injuries/drug therapy , Peripheral Nerve Injuries/therapy , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor A/metabolism , Tissue Scaffolds/chemistry , Methacrylates/chemistry , Methacrylates/pharmacology , Cell Movement/drug effects
5.
J Mater Chem B ; 12(19): 4736-4747, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38660955

ABSTRACT

Rapid removal of toxic substances is crucial to restore the normal functions of our body and ensure survival. Due to their high substrate specificity and catalytic efficiency, enzymes are unique candidates to deplete toxic compounds. While enzymes display several limitations including low stability and high immunogenicity, these can be overcome by entrapping them in a diverse range of carriers. The resulting micro/nanoreactors shield the enzymes from their surroundings, preventing their misfolding or denaturation thus allowing them to conduct their function. The micro/nanoreactors must circulate in the blood stream for extended periods of time to ensure complete depletion of the toxic agents. Surprisingly, while it is widely acknowledged that non-spherical carriers exhibit longer residence time in the bloodstream than their spherical counterparts, so far, all the reported micro/nanoreactors have been assembled with a spherical architecture. Herein, we address this important issue by pioneering the first shape-specific microreactors. We use UV-assisted punching to create rod-like microgel shapes with dimensions of 8 µm × 1 µm × 2 µm and demonstrate their biocompatibility by conducting hemolysis and cell viability assays with a macrophage and an endothelial cell line. Upon encapsulation of the model enzyme ß-lactamase, the successful fabrication of rod-shaped microreactors is demonstrated by their ability to convert the yellow nitrocefin substrate into its hydrolyzed product.


Subject(s)
Microgels , Humans , Microgels/chemistry , Cell Survival/drug effects , Animals , Mice , Hemolysis , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Biocompatible Materials/pharmacology , Particle Size , Surface Properties
6.
Food Chem ; 449: 139187, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38604029

ABSTRACT

Pickering emulsions stabilized by protein particles are of great interest for use in real food systems. This study was to investigate the properties of microgel particles prepared from different plant proteins, i.e., soybean protein isolate (SPI), pea protein isolate (PPI), mung bean protein isolate (MPI), chia seed protein isolate (CSPI), and chickpea protein isolate (CPI). MPI protein particles had most desirable Pickering emulsion forming ability. The particles of SPI and PPI had similar particle size (316.23 nm and 294.80 nm) and surface hydrophobicity (2238.40 and 2001.13) and emulsion forming ability, while the CSPI and CPI particle stabilized emulsions had the least desirable properties. The MPI and PPI particle stabilized Pickering emulsions produced better quality ice cream than the one produced by SPI particle-stabilized emulsions. These findings provide insight into the properties of Pickering emulsions stabilized by different plant protein particles and help expand their application in emulsions and ice cream.


Subject(s)
Emulsions , Particle Size , Plant Proteins , Emulsions/chemistry , Plant Proteins/chemistry , Microgels/chemistry , Hydrophobic and Hydrophilic Interactions , Ice Cream/analysis , Cicer/chemistry , Vigna/chemistry
7.
Biomater Adv ; 159: 213805, 2024 May.
Article in English | MEDLINE | ID: mdl-38457904

ABSTRACT

Bone defects may occur in different sizes and shapes due to trauma, infections, and cancer resection. Autografts are still considered the primary treatment choice for bone regeneration. However, they are hard to source and often create donor-site morbidity. Injectable microgels have attracted much attention in tissue engineering and regenerative medicine due to their ability to replace inert implants with a minimally invasive delivery. Here, we developed novel cell-laden bioprinted gelatin methacrylate (GelMA) injectable microgels, with controllable shapes and sizes that can be controllably mineralized on the nanoscale, while stimulating the response of cells embedded within the matrix. The injectable microgels were mineralized using a calcium and phosphate-rich medium that resulted in nanoscale crystalline hydroxyapatite deposition and increased stiffness within the crosslinked matrix of bioprinted GelMA microparticles. Next, we studied the effect of mineralization in osteocytes, a key bone homeostasis regulator. Viability stains showed that osteocytes were maintained at 98 % viability after mineralization with elevated expression of sclerostin in mineralized compared to non-mineralized microgels, showing that mineralization can effectively enhances osteocyte maturation. Based on our findings, bioprinted mineralized GelMA microgels appear to be an efficient material to approximate the bone microarchitecture and composition with desirable control of sample injectability and polymerization. These bone-like bioprinted mineralized biomaterials are exciting platforms for potential minimally invasive translational methods in bone regenerative therapies.


Subject(s)
Gelatin , Microgels , Gelatin/pharmacology , Gelatin/chemistry , Biocompatible Materials , Methacrylates/chemistry
8.
ACS Biomater Sci Eng ; 10(4): 2177-2187, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38466617

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of all pancreatic cancer cases. Five-year survival rates have remained below 12% since the 1970s, in part due to the difficulty in detection prior to metastasis (migration and invasion into neighboring organs and glands). Mechanical memory is a concept that has emerged over the past decade that may provide a path toward understanding how invading PDAC cells "remember" the mechanical properties of their diseased ("stiff", elastic modulus, E ≈ 10 kPa) microenvironment even while invading a healthy ("soft", E ≈ 1 kPa) microenvironment. Here, we investigated the role of mechanical priming by culturing a dilute suspension of PDAC (FG) cells within a 3D, rheologically tunable microgel platform from hydrogels with tunable mechanical properties. We conducted a suite of acute (short-term) priming studies where we cultured PDAC cells in either a soft (E ≈ 1 kPa) or stiff (E ≈ 10 kPa) environment for 6 h, then removed and placed them into a new soft or stiff 3D environment for another 18 h. Following these steps, we conducted RNA-seq analyses to quantify gene expression. Initial priming in the 3D culture showed persistent gene expression for the duration of the study, regardless of the subsequent environments (stiff or soft). Stiff 3D culture was associated with the downregulation of tumor suppressors (LATS1, BCAR3, CDKN2C), as well as the upregulation of cancer-associated genes (RAC3). Immunofluorescence staining (BCAR3, RAC3) further supported the persistence of this cellular response, with BCAR3 upregulated in soft culture and RAC3 upregulated in stiff-primed culture. Stiff-primed genes were stratified against patient data found in The Cancer Genome Atlas (TCGA). Upregulated genes in stiff-primed 3D culture were associated with decreased survival in patient data, suggesting a link between patient survival and mechanical priming.


Subject(s)
Carcinoma, Pancreatic Ductal , Microgels , Pancreatic Neoplasms , Humans , Cell Line, Tumor , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Hydrogels , Tumor Microenvironment/genetics
9.
Biofabrication ; 16(2)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38471160

ABSTRACT

Bioprinting has evolved into a thriving technology for the fabrication of cell-laden scaffolds. Bioinks are the most critical component for bioprinting. Recently, microgels have been introduced as a very promising bioink, enabling cell protection and the control of the cellular microenvironment. However, the fabrication of the bioinks involves the microfluidic production of the microgels, with a subsequent multistep process to obtain the bioink, which so far has limited its application potential. Here we introduce a direct coupling of microfluidics and 3D-printing for the continuous microfluidic production of microgels with direct in-flow printing into stable scaffolds. The 3D-channel design of the microfluidic chip provides access to different hydrodynamic microdroplet formation regimes to cover a broad range of droplet and microgel diameters. After exiting a microtubing the produced microgels are hydrodynamically jammed into thin microgel filaments for direct 3D-printing into two- and three-dimensional scaffolds. The methodology enables the continuous on-chip encapsulation of cells into monodisperse microdroplets with subsequent in-flow cross-linking to produce cell-laden microgels. The method is demonstrated for different cross-linking methods and cell lines. This advancement will enable a direct coupling of microfluidics and 3D-bioprinting for scaffold fabrication.


Subject(s)
Bioprinting , Microgels , Tissue Scaffolds , Printing, Three-Dimensional , Microfluidics , Cell Line , Tissue Engineering , Hydrogels
10.
Biomaterials ; 307: 122534, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38518589

ABSTRACT

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 µm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.


Subject(s)
Microgels , Myocardial Infarction , Humans , Reactive Oxygen Species , Myocardial Infarction/drug therapy , T-Lymphocytes, Regulatory , Microfluidics
11.
Biomaterials ; 307: 122535, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38518590

ABSTRACT

Arrest of bleeding usually applies clotting agents to trigger coagulation procedures or adhesives to interrupt blood flow through sealing the vessel; however, the efficiency is compromised. Here, we propose a concept of integration of hemostasis and adhesion via yam mucus's microgels. The mucus microgels exhibit attractive attributes of hydrogel with uniform size and shape. Their shear-thinning, self-healing and strong adhesion make them feasible as injectable bioadhesion. Exceptionally, the blood can trigger the microgels' gelation with the outcome of super extensibility, which leads to the microgels a strong hemostatic agent. We also found a tight gel adhesive layer formed upon microgels' contacting the blood on the tissue, where there is the coagulation factor XIII triggered to form a dense three-dimensional fibrin meshwork. The generated structures show that the microgels look like hard balls in the dispersed phase into the blood-produced fibrin mesh of a soft net phase. Both phases work together for a super-extension gel. We demonstrated the microgels' fast adhesion and hemostasis in the livers and hearts of rabbits and mini pigs. The microgels also promoted wound healing with good biocompatibility and biodegradability.


Subject(s)
Hemostatics , Microgels , Swine , Animals , Rabbits , Hemostatics/pharmacology , Swine, Miniature , Hemostasis , Fibrin/pharmacology , Hydrogels/chemistry
12.
Methods Mol Biol ; 2784: 271-284, 2024.
Article in English | MEDLINE | ID: mdl-38502492

ABSTRACT

Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.


Subject(s)
Carcinoma , Microgels , Uterine Cervical Neoplasms , Female , Humans , DNA , DNA Damage , DNA Probes/genetics , DNA, Single-Stranded , In Situ Hybridization, Fluorescence/methods , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology
13.
Adv Sci (Weinh) ; 11(15): e2303128, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38348560

ABSTRACT

Nonalcoholic fatty liver disease affects 30% of the United States population and its progression can lead to nonalcoholic steatohepatitis (NASH), and increased risks for cirrhosis and hepatocellular carcinoma. NASH is characterized by a highly heterogeneous liver microenvironment created by the fibrotic activity of hepatic stellate cells (HSCs). While HSCs have been widely studied in 2D, further advancements in physiologically relevant 3D culture platforms for the in vitro modeling of these heterogeneous environments are needed. In this study, the use of stiffness-variable, extracellular matrix (ECM) protein-conjugated polyethylene glycol microgels as 3D cell culture scaffolds to modulate HSC activation is demonstrated. These microgels as a high throughput ECM screening system to identify HSC matrix remodeling and metabolic activities in distinct heterogeneous microenvironmental conditions are further employed. The 6 kPa fibronectin microgels are shown to significantly increase HSC matrix remodeling and metabolic activities in single or multiple-component microenvironments. Overall, heterogeneous microenvironments consisting of multiple distinct ECM microgels promoted a decrease in HSC matrix remodeling and metabolic activities compared to homogeneous microenvironments. The study envisions this ECM screening platform being adapted to a broad number of cell types to aid the identification of ECM microenvironments that best recapitulate the desired phenotype, differentiation, or drug efficacy.


Subject(s)
Liver Neoplasms , Microgels , Non-alcoholic Fatty Liver Disease , Humans , Hepatic Stellate Cells/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Fibrosis , Liver Neoplasms/metabolism , Tumor Microenvironment
14.
ACS Appl Mater Interfaces ; 16(9): 11860-11871, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38410836

ABSTRACT

In this research, we report dextrin-based biodegradable microgels (PDXE MGs) having phosphate-based cross-linking units for slow release of urea and a potential P source to improve fertilization. PDXE MGs (∼200 nm) are synthesized by cross-linking the lauroyl-functionalized dextrin chains with sodium tripolyphosphate. The developed PDXE MGs exhibit high loading (∼10%) and encapsulation efficiency (∼88%) for urea. It is observed that functionalization of PDXE MGs with lauroyl chains slows down the release of urea (90% in ∼24 days) as compared to nonfunctionalized microgels (PDX MGs) (99% in ∼17 days) in water. Further studies of the developed formulation display that Urea@PDXE MGs significantly boost maize seed germination and overall plant growth as compared to pure urea fertilizer. Moreover, analysis of maize leaves obtained from plants treated with Urea@PDXE MGs reveals 3.5 ± 0.3% nitrogen content and 90 ± 0.7 mg/g chlorophyll content. These values are significantly higher than 1.4 ± 0.6% nitrogen content and 48 ± 0.05 mg/g chlorophyll content obtained by using bare urea. Further, acid phosphatase activity in roots is reduced upon treatment with PDXE MGs and Urea@PDXE MGs, suggesting the availability of P upon degradation of PDXE MGs by the amylase enzyme in soil. These experimental results present the developed microgel-based biodegradable formulation with a slow release feature as a potential candidate to move toward sustainable agriculture practices.


Subject(s)
Microgels , Fertilizers , Dextrins , Agriculture , Soil , Nitrogen , Urea , Zea mays , Chlorophyll
15.
Int J Biol Macromol ; 263(Pt 1): 129685, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38394762

ABSTRACT

Microfluidic systems are capable of producing microgels with a monodisperse size distribution and a spherical shape due to their laminar flow and superior flow. A significant challenge in producing these drug-carrying microgels is simultaneous drug loading into microgels. Various factors such as the type of polymer, the type of drug, the volume ratio of the drug to the polymer, and the geometry of the microfluidic system used to generate microgels can effectively address these challenges. The overall goal of this study was to produce mono-disperse drug-carrying microgels capable of controlled drug release. To achieve this goal, this study used a stream-focused microfluidic chip containing a coating current to prevent chip clogging. Alginate oxide was synthesized with a 30 % oxidation percentage. Alginate oxide, gelatin, and compositions of them with volume ratios of 50-50, 70-30, and 30-70, by determining their appropriate weight percentage, were used for the controlled release of letrozole. The properties of the produced microgels were measured through various tests such as drug release test, loading percentage, SEM, FTIR, swelling ratio, and dimensional stability. It was found that microgels made of a combination of alginate oxide-gelatin with volume ratios of 70-30 had a good swelling ratio and structural stability. The drug loading percentages for alginate, alginate oxide, and alginate oxide-gelatin with volume ratios of 50-50 and 30-70, respectively, were 56 %, 68 %, and 66 %, 61 % and the alginate oxide-gelatin with a volume ratio of 70-30 compared to other samples had over 70 % drug loading percentages. Furthermore, samples of alginate, alginate oxide, and alginate oxide-gelatin with volume ratios of 50-50 and 30-70 had 94 %, 63 %, 56 %, and 68 % drug release in 13 days, respectively. However, alginate oxide-gelatin with a volume ratio of 70-30 had a release rate of about 50 % in 13 days, which is a more controlled release for letrozole compared to the volume ratios of 50-50 and 30-70. Examining the drug release profile, it was concluded that drug release follows the Higuchi model and therefore follows Fick's first law of diffusion. It can be concluded that the combination of alginate oxide-gelatin produces more suitable microgels than alginate and alginate oxide for the controlled-release of letrozole. A comparison of microgels of alginate oxide and gelatin with volume ratios of 50-50 and 70-30 had better results for the cytotoxicity study compared to other samples.


Subject(s)
Microgels , Microfluidics , Gelatin/chemistry , Letrozole , Oxides , Delayed-Action Preparations , Alginates/chemistry , Polymers
16.
Int J Biol Macromol ; 262(Pt 1): 129684, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38307741

ABSTRACT

Incorporation of growth factors, signaling molecules and drugs can be vital for the success of tissue engineering in complex structures such as the dentoalveolar region. This has led to the development of a variety of drug release systems. This study aimed to develop pNIPAM-methylcellulose microgels with different synthesis parameters based on a 23 full factorial design of experiments for this application. Microgel properties, including volume phase transition temperature (VPTT), hydrodynamic size, drug loading and release, and cytocompatibility were systematically evaluated. The results demonstrated successful copolymerization and development of the microgels, a hydrodynamic size ranging from ∼200 to ∼500 nm, and VPTT in the range of 34-39 °C. Furthermore, loading of genipin, capable of inducing odontoblastic differentiation, and its sustained release over a week was shown in all formulations. Together, this can serve as a solid basis for the development of tunable drug-delivering pNIPAM-methylcellulose microgels for specific tissue engineering applications.


Subject(s)
Microgels , Gels/chemistry , Methylcellulose , Tissue Engineering , Transition Temperature
17.
Adv Mater ; 36(16): e2312559, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38266145

ABSTRACT

Abnormal silencing of fibroblast growth factor (FGF) signaling significantly contributes to joint dysplasia and osteoarthritis (OA); However, the clinical translation of FGF18-based protein drugs is hindered by their short half-life, low delivery efficiency and the need for repeated articular injections. This study proposes a CRISPR/Cas9-based approach to effectively activate the FGF18 gene of OA chondrocytes at the genome level in vivo, using chondrocyte-affinity peptide (CAP) incorporated hybrid exosomes (CAP/FGF18-hyEXO) loaded with an FGF18-targeted gene-editing tool. Furthermore, CAP/FGF18-hyEXO are encapsulated in methacrylic anhydride-modified hyaluronic (HAMA) hydrogel microspheres via microfluidics and photopolymerization to create an injectable microgel system (CAP/FGF18-hyEXO@HMs) with self-renewable hydration layers to provide persistent lubrication in response to frictional wear. Together, the injectable CAP/FGF18-hyEXO@HMs, combined with in vivo FGF18 gene editing and continuous lubrication, have demonstrated their capacity to synergistically promote cartilage regeneration, decrease inflammation, and prevent ECM degradation both in vitro and in vivo, holding great potential for clinical translation.


Subject(s)
Cartilage, Articular , Exosomes , Microgels , Osteoarthritis , Humans , Chondrocytes , Lubrication , Exosomes/metabolism , Gene Editing , Cartilage, Articular/metabolism , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Fibroblast Growth Factors/therapeutic use , Osteoarthritis/metabolism
18.
Int J Biol Macromol ; 261(Pt 1): 129749, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38281522

ABSTRACT

Natural polychromatic biomaterials (like carminic acid and gardenia yellow) possess coloring merits and functionality, but are instable under light and heat. Self-assembly of gelatin and polychromatic materials could be induced by carnosic acid inclusions, illustrating great potential in food application. Antioxidant properties, pigment retention rates, UV irradiation stability, rheological properties, and physical resistances (oil, ethanol, heat and microwave) of samples were improved by carnosic acid inclusions, owing to the newly formed hydrogen bonding and electrostatic interactions (UV spectrum, particle size, zeta potential, FTIR, XPS and SEM). The improved properties contributed to the 2D printed pattern stability and the applicability for producing specialized products with high printability and fastness. On the basis of Subtractive Color-Mixing Principle, further three-dimensional dyeing microgel systems were built and modulated; it could functionalize bean paste/carboxymethyl-cellulose food systems, maintain the excellent self-supporting ability & mechanical strength, and promote single/dual-nozzle 3D printing application. Therefore, the self-assembled gelatin/polychromatic materials/carnosic acid microgel samples could not only achieve outstanding 2D printed pattern stability, and could be also promisingly applied in single/dual-nozzle 3D printing for modern innovative, creative food fields.


Subject(s)
Abietanes , Microgels , Gelatin , Biocompatible Materials , Printing, Three-Dimensional
19.
Biomater Sci ; 12(8): 1950-1964, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38258987

ABSTRACT

Microgels have become a popular and powerful structural unit in the bioprinting field due to their advanced properties, ranging from the tiny size and well-connected hydrogel (nutrient) network to special rheological properties. Different microgels can be fabricated by a variety of fabrication methods including bulk crushing, auxiliary dripping, multiphase emulsion, and lithography technology. Traditionally, microgels can encapsulate specific cells and are used for in vitro disease models and in vivo organ regeneration. Furthermore, microgels can serve as a drug carrier to realize controlled release of drug molecules. Apart from being used as an independent application unit, recently, these microgels are widely applied as a specific bioink component in 3D bioprinting for in situ tissue repair or building special 3D structures. In this review, we introduce different methods used to generate microgels and the microgel-based bioink for bioprinting. Besides, the further tendency of microgel development in future is introduced and predicted to provide guidance for related researchers in exploring more effective ways to fabricate microgels and more potential bioprinting application cases as multifunctional bioink components.


Subject(s)
Bioprinting , Microgels , Microgels/chemistry , Tissue Engineering , Hydrogels/chemistry , Regeneration , Printing, Three-Dimensional , Tissue Scaffolds
20.
Adv Biol (Weinh) ; 8(4): e2300547, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38282178

ABSTRACT

Access to therapeutic strategies that counter cellular stress induced by reactive oxygen species (ROS) is an important, long-standing challenge. Here, the assembly of antioxidant artificial cells is based on alginate hydrogels equipped with non-native catalysts, namely platinum nanoparticles and an EUK compound. These artificial cells are able to preserve the viability and lower the intracellular ROS levels of challenged hepatic cells by removing peroxides from the extracellular environment. Conceptually, this strategy illustrates the potential use of artificial cells with a synthetic catalyst toward long-term support of hepatic cells and potentially other mammalian cells.


Subject(s)
Metal Nanoparticles , Microgels , Animals , Antioxidants/pharmacology , Reactive Oxygen Species , Peroxides , Platinum , Hepatocytes , Mammals
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