Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.
- MeSH
- akrylové pryskyřice * chemie MeSH
- diferenciální skenovací kalorimetrie MeSH
- difrakce rentgenového záření MeSH
- hydrogely * chemie MeSH
- koncentrace vodíkových iontů MeSH
- králíci MeSH
- lékové transportní systémy MeSH
- léky s prodlouženým účinkem chemie farmakokinetika MeSH
- mikroskopie elektronová rastrovací MeSH
- nosiče léků chemie MeSH
- poloxamer * chemie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- termogravimetrie MeSH
- timolol * aplikace a dávkování farmakokinetika chemie MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This article presents a method for producing hydrogel dressings using high methylated pectin from apples or citrus, doped with the antiseptic agent, octenidine dihydrochloride. Octenidine was incorporated in-situ during the polymer crosslinking. The pectins were characterized by their varying molecular weight characteristics, monosaccharide composition, and degree of esterification (DE). The study assessed the feasibility of producing biologically active hydrogels with pectin and delved into how the polymer's characteristics affect the properties of the resulting dressings. The structure evaluation of hydrogel materials showed interactions between individual components of the system and their dependence on the type of used pectin. Both the antimicrobial properties and cytotoxicity of the dressings were evaluated. The results suggest that the primary determinants of the functional attributes of the hydrogels are the molecular weight characteristics and the DE of the pectin. As these values rise, there is an increase in polymer-polymer interactions, overshadowing polymer-additive interactions. This intensification strengthens the mechanical and thermal stability of the hydrogels and enhances the release of active components into the surrounding environment. Biological evaluations demonstrated the ability of octenidine to be released from the dressings and effectively inhibit the growth of microbial pathogens.
- MeSH
- antiinfekční látky lokální * chemie farmakologie MeSH
- Citrus chemie MeSH
- hydrogely * chemie farmakologie MeSH
- iminy * chemie MeSH
- lidé MeSH
- Malus chemie MeSH
- mikrobiální testy citlivosti MeSH
- molekulová hmotnost MeSH
- obvazy * MeSH
- pektiny * chemie farmakologie MeSH
- pyridiny * chemie farmakologie MeSH
- Staphylococcus aureus účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Repairing and regenerating damaged tissues or organs, and restoring their functioning has been the ultimate aim of medical innovations. 'Reviving healthcare' blends tissue engineering with alternative techniques such as hydrogels, which have emerged as vital tools in modern medicine. Additive manufacturing (AM) is a practical manufacturing revolution that uses building strategies like molding as a viable solution for precise hydrogel manufacturing. Recent advances in this technology have led to the successful manufacturing of hydrogels with enhanced reproducibility, accuracy, precision, and ease of fabrication. Hydrogels continue to metamorphose as the vital compatible bio-ink matrix for AM. AM hydrogels have paved the way for complex 3D/4D hydrogels that can be loaded with drugs or cells. Bio-mimicking 3D cell cultures designed via hydrogel-based AM is a groundbreaking in-vivo assessment tool in biomedical trials. This brief review focuses on preparations and applications of additively manufactured hydrogels in the biomedical spectrum, such as targeted drug delivery, 3D-cell culture, numerous regenerative strategies, biosensing, bioprinting, and cancer therapies. Prevalent AM techniques like extrusion, inkjet, digital light processing, and stereo-lithography have been explored with their setup and methodology to yield functional hydrogels. The perspectives, limitations, and the possible prospects of AM hydrogels have been critically examined in this study.
- MeSH
- 3D tisk MeSH
- bioprinting metody MeSH
- buněčné kultury MeSH
- hydrogely * chemie MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- techniky 3D buněčné kultury metody MeSH
- tkáňové inženýrství * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Branched copolymer surfactants (BCS) containing thermoresponsive polymer components, hydrophilic components, and hydrophobic termini allow the formation of emulsions which switch from liquid at room temperature to a gel state upon heating. These materials have great potential as in situ gel-forming dosage forms for administration to external and internal body sites, where the emulsion system also allows effective solubilisation of a range of drugs with different chemistries. These systems have been reported previously, however there are many challenges to translation into pharmaceutical excipients. To transition towards this application, this manuscript describes the evaluation of a range of pharmaceutically-relevant oils in the BCS system as well as evaluation of surfactants and polymeric/oligomeric additives to enhance stability. Key endpoints for this study are macroscopic stability of the emulsions and rheological response to temperature. The effect of an optimal additive (methylcellulose) on the nanoscale processes occurring in the BCS-stabilised emulsions is probed by small-angle neutron scattering (SANS) to better comprehend the system. Overall, the study reports an optimal BCS/methylcellulose system exhibiting sol-gel transition at a physiologically-relevant temperature without macroscopic evidence of instability as an in situ gelling dosage form.
Bone tissue engineering strategy involves the 3D scaffolds and appropriate cell types promoting the replacement of the damaged area. In this work, we aimed to develop a fast and reliable clinically relevant protocol for engineering viable bone grafts, using cryopreserved adipose tissue-derived mesenchymal stromal cells (MSCs) and composite 3D collagen-nano-hydroxyapatite (nanoHA) scaffolds. Xeno- and DMSO-free cryopreserved MSCs were perfusion-seeded into the biomimetic collagen/nanoHA scaffolds manufactured by cryotropic gelation and their osteoregenerative potential was assessed in vitro and in vivo. Cryopreserved MSCs retained the ability to homogenously repopulate the whole volume of the scaffolds during 7 days of post-thaw culture. Moreover, the scaffold provided a suitable microenvironment for induced osteogenic differentiation of cells, confirmed by alkaline phosphatase activity and mineralization. Implantation of collagen-nanoHA cryogels with cryopreserved MSCs accelerated woven bone tissue formation, maturation of bone trabeculae, and vascularization of femur defects in immunosuppressed rats compared to cell-free collagen-nanoHA scaffolds. The established combination of xeno-free cell culture and cryopreservation techniques together with an appropriate scaffold design and cell repopulation approach accelerated the generation of viable bone grafts.
- MeSH
- buněčná diferenciace MeSH
- kolagen farmakologie MeSH
- kryogely * MeSH
- kryoprezervace MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- mezenchymální kmenové buňky * metabolismus MeSH
- osteogeneze MeSH
- proliferace buněk MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The design of improved biopolymeric based hydrogel materials with high load-capacity to serve as biocompatible drug carriers is a challenging task with vital implications in health sciences. In this work, chitosan crosslinked dialdehyde xanthan gum interpenetrated hydroxypropyl methylcellulose gels were developed for the controlled delivery of different antibiotic drugs including ampicillin, minocycline and rifampicin. The prepared hydrogel scaffolds were characterized by rheology method, FTIR, SEM, TGA and compression analysis. In addition, gelation kinetics, swelling, in vitro degradation and drug release rate were studied under simulated gastrointestinal fluid conditions of pH 2.0 and 7.4 at 37 °C. Results demonstrated the gel composition and structure affected drug release kinetics. The release study showed more than 50% cumulative release within 24 h for all investigated antibiotic drugs. In vitro cell cytocompatibility using mouse embryonic fibroblast cell lines depicted ≥80% cell viability, indicating the gels are non-toxic. Finally, the antibacterial activity of loaded gels was evaluated against Gram-negative and positive bacteria (Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia), which correlated well with swelling and drug release results. Overall, the present study demonstrated that the produced hydrogel scaffolds serves as promising material for controlled antibiotic delivery towards microbial growth inhibition.
- MeSH
- ampicilin farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální polysacharidy chemie MeSH
- biokompatibilní materiály chemie MeSH
- buněčné linie MeSH
- chitosan chemie MeSH
- deriváty hypromelózy chemie MeSH
- Escherichia coli účinky léků MeSH
- fibroblasty MeSH
- hydrogely chemická syntéza chemie farmakokinetika toxicita MeSH
- koncentrace vodíkových iontů MeSH
- mikrobiální testy citlivosti MeSH
- mikroskopie elektronová rastrovací MeSH
- minocyklin farmakologie MeSH
- myši MeSH
- nosiče léků chemie MeSH
- reologie MeSH
- rifampin farmakologie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Staphylococcus aureus účinky léků MeSH
- termogravimetrie MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Superporous poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate) (P(HEMA-AEMA)) hydrogel scaffolds are designed for in vitro 3D culturing of leukemic B cells. Hydrogel porosity, which influences cell functions and growth, is introduced by adding ammonium oxalate needle-like crystals in the polymerization mixture. To improve cell vitality, cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide is immobilized on the N-(γ-maleimidobutyryloxy)succinimide-activated P(HEMA-AEMA) hydrogels via reaction of SH with maleimide groups. This modification is especially suitable for the survival of primary chronic lymphocytic leukemia cells (B-CLLs) in 3D cell culture. No other tested stimuli (interleukin-4, CD40 ligand, or shaking) can further improve B-CLL survival or metabolic activity. Both unmodified and RGDS-modified P(HEMA-AEMA) scaffolds serve as a long-term (70 days) 3D culture platforms for HS-5 and M2-10B4 bone marrow stromal cell lines and MEC-1 and HG-3 B-CLL cell lines, although the adherent cells retain their physiological morphologies, preferably on RGDS-modified hydrogels. Moreover, the porosity of hydrogels allows direct cell lysis, followed by efficient DNA isolation from the 3D-cultured cells. P(HEMA-AEMA)-RGDS thus serves as a suitable 3D in vitro leukemia model that enables molecular and metabolic assays and allows imaging of cell morphology, interactions, and migration by confocal microscopy. Such applications can prospectively assist in testing of drugs to treat this frequently recurring or refractory cancer.
- MeSH
- buněčné kultury metody MeSH
- chronická lymfatická leukemie * MeSH
- hydrogely chemie MeSH
- lidé MeSH
- mezenchymální kmenové buňky MeSH
- nádorové buněčné linie MeSH
- oligopeptidy MeSH
- poréznost MeSH
- sukcinimidy chemie MeSH
- tkáňové podpůrné struktury chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The incorporation of the RGD peptide (arginine-glycine-aspartate) into biomaterials has been proposed to promote cell adhesion to the matrix, which can influence and control cell behaviour and function. While many studies have utilised RGD modified biomaterials for cell delivery, few have examined its effect under the condition of reduced oxygen and nutrients, as found at ischaemic injury sites. Here, we systematically examine the effect of RGD on hMSCs in hyaluronic acid (HA) hydrogel under standard and ischaemic culture conditions, to elucidate under what conditions RGD has beneficial effects over unmodified HA and its effectiveness in improving cell viability. Results demonstrate that under standard culture conditions, RGD significantly increased hMSC spreading and the release of vascular endothelial factor-1 (VEGF) and monocyte chemoattractant factor-1 (MCP-1), compared to unmodified HA hydrogel. As adhesion is known to influence cell survival, we hypothesised that cells in RGD hydrogels would exhibit increased cell viability under ischaemic culture conditions. However, results demonstrate that cell viability and protein release was comparable in both RGD modified and unmodified HA hydrogels. Confocal imaging revealed cellular morphology indicative of weak cell adhesion. Subsequent investigations found that RGD was could exert positive effects on encapsulated cells under ischaemic conditions but only if hMSCs were pre-cultured under standard conditions to allow strong adhesion to RGD before exposure. Together, these results provide novel insight into the value of RGD introduction and suggest that the adhesion of hMSCs to RGD prior to delivery could improve survival and function at ischaemic injury sites. STATEMENT OF SIGNIFICANCE: The development of a biomaterial scaffold capable of maintaining cell viability while promoting cell function is a major research goal in the field of cardiac tissue engineering. This study confirms the suitability of a modified HA hydrogel whereby stem cells in the modified hydrogel showed significantly greater cell spreading and protein secretion compared to cells in the unmodified HA hydrogel. A pre-culture period allowing strong adhesion of the cells to the modified hydrogel was shown to improve cell survival under conditions that mimic the myocardium post-MI. This finding may have a significant impact on the use and timelines of modifications to improve stem cell survival in harsh environments like the injured heart.
- MeSH
- buněčná adheze účinky léků MeSH
- buněčné kultury MeSH
- hydrogely chemie MeSH
- hypoxie buňky fyziologie MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie fyziologie MeSH
- oligopeptidy chemie MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
High risk Neuroblastoma (NB) includes aggressive, metastatic solid tumors of childhood. The survival rate improved only modestly, despite the use of combination therapies including novel immunotherapies based on the antibody-mediated targeting of tumor-associated surface ligands. Treatment failures may be due to the lack of adequate in vitro models for studying, in a given patient, the efficacy of potential therapeutics, including those aimed to enhance anti-tumor immune responses. We here propose a 3D alginate-based hydrogel as extracellular microenvironment to evaluate the effects of the three-dimensionality on biological and immunological properties of NB cells. NB cell lines grown within the 3D alginate spheres presented spheroid morphology, optimal survival, and proliferation capabilities, and a reduced sensitivity to the cytotoxic effect of imatinib mesylate. 3D cultured NB cells were also evaluated for the constitutive and IFN-γ-induced expression of surface molecules capable of tuning the anti-tumor activity of NK cells including immune checkpoint ligands. In particular, IFN-γ induced de novo expression of high amounts of HLA-I molecules, which protected NB cells from the attack mediated by KIR/KIR-L matched NK cells. Moreover, in the 3D alginate spheres, the cytokine increased the expression of the immune checkpoint ligands PD-Ls and B7-H3 while virtually abrogating that of PVR, a ligand of DNAM-1 activating receptor, whose expression correlates with high susceptibility to NK-mediated killing. Our 3D model highlighted molecular features that more closely resemble the immunophenotypic variants occurring in vivo and not fully appreciated in classical 2D culture conditions. Thus, based on our results, 3D alginate-based hydrogels might represent a clinical-relevant cell culture platform where to test the efficacy of personalized therapeutic approaches aimed to optimize the current and innovative immune based therapies in a very systematic and reliable way.
- MeSH
- algináty MeSH
- biologické modely MeSH
- buňky NK imunologie MeSH
- hydrogely * MeSH
- imatinib mesylát farmakologie MeSH
- imunofenotypizace MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- neuroblastom * farmakoterapie imunologie patologie MeSH
- proliferace buněk MeSH
- protinádorové látky farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Fabrication of porous and biologically inspired biomaterials that mimic the formation of microstructural structures of nacre in the form of calcite (CaCO3) and evaluation of the biocompatibility of such organic-inorganic composite scaffold for bone tissue engineering, are focus of this paper. Nacre's self-assembly characteristics are concerned about the development of calcite filled biomineralized scaffold following the nature based biomineralization process and biomimetic applications. The PVP-CMC hydrogel film, comprised of PVP:0.2, CMC:0.8, PEG:1.0, Agar:2.0, Glycerene:1.0 and water:95.0 w/v%; acts as catalyst and template for the nucleation and growth of the inorganic CaCO3 within the scaffold. The PVP-CMC hydrogel (in the dry state) was immersed in ionic solutions (g/100 ml) of Na2CO3 and CaCl2·H2O in different concentrations sets i.e. Set-1: 10.50/14.70; Set-2: 5.25/7.35; Set-3: 4.20/5.88; Set-4: 2.10/2.94; Set-5: 1.05/1.47, Set-6: 0.55/0.55 for 90 min. As a result, "PVP-CMC-CaCO3" hydrogel scaffold was fabricated having bio-inspired structural and functional properties. Cell proliferation and cell viability were examined until 7 days in the presence of "PVP-CMC-CaCO3" scaffolds using permanent cell lines MG63 (human osteosarcoma), L929 (murine fibroblasts) as well as cultures from mouse bone explants (CC-MBE), confirmed that the said hydrogel scaffolds are biocompatible. But, from mechanical strength as well as biocompatibility point of view, scaffolds prepared in Set-1 to 3 ionic solutions were superior. In conclusion, these three calcite filled hydrogel scaffolds are recommended and can be used for osseointegration.
- MeSH
- biokompatibilní materiály chemie MeSH
- buněčné linie MeSH
- difrakce rentgenového záření MeSH
- hydrogely chemie MeSH
- mikroskopie elektronová rastrovací MeSH
- myši MeSH
- osteointegrace fyziologie MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury chemie MeSH
- viabilita buněk fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
