RESUMEN
Antibodies are widely used both in clinical practice and in research. However, the development of methods to increase the ratio of antibodies to recognize phosphorylated proteins remains challenging. In this study, we report a novel and useful method for the efficient production of antibodies for phosphorylated proteins. Based on our previously developed vaccine adjuvant Nap-GDFDFDY, we prepared hydrogels by the Ca2+-induced self-assembly of a phosphorylated peptide gelator Nap-GDFDFpDY. The hydrogel could protect phosphorylated antigens from being dephosphorylated by endogenous phosphatase, thus selectively increasing the ratio of the antibodies for phosphorylated proteins. Our study provides a useful strategy for the production of antibodies to recognize proteins with specific posttranslational modifications.
Asunto(s)
Anticuerpos/química , Anticuerpos/inmunología , Formación de Anticuerpos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Monoéster Fosfórico Hidrolasas/análisis , Monoéster Fosfórico Hidrolasas/inmunología , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/química , Monoéster Fosfórico Hidrolasas/metabolismo , FosforilaciónRESUMEN
Three-dimensional (3D) tissue models replicating liver architectures and functions are increasingly being needed for regenerative medicine. However, traditional studies are focused on establishing 2D environments for hepatocytes culture since it is challenging to recreate biodegradable 3D tissue-like architecture at a micro scale by using hydrogels. In this paper, we utilized a gelatin methacryloyl (GelMA) hydrogel as a matrix to construct 3D lobule-like microtissues for co-culture of hepatocytes and fibroblasts. GelMA hydrogel with high cytocompatibility and high structural fidelity was determined to fabricate hepatocytes encapsulated micromodules with central radial-type hole by photo-crosslinking through a digital micromirror device (DMD)-based microfluidic channel. The cellular micromodules were assembled through non-contact pick-up strategy relying on local fluid-based micromanipulation. Then the assembled micromodules were coated with fibroblast-laden GelMA, subsequently irradiated by ultraviolet for integration of the 3D lobule-like microtissues encapsulating multiple cell types. With long-term co-culture, the 3D lobule-like microtissues encapsulating hepatocytes and fibroblasts maintained over 90% cell viability. The liver function of albumin secretion was enhanced for the co-cultured 3D microtissues compared to the 3D microtissues encapsulating only hepatocytes. Experimental results demonstrated that 3D lobule-like microtissues fabricated by GelMA hydrogels capable of multicellular co-culture with high cell viability and liver function, which have huge potential for liver tissue engineering and regenerative medicine applications.
Asunto(s)
Gelatina/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hígado/efectos de los fármacos , Ingeniería de Tejidos/métodos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Fibroblastos/química , Fibroblastos/efectos de los fármacos , Gelatina/química , Gelatina/farmacología , Células Hep G2 , Hepatocitos/efectos de los fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Hígado/crecimiento & desarrollo , Medicina RegenerativaRESUMEN
Composite biomaterials offer a new approach for engineering novel, minimally-invasive scaffolds with properties that can be modified for a range of soft tissue applications. In this study, a new way of controlling the gelation of alginate hydrogels using Ga-based glass particles is presented. Through a comprehensive analysis, it was shown that the setting time, mechanical strength, stiffness and degradation properties of this composite can all be tailored for various applications. Specifically, the hydrogel generated through using a glass particle, wherein toxic aluminium is replaced with biocompatible gallium, exhibited enhanced properties. The material's stiffness matches that of soft tissues, while it displays a slow and tuneable gelation rate, making it a suitable candidate for minimally-invasive intra-vascular injection. In addition, it was also found that this composite can be tailored to deliver ions into the local cellular environment without affecting platelet adhesion or compromising viability of vascular cells in vitro.
Asunto(s)
Alginatos/química , Materiales Biocompatibles/química , Galio/química , Vidrio/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Alginatos/aislamiento & purificación , Alginatos/toxicidad , Animales , Aorta/citología , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/toxicidad , Bovinos , Supervivencia Celular/efectos de los fármacos , Fuerza Compresiva , Módulo de Elasticidad , Células Endoteliales/efectos de los fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/toxicidad , Miocitos del Músculo Liso/efectos de los fármacos , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
Bacterial infection is one of main causes that threaten global human health. Especially, antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) lead to high mortality rate and more expensive treatment cost. Here, a novel amino-acid-modified conjugated oligomer OTE-d-Phe was synthesized by modifying the side chain of conjugated oligo(thiophene ethynylene) with d-phenylalanine. By mixing 9-fluorenylmethyloxycarbonyl-l-phenylalanin (Fmoc-l-Phe) with OTE-d-Phe, a new and biocompatible low-molecular weight hydrogel (HG-2) was prepared through self-assembly. In solution, HG-2 can effectively capture bacteria spontaneously, such as Escherichia coli and MRSA. Most importantly, the hydrogel has specific and strong antibacterial activity against MRSA over methicillin-susceptible S. aureus, Staphylococcus epidermidis, and E. coli. Interestingly, when the hydrogel was put on a model surface, a piece of cloth, it also is able to selectively kill MRSA with low cell cytotoxicity. The antibacterial mechanism was investigated, and it demonstrated that the HG-2 interacts with and physically breaks the cell wall and membrane, which leads to MRSA death. Therefore, this new conjugated oligomer-based hydrogel provides promising applications in disinfection and therapy of MRSA in hospital and in community.
Asunto(s)
Antibacterianos/farmacología , Sinergismo Farmacológico , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Aminoácidos/efectos de los fármacos , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Pruebas de Sensibilidad Microbiana , Fenilalanina/química , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/patogenicidad , Tiofenos/síntesis química , Tiofenos/química , Tiofenos/farmacologíaRESUMEN
Self-healing hydrogels based on metal-ligand coordination chemistry provide new and exciting properties that improve injectability, rheological behaviors, and even biological functionalities. The inherent reversibility of coordination bonds improves on the covalent cross-linking employed previously, allowing for the preparation of completely self-healing hydrogels. In this article, recent advances in the development of this class of hydrogels are summarized and their applications in biology and medicine are discussed. Various chelating ligands such as bisphosphonate, catechol, histidine, thiolate, carboxylate, pyridines (including bipyridine and terpyridine), and iminodiacetate conjugated onto polymeric backbones, as well as the chelated metal ions and metal ions containing inorganic particles, which are used to form dynamic networks, are highlighted. This article provides general ideas and methods for the design of self-healing hydrogel biomaterials based on coordination chemistry.
Asunto(s)
Tecnología Biomédica , Complejos de Coordinación/química , Diseño de Fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Polímeros/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Ligandos , Polímeros/químicaRESUMEN
Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigenâ¯+â¯adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.
Asunto(s)
Alginatos/síntesis química , Preparaciones de Acción Retardada/química , Técnicas Analíticas Microfluídicas , Microesferas , Ovalbúmina/química , Alginatos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
A 3D hydrogel layer is probed by combining surface plasmon resonance with optical waveguide spectroscopy to detect biomolecules. A template terpolymer P(DMAAm-co-DMIAAm-co-VDMA) is synthesized via reversible addition-fragmentation chain-transfer polymerization. The terpolymer is then modified with an amino group bearing biotin to enable biomolecular recognition for streptavidin. A hydrogel thin layer is prepared onto a gold surface after spin-coating and photo-crosslinking of the modified polymer. Finally, the hydrogel is utilized to quantitatively detect streptavidin by using surface plasmon resonance-optical waveguide spectroscopy measurements.
Asunto(s)
Hidrogel de Polietilenoglicol-Dimetacrilato/química , Lactonas/química , Polímeros/síntesis química , Oro/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Estructura Molecular , Polimerizacion , Polímeros/química , Resonancia por Plasmón de Superficie , Propiedades de SuperficieRESUMEN
In this study, a simple yet versatile method is introduced to prepare a hyperbranched supramolecular polymer hydrogel by utilizing Type II photoinitiated self-condensing vinyl polymerization of N-acryloyl glycinamide, which can serve not only as an inimer providing branching sites, but also as a hydrogen-bonding cross-linker. The hyperbranched poly(N-acryloyl glycinamide) (HB-PNAGA) hydrogels demonstrate excellent mechanical performances with a tensile strength of 0.793-2.724 MPa, elongation at break of 203-902%, Young's modulus of 0.450-1.172 MPa, and maximal fracture energy of 2200 J m-2 , which are all superior to those of linear PNAGA hydrogels. The results indicate that the HB-PNAGA hydrogel is very stiff and tough due to much higher H-bonding cross-linking density formed in hyperbranched architecture. The high stiffness, toughness, and ease of preparation make these hyperbranched supramolecular hydrogels very attractive for application as soft supporting tissue replacements.
Asunto(s)
Reactivos de Enlaces Cruzados/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polímeros/química , Reactivos de Enlaces Cruzados/síntesis química , Glicina/análogos & derivados , Glicina/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Enlace de Hidrógeno , Sustancias Macromoleculares/síntesis química , Sustancias Macromoleculares/química , Estructura Molecular , Polimerizacion , Polímeros/síntesis química , Ingeniería de TejidosRESUMEN
Cell or tissue stretching and strain are present in any in vivo environment, but is difficult to reproduce in vitro. Here, we describe a simple method for casting a thin (about 500 µm) and soft (about 0.3 kPa) hydrogel of gelatin and a method for characterizing the mechanical properties of the hydrogel simply by changing pressure with a water column. The gelatin is crosslinked with mTransglutaminase and the area of the resulting hydrogel can be increased up 13-fold by increasing the radial water pressure. This is far beyond physiological stretches observed in vivo. Actuating the hydrogel with a radial force achieves both information about stiffness, stretchability, and contractability, which are relevant properties for tissue engineering purposes. Cells could be stretched and contracted using the gelatin membrane. Gelatin is a commonly used polymer for hydrogels in tissue engineering, and the discovered reversible stretching is particularly interesting for organ modeling applications.
Asunto(s)
Gelatina/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polímeros/química , Ingeniería de Tejidos , Gelatina/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Fenómenos Mecánicos , Membranas/química , Polímeros/síntesis química , Transglutaminasas/química , Agua/químicaRESUMEN
Herein, we report the successful synthesis of a series of poly (N-isopropylacrylamide) (PNIPA)/layered double hydroxides (LDHs)/nano-hydroxyapatite (nano-HA) hydrogels via in-situ radical polymerization. The internal morphology, thermo sensitivity, rheological properties, swelling behavior and hemocompatibility of the PNIPA/LDHs/HA composite hydrogels were systematically investigated. Results show that the hydrogels had a reversible sol-gel transformation around 33⯰C. Interactions between the positively charged LDHs and negatively charged nano-HA particles created a highly porous hydrogel network. The composite hydrogels exhibited excellent hemocompatibility, incredible mechanical toughness and reversible swelling/deswelling behavior. To our knowledge, this is the first reported study to use two types of inorganic nanoparticle with opposing charges as hydrogel crosslinking agents. Based on its properties, we expect this hydrogel has broad applications potential in tissue engineering, drug delivery and biosensor development.
Asunto(s)
Reactivos de Enlaces Cruzados/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanopartículas/química , Temperatura , Reactivos de Enlaces Cruzados/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
A highly competent material, based on poly lactic acid (PLLA) grafted hydroxypropyl guar gum (HPG-g-PLLA) and polypyrrole/carboxylated multiwalled carbon nanotube (PPy/C-MWCNT) composite of various binary composition and copolymer of one of these nanocomposites have been synthesized successfully by in-situ polymerization. The environmentally affable nanocomposites have been characterized by spectroscopy, microscopy and thermogravimetry. Cytotoxicity of bio-nanocomposite has been inquired by cell viability study, which reveals its eco-friendly nature. The electrochemical properties of the biomaterials have been appraised by cyclic voltammetric studies. The PPy/C-MWCNT composite having 1â¯wt% C-MWCNT appears as the optimum composition from electrochemical studies. The hydrogel nanocomposite (HPG-g-PLLA5/0.5) copolymer behaves as a super ordinate material than pure PPy and PPy/C-MWCNT in every aspect of electrochemical properties like current density, stability, processibility and reversibility. Moreover the hydrogel nanocomposite, making electrode fabrication more simple and binder-free, nullifies all the interfacial complications arising from binders as well.
Asunto(s)
Biopolímeros/química , Nanotubos de Carbono/química , Poliésteres/síntesis química , Polisacáridos/síntesis química , Galactanos/síntesis química , Galactanos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Mananos/síntesis química , Mananos/química , Nanocompuestos/química , Gomas de Plantas/síntesis química , Gomas de Plantas/química , Poliésteres/química , Polimerizacion , Polímeros/química , Polisacáridos/química , Pirroles/químicaRESUMEN
Extremely compressible hydrogels are fabricated in one pot via sulfonic-acid-modified graphitic carbon nitride (g-CN-AHPA) as a visible light photoinitiator and reinforcer. The hydrogels show unusual compressibility upon applied stress up to 12 MPa, presenting temporary physical deformation, and remain undamaged after stress removal despite their high water content (90 wt%). Cyclic compressibility proves the fatigue resistance of the covalently and electrostatically reinforced system that possesses tissue adhesive properties, shock resistance, cut resistance, and little to no toxicity.
Asunto(s)
Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nitrilos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Estructura Molecular , Electricidad EstáticaRESUMEN
Simplifying synthesis and administration process, improving photothermal agents' accumulation in tumors, and ensuring excellent biocompatibility and biodegradability are keys to promoting the clinical application of photothermal therapy. However, current photothermal agents have great difficulties in meeting the requirements of clinic drugs from synthesis to administration. Herein, we reported the in situ formation of a Ca2+/Mg2+ stimuli-responsive ICG-alginate hydrogel in vivo for localized tumor photothermal therapy. An ICG-alginate hydrogel can form by the simple introduction of Ca2+/Mg2+ into ICG-alginate solution in vitro, and the widely distributed divalent cations in organization in vivo enabled the in situ fabrication of the ICG-alginate hydrogel without the leakage of any agents by simple injection of ICG-alginate solution into the body of mice. The as-prepared ICG-alginate hydrogel not only owns good photothermal therapy efficacy and excellent biocompatibility but also exhibits strong ICG fixation ability, greatly benefiting the high photothermal agents' accumulation and minimizing the potential side effects induced by the diffusion of ICG to surrounding tissues. The in situ-fabricated ICG-alginate hydrogel was applied successfully in highly efficient PTT in vivo without obvious side effects. Besides, the precursor of the hydrogel, ICG and alginate, can be stored in a stable solid form, and only simple mixing and noninvasive injection are needed to achieve PTT in vivo. The proposed in situ gelation strategy using biocompatible components lays down a simple and mild way for the fabrication of high-performance PTT agents with the superiors in the aspects of synthesis, storage, transportation, and clinic administration.
Asunto(s)
Verde de Indocianina/uso terapéutico , Nanopartículas/química , Neoplasias/terapia , Fototerapia , Alginatos/química , Alginatos/farmacología , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/uso terapéutico , Plásticos Biodegradables/síntesis química , Plásticos Biodegradables/química , Plásticos Biodegradables/uso terapéutico , Colorantes/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Verde de Indocianina/síntesis química , Verde de Indocianina/química , Rayos Infrarrojos , Nanopartículas/uso terapéutico , Neoplasias/patología , Nanomedicina TeranósticaRESUMEN
BACKGROUND: In this study, central composite design was utilized for the optimization of genipin cross-linked chitosan/Eudragit®-L 100 interpenetrating hydrogel network films fabricated through solvent evaporation technique. METHODS: Hydrogel formulations were studied using response surface methodology; regression analysis and the surface plots were used to evaluate the effect of variables on T50% (the time for 50% of drug release) and dynamic swelling with optimum formulation selection. Initial burst release of drug was observed from the formulated hydrogels during the first 2 hours of dissolution at simulated gastric pH 1.2 and then slow release during the next 10 hours in the simulated intestinal fluid at pH 7.4. Different polymer ratios in formulation showed significant influence on T50% and dynamic swelling of hydrogel. The highest T50% was observed at 9.89 hour and dynamic swelling at 7.86 h. RESULT: It was observed that by changing the polymer ratio with cross-linker, release rate of metformin could be modified. Cross-linker also affects drug release rate, i.e. the release rate is decreased with the increase in its concentration. The physical state of hydrogel was investigated by scanning electron microscope. CONCLUSION: It indicated the uniform distribution of drug in hydrogel matrix system. Moreover, the presence of hydrogen and ionic bonds between polymers and crosslinking agent formed interpenetrating hydrogel network, likely responsible for increased value of T50%, as confirmed by FTIR. Acute oral toxicity study was performed to investigate the toxic effect of crosslinking agent and polymer used in formulations.
Asunto(s)
Acrilatos/química , Quitosano/química , Reactivos de Enlaces Cruzados/química , Liberación de Fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Iridoides/química , Metformina/química , Polímeros/química , Acrilatos/sangre , Animales , Quitosano/sangre , Concentración de Iones de Hidrógeno , Iridoides/sangre , Masculino , Metformina/sangre , Tamaño de la Partícula , Conejos , Análisis de Regresión , Propiedades de SuperficieRESUMEN
In tissue engineering there is growing interest in fabricating highly engineered platforms designed to instruct cells towards the synthesis of tissues that reproduce their natural counterpart. In this context, a fundamental factor to take into account is the control over the final tissue orientation, especially for what concerns the replication of load-bearing tissues whose functions are strictly related to their microstructural organization. Starting from this point, in this work we have engineered a gelatin-based hydrogel in order to be patterned by 2-photon polymerization (2PP) lithography for the fabrication of instructive free standing building blocks designed to produce anisotropic collagen-based µtissues. Biological results clearly highlighted the strong relationship between µtissue orientation and such topographies, which resulted in a crucial element in the production of highly anisotropic µtissues.
Asunto(s)
Matriz Extracelular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Gelatina/farmacología , Ingeniería de Tejidos , Células Cultivadas , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Fibroblastos/citología , Gelatina/síntesis química , Gelatina/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacología , Polimerizacion/efectos de los fármacos , Programas InformáticosRESUMEN
Silk fibroin (SF) hydrogel is a promising candidate in biomaterial field; however its application is quite limited by long-gelation time. In the present study, we developed a novel strategy named soft freezing to accelerate the process and control the sol-gel transition of SF protein. SF protein was induced to self-assembly by soft freezing process for achieving the reconstructed SF solution with metastable structure. It was found that the soft freezing process triggers the structural transition from random structure to ordered structure-rich conformation. Gelation kinetics showed that the gelation time of SF protein could be regulated by changing freezing time and initial concentration. The reconstructed SF solution allowed enhanced sol-gel transition within 6 hours, even at extremely low concentration. The attractive features of the method described here include the accelerated gelation, free of chemical agents, and reducing processing complexity. The SF solution with short gelation time will be applicable as cell encapsulation and injectable applications for tissue engineering and regenerative medicine, which greatly expand the applications of SF hydrogels.
Asunto(s)
Fibroínas/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Seda/química , Animales , Bombyx , Congelación , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Transición de FaseRESUMEN
A versatile double-network (DN) hydrogel with two noncovalent crosslinked networks is synthesized by multiple hydrogen bonding (H-bonding) interactions. The DN hydrogels are synthesized via a heating-cooling photopolymerization process by adding all reactants of agar, N-acryloyl glycinamide (NAGA) and N-benzylacrylamide (NBAA) monomers, UV initiators to a single water pot. Poly(N-acryloyl glycinamide-co-N-benzyl acrylamide) (P(NAGA-co-NBAA)) with a triple amide in one side group is synthesized via UV-light polymerization between NAGA and NBAA, forming a strong intermolecular H-bonding network. Meanwhile, the intramolecular H-bonding network is formed between P(NAGA-co-NBAA) and agars. The sol-gel phase transition of agars at 86 °C generates the molecular entanglement network. Such a double network enables the hydrogel high self-healing efficiency (about 95%), good shape memory ability, and high mechanical strength (1.1 MPa). Additionally, the DN hydrogel is completely crosslinked by multiple hydrogen bonds (H-bonds) and the physical crosslinking of agar without extra potential toxic chemical crosslinker. The DN hydrogels find extensive applications in the biomedical materials due to their excellent biocompatibility.
Asunto(s)
Materiales Biocompatibles/síntesis química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Polimerizacion/efectos de la radiación , Polímeros/síntesis química , Acrilamida/química , Agar/química , Materiales Biocompatibles/química , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/química , Glicina/análogos & derivados , Glicina/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Enlace de Hidrógeno/efectos de la radiación , Transición de Fase , Polímeros/química , Rayos Ultravioleta , Agua/químicaRESUMEN
This study reports an effective method for controlling substance-release sites of hydrogel. Glycidyl methacrylate, which contains two functional groups, namely, double-bond acrylate and epoxide, is photografted on a hydrogel surface through hydrogen abstraction photopolymerization due to the existence of a hydrogen donor, such as an amine, in the hydrogel matrix. The remaining epoxide group crosslinks the polymer chain of polyglycidyl methacrylate. Substance release of hydrogel is changed due to the altered surface texture of hydrogel. Rate and site-controlled substance release are achieved by controlling the thickness and site of surface grafting and the extent of epoxide ring opening. This study may provide a novel method for achieving hydrogel function or modified performance of other biomaterials to meet biological activity requirements.
Asunto(s)
Reactivos de Enlaces Cruzados/química , Sistemas de Liberación de Medicamentos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polímeros/química , Materiales Biocompatibles , Reactivos de Enlaces Cruzados/síntesis química , Liberación de Fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Luz , Polimerizacion/efectos de la radiación , Polímeros/síntesis química , Propiedades de SuperficieRESUMEN
The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.
Asunto(s)
Materiales Biocompatibles/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Dispositivos Laboratorio en un Chip , Microtecnología/instrumentación , Polimerizacion/efectos de la radiación , Andamios del Tejido/química , Animales , Materiales Biocompatibles/síntesis química , Adhesión Celular , Línea Celular , Diseño de Equipo , Hidrogel de Polietilenoglicol-Dimetacrilato/síntesis química , Luz , Ratones , Microtecnología/métodos , SemiconductoresRESUMEN
Synthetic hydrogel materials can recapitulate the natural cell microenvironment; however, it is equally necessary that the gels maintain cell viability and phenotype while permitting reisolation without stress, especially for use in the stem cell field. Here, we describe a family of synthetically accessible, squaramide-based tripodal supramolecular monomers consisting of a flexible tris(2-aminoethyl)amine (TREN) core that self-assemble into supramolecular polymers and eventually into self-recovering hydrogels. Spectroscopic measurements revealed that monomer aggregation is mainly driven by a combination of hydrogen bonding and hydrophobicity. The self-recovering hydrogels were used to encapsulate NIH 3T3 fibroblasts as well as human-induced pluripotent stem cells (hiPSCs) and their derivatives in 3D. The materials reported here proved cytocompatible for these cell types with maintenance of hiPSCs in their undifferentiated state essential for their subsequent expansion or differentiation into a given cell type and potential for facile release by dilution due to their supramolecular nature.