RESUMO
Stimulating the release of small nanoparticles (NPs) from a larger NP via the application of an exogenous stimulus offers the potential to address the different size requirements for circulation versus penetration that hinder chemotherapeutic drug delivery. Herein, we report a size-switching nanoassembly-based drug delivery system comprised of ultrasmall starch nanoparticles (SNPs, â¼20-50 nm major size fraction) encapsulated in a poly(oligo(ethylene glycol) methyl ether methacrylate) nanogel (POEGMA, â¼150 nm major size fraction) cross-linked via supramolecular PEG/α-cyclodextrin (α-CD) interactions. Upon heating the nanogel using a non-invasive, high-intensity focused ultrasound (HIFU) trigger, the thermoresponsive POEGMA-CD nanoassemblies are locally de-cross-linked, inducing in situ release of the highly penetrative drug-loaded SNPs. HIFU triggering increased the release of nanoassembly-loaded DOX from 17 to 37% after 3 h, a result correlated with significantly more effective tumor killing relative to nanoassemblies in the absence of HIFU or drug alone. Furthermore, 1.5× more total fluorescence was observed inside a tumor spheroid when nanoassemblies prepared with fluorophore-labeled SNPs were triggered with HIFU relative to the absence of HIFU. We anticipate this strategy holds promise for delivering tunable doses of chemotherapeutic drugs both at and within a tumor site using a non-invasive triggering approach.
Assuntos
Doxorrubicina , Polietilenoglicóis , Humanos , Polietilenoglicóis/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Nanogéis/química , Nanopartículas/química , alfa-Ciclodextrinas/química , Sistemas de Liberação de Medicamentos/métodos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Animais , Portadores de Fármacos/química , Linhagem Celular Tumoral , Polietilenoimina/químicaRESUMO
Antimicrobial resistance in agriculture is a global concern and carries huge financial consequences. Despite that, practical solutions for growers that are sustainable, low cost and environmentally friendly have been sparse. This has created opportunities for the agrochemical industry to develop pesticides with novel modes of action. Recently the use of photodynamic inactivation (PDI), classically used in cancer treatments, has been explored in agriculture as an alternative to traditional chemistries, mainly as a promising new approach for the eradication of pesticide resistant strains. However, applications in the field pose unique challenges and call for new methods of evaluation to adequately address issues specific to PDI applications in plants and challenges faced in the field. The aim of this review is to summarize in vitro, ex vivo, and in vivo/in planta experimental strategies and methods used to test and evaluate photodynamic agents as photo-responsive pesticides for applications in agriculture. The review highlights some of the strategies that have been explored to overcome challenges in the field.
Assuntos
Praguicidas , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Agricultura/métodos , Praguicidas/química , Praguicidas/farmacologia , PlantasRESUMO
Multiple biological barriers must be considered in the design of nanomedicines, including prolonged blood circulation, efficient accumulation at the target site, effective penetration into the target tissue, selective uptake of the nanoparticles into target cells, and successful endosomal escape. However, different particle sizes, surface chemistries, and sometimes shapes are required to achieve the desired transport properties at each step of the delivery process. In response, this review highlights recent developments in the design of switchable nanoparticles whose size, surface chemistry, shape, or a combination thereof can be altered as a function of time, a disease-specific microenvironment, and/or via an externally applied stimulus to enable improved optimization of nanoparticle properties in each step of the delivery process. The practical use of such nanoparticles in chemotherapy, bioimaging, photothermal therapy, and other applications is also discussed.
Assuntos
Nanopartículas , Transporte Biológico , Sistemas de Liberação de Medicamentos , Nanomedicina , Nanopartículas/química , Tamanho da PartículaRESUMO
While microgels and nanogels are most commonly used for the delivery of hydrophilic therapeutics, the water-swollen structure, size, deformability, colloidal stability, functionality, and physicochemical tunability of microgels can also offer benefits for addressing many of the barriers of conventional vehicles for the delivery of hydrophobic therapeutics. In this review, we describe approaches for designing microgels with the potential to load and subsequently deliver hydrophobic drugs by creating compartmentalized microgels (e.g., core-shell structures), introducing hydrophobic domains in microgels, leveraging host-guest interactions, and/or applying "smart" environmentally responsive materials with switchable hydrophobicity. In particular, the challenge of promoting hydrophobic drug loading without compromising the inherent advantages of microgels as delivery vehicles and ensuring practically relevant release kinetics from such structures is highlighted, with an eye toward the practical translation of such vehicles to the clinic.
Assuntos
Microgéis , Sistemas de Liberação de Medicamentos , Nanogéis , Preparações Farmacêuticas , ÁguaRESUMO
Dynamic covalent chemistry is an attractive cross-linking strategy for hydrogel bioinks due to its ability to mimic the dynamic interactions that are natively present in the extracellular matrix. However, the inherent challenges in mixing the reactive precursor polymers during printing and the tendency of the soft printed hydrogels to collapse during free-form printing have limited the use of such chemistry in 3D bioprinting cell scaffolds. Herein, we demonstrate 3D printing of hydrazone-cross-linked poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels using the freeform reversible embedding of suspended hydrogels (FRESH) technique coupled with a customized low-cost extrusion bioprinter. The dynamic nature and reversibility of hydrazone cross-links enables reconfiguration of the initially more heterogeneous gel structure to form a more homogeneous internal gel structure, even for more highly cross-linked hydrogels, over a relatively short time (<3 days) while preserving the degradability of the scaffold over longer time frames. POEGMA hydrogels can successfully print NIH/3T3 fibroblasts and human umbilical vein endothelial cells while maintaining high cell viability (>80%) and supporting F-actin-mediated adhesion to the scaffold over a 14-day in vitro incubation period, demonstrating their potential use in practical tissue engineering applications.
Assuntos
Bioimpressão , Humanos , Bioimpressão/métodos , Hidrogéis/química , Hidrazonas , Células Endoteliais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Impressão TridimensionalRESUMO
The emergence of 3D bioprinting has allowed a variety of hydrogel-based "bioinks" to be printed in the presence of cells to create precisely defined cell-loaded 3D scaffolds in a single step for advancing tissue engineering and/or regenerative medicine. While existing bioinks based primarily on ionic cross-linking, photo-cross-linking, or thermogelation have significantly advanced the field, they offer technical limitations in terms of the mechanics, degradation rates, and the cell viabilities achievable with the printed scaffolds, particularly in terms of aiming to match the wide range of mechanics and cellular microenvironments. Click chemistry offers an appealing solution to this challenge given that proper selection of the chemistry can enable precise tuning of both the gelation rate and the degradation rate, both key to successful tissue regeneration; simultaneously, the often bio-orthogonal nature of click chemistry is beneficial to maintain high cell viabilities within the scaffolds. However, to date, relatively few examples of 3D-printed click chemistry hydrogels have been reported, mostly due to the technical challenges of controlling mixing during the printing process to generate high-fidelity prints without clogging the printer. This review aims to showcase existing cross-linking modalities, characterize the advantages and disadvantages of different click chemistries reported, highlight current examples of click chemistry hydrogel bioinks, and discuss the design of mixing strategies to enable effective 3D extrusion bioprinting of click hydrogels.
Assuntos
Bioimpressão , Química Click , Hidrogéis/química , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
Pen-side testing of farm animals for infectious diseases is critical for preventing transmission in herds and providing timely intervention. However, most existing pathogen tests have to be conducted in centralized labs with sample-to-result times of 2-4â days. Herein we introduce a test that uses a dual-electrode electrochemical chip (DEE-Chip) and a barcode-releasing electroactive aptamer for rapid on-farm detection of porcine epidemic diarrhea viruses (PEDv). The sensor exploits inter-electrode spacing reduction and active field mediated transport to accelerate barcode movement from electroactive aptamers to the detection electrode, thus expediting assay operation. The test yielded a clinically relevant limit-of-detection of 6â nM (0.37â µg mL-1 ) in saliva-spiked PEDv samples. Clinical evaluation of this biosensor with 12 porcine saliva samples demonstrated a diagnostic sensitivity of 83 % and specificity of 100 % with a concordance value of 92 % at an analysis time of one hour.
Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Código de Barras de DNA Taxonômico , Diarreia/diagnóstico , Diarreia/veterinária , Vírus da Diarreia Epidêmica Suína/genética , Saliva , Sensibilidade e Especificidade , Suínos , Doenças dos Suínos/diagnósticoRESUMO
Hydrophobic polymer-grafted cellulose nanocrystals (CNCs) were produced via surface-initiated atom-transfer radical polymerization (SI-ATRP) in two different solvents to examine the role of reaction media on the extent of surface modification. Poly(butyl acrylate)-grafted CNCs were synthesized in either dimethylformamide (DMF) (D-PBA-g-CNCs) or toluene (T-PBA-g-CNCs) alongside a free polymer from a sacrificial initiator. The colloidal stability of unmodified CNCs, initiator-modified CNCs, and PBA-g-CNCs in water, DMF, and toluene was evaluated by optical transmittance. The enhanced colloidal stability of initiator-modified CNCs in DMF led to improved accessibility to initiator groups during polymer grafting; D-PBA-g-CNCs had 30 times more grafted chains than T-PBA-g-CNCs, determined by thermogravimetric and elemental analysis. D-PBA-g-CNCs dispersed well in toluene and were hydrophobic with a water contact angle of 124° (for polymer grafts > 13 kDa) compared to 25° for T-PBA-g-CNCs. The cellulose crystal structure was preserved, and individual nanoparticles were retained when grafting was carried out in either solvent. This work highlights that optimizing CNC colloidal stability prior to grafting is more crucial than solvent-polymer compatibility to obtain high graft densities and highly hydrophobic CNCs via SI-ATRP.
Assuntos
Celulose , Nanopartículas , Interações Hidrofóbicas e Hidrofílicas , Polimerização , PolímerosRESUMO
The development of in situ-gelling hydrogels that can enable prolonged protein release is increasingly important due to the emergence of a growing number of protein-based therapeutics. Herein, we describe a high-throughput strategy to fabricate, characterize, and subsequently optimize hydrazone-cross-linked in situ-gelling hydrogels for protein delivery. Hydrogels are fabricated using an automated high-throughput robot to mix a variety of thermoresponsive, nonthermoresponsive, charged, neutral, naturally sourced, and synthetic polymers functionalized with hydrazide or aldehyde groups, generating in situ-gelling hydrogels with well-defined compositions within a 96-well plate. High-throughput characterization strategies are subsequently developed to enable on-plate analysis of hydrogel swelling, mechanics, degradation, transparency, and protein (ovalbumin) release kinetics that yield results consistent with those collected using traditional bulk hydrogel analysis techniques. Dynamic regression and latent variable modeling are then applied to fit performance statistics to the collected data set; subsequently, numerical optimization is used to identify mixtures of precursor polymers that exhibit targeted combinations of minimal burst release, maximum total protein release, minimum release rate, and maximum transparency (the latter of particular relevance for ophthalmic protein delivery applications). Given the rapid throughput of the protocols developed (i.e., 126 hydrogels can be synthesized and screened in quadruplicate within hours), this approach offers particular promise for accelerating the identification of injectable hydrogel compositions relevant for both protein delivery as well as other biomedical applications for which clearly predefined materials properties are required.
Assuntos
Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Proteínas/administração & dosagem , Resinas Acrílicas/química , Quitosana/química , Dextranos/química , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/farmacocinética , Injeções , Cinética , Modelos Teóricos , Ovalbumina/administração & dosagem , Ovalbumina/farmacocinética , Polietilenoglicóis/química , Polímeros/química , Proteínas/farmacocinética , Robótica/métodos , TemperaturaRESUMO
Nanogels and microgels are soft, deformable, and penetrable objects with an internal gel-like structure that is swollen by the dispersing solvent. Their softness and the potential to respond to external stimuli like temperature, pressure, pH, ionic strength, and different analytes make them interesting as soft model systems in fundamental research as well as for a broad range of applications, in particular in the field of biological applications. Recent tremendous developments in their synthesis open access to systems with complex architectures and compositions allowing for tailoring microgels with specific properties. At the same time state-of-the-art theoretical and simulation approaches offer deeper understanding of the behavior and structure of nano- and microgels under external influences and confinement at interfaces or at high volume fractions. Developments in the experimental analysis of nano- and microgels have become particularly important for structural investigations covering a broad range of length scales relevant to the internal structure, the overall size and shape, and interparticle interactions in concentrated samples. Here we provide an overview of the state-of-the-art, recent developments as well as emerging trends in the field of nano- and microgels. The following aspects build the focus of our discussion: tailoring (multi)functionality through synthesis; the role in biological and biomedical applications; the structure and properties as a model system, e.g., for densely packed arrangements in bulk and at interfaces; as well as the theory and computer simulation.
RESUMO
The internal morphology of temperature-responsive degradable poly(N-isopropylacrylamide) (PNIPAM) microgels formed via an aqueous self-assembly process based on hydrazide and aldehyde-functionalized PNIPAM oligomers is investigated. A combination of surface force measurements, small angle neutron scattering (SANS), and ultrasmall angle neutron scattering (USANS) was used to demonstrate that the self-assembled microgels have a homogeneously cross-linked internal structure. This result is surprising given the sequential addition process used to fabricate the microgels, which was expected to result in a densely cross-linked shell-diffuse core structure. The homogeneous internal structure identified is also significantly different than conventional microgels prepared via precipitation polymerization, which typically exhibit a diffuse shell-dense core structure. The homogeneous structure is hypothesized to result from the dynamic nature of the hydrazone cross-linking chemistry used to couple with the assembly conditions chosen that promote polymer interdiffusion. The lack of an internal cross-linking gradient within these degradable and monodisperse microgels is expected to facilitate more consistent drug release over time, improved optical properties, and other potential application benefits.
Assuntos
Resinas Acrílicas/química , Géis/química , Hidrazonas/química , TemperaturaRESUMO
A reactive electrospinning strategy is used to fabricate viable and proliferative cell-loaded nanofibrous hydrogel scaffolds in a single step using an all-aqueous approach. In situ gelling and degradable hydrazone-cross-linked poly(oligo ethylene glycol methacrylate)-based hydrogel nanofibrous networks can be produced directly in the presence of cells to support long-term cell viability, adhesion, and proliferation, in contrast to bulk hydrogels of the same composition. Furthermore, the capacity of the gel nanofibers to retain bound water maintains this high cell viability and proliferative capacity following a freeze/thaw cycle without requiring any cryoprotectant additives, ideal properties for ready-to-use functional tissue patches.
Assuntos
Adesão Celular , Proliferação de Células , Hidrogéis/química , Mioblastos/citologia , Nanofibras/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Sobrevivência Celular , Células Cultivadas , Reagentes de Ligações Cruzadas , Eletricidade , Teste de Materiais , Camundongos , Células NIH 3T3 , PolietilenoglicóisRESUMO
We report a simple method of preparing autonomous and rapid self-adhesive hydrogels and their use as building blocks for additive manufacturing of functional tissue scaffolds. Dynamic cross-linking between 2-aminophenylboronic acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that recover their mechanical integrity within 1 min after cutting or shear under both neutral and acidic pH conditions. Incorporation of this hydrogel in an interpenetrating calcium-alginate network results in an interfacially stiffer but still rapidly self-adhesive hydrogel that can be assembled into hollow perfusion channels by simple contact additive manufacturing within minutes. Such channels withstand fluid perfusion while retaining their dimensions and support endothelial cell growth and proliferation, providing a simple and modular route to produce customized cell scaffolds.
Assuntos
Adesivos/química , Hidrogéis/química , Engenharia Tecidual/métodos , Alicerces Teciduais , Ácidos Borônicos/química , Reagentes de Ligações Cruzadas/química , Células Epiteliais/citologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Álcool de Polivinil/químicaRESUMO
Compositional and structural patterns play a crucial role in the function of many biological tissues. In the present work, for nanofibrillar hydrogels formed by chemically cross-linked cellulose nanocrystals (CNC) and gelatin, we report a microextrusion-based 3D printing method to generate structurally anisotropic hydrogel sheets with CNCs aligned in the direction of extrusion. We prepared hydrogels with a uniform composition, as well as hydrogels with two different types of compositional gradients. In the first type of gradient hydrogel, the composition of the sheet varied parallel to the direction of CNC alignment. In the second hydrogel type, the composition of the sheet changed orthogonally to the direction of CNC alignment. The hydrogels exhibited gradients in structure, mechanical properties, and permeability, all governed by the compositional patterns, as well as cytocompatibility. These hydrogels have promising applications for both fundamental research and for tissue engineering and regenerative medicine.
Assuntos
Celulose/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanofibras/química , Engenharia Tecidual , Anisotropia , Celulose/síntese química , Gelatina/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Nanopartículas/química , Medicina RegenerativaRESUMO
While injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.
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Highly monodisperse and hydrolytically degradable thermoresponsive microgels on the tens-to-hundreds of micron size scale have been fabricated based on simultaneous on-chip mixing and emulsification of aldehyde and hydrazide-functionalized poly(N-isopropylacrylamide) precursor polymers. The microfluidic chip can run for extended periods without upstream gelation and can produce monodisperse (<10% particle size variability) microgels on the size range of â¼30-90 µm, with size tunable according to the flow rate of the oil continuous phase. Fluorescence analysis indicates a uniform distribution of each reactive pre-polymer inside the microgels while micromechanical testing suggests that smaller microfluidic-produced microgels exhibit significantly higher compressive moduli compared to bulk hydrogels of the same composition, an effect we attribute to improved mixing (and thus crosslinking) of the precursor polymer solutions within the microfluidic device. The microgels retain the reversible volume phase transition behavior of conventional microgels but can be hydrolytically degraded back into their oligomeric precursor polymer fragments, offering potential for microgel clearance following use in vivo.
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Cellulose nanocrystals (CNCs) are emerging nanomaterials that form chiral nematic liquid crystals above a critical concentration (C*) and additionally orient within electromagnetic fields. The control over CNC alignment is significant for materials processing and end use; to date, magnetic alignment has been demonstrated using only strong fields over extended or arbitrary time scales. This work investigates the effects of comparatively weak magnetic fields (0-1.2 T) and CNC concentration (1.65-8.25 wt %) on the kinetics and degree of CNC ordering using small-angle X-ray scattering. Interparticle spacing, correlation length, and orientation order parameters (η and S) increased with time and field strength following a sigmoidal profile. In a 1.2 T magnetic field for CNC suspensions above C*, partial alignment occurred in under 2 min followed by slower cooperative ordering to achieve nearly perfect alignment in under 200 min (S = -0.499 where S = -0.5 indicates perfect antialignment). At 0.56 T, nearly perfect alignment was also achieved, yet the ordering was 36% slower. Outside of a magnetic field, the order parameter plateaued at 52% alignment (S = -0.26) after 5 h, showcasing the drastic effects of relatively weak magnetic fields on CNC alignment. For suspensions below C*, no magnetic alignment was detected.
RESUMO
While injectable hydrogels have several advantages in the context of biomedical use, their generally weak mechanical properties often limit their applications. Herein, we describe in situ-gelling nanocomposite hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA) and rigid rod-like cellulose nanocrystals (CNCs) that can overcome this challenge. By physically incorporating CNCs into hydrazone cross-linked POEGMA hydrogels, macroscopic properties including gelation rate, swelling kinetics, mechanical properties, and hydrogel stability can be readily tailored. Strong adsorption of aldehyde- and hydrazide-modified POEGMA precursor polymers onto the surface of CNCs promotes uniform dispersion of CNCs within the hydrogel, imparts physical cross-links throughout the network, and significantly improves mechanical strength overall, as demonstrated by quartz crystal microbalance gravimetry and rheometry. When POEGMA hydrogels containing mixtures of long and short ethylene oxide side chain precursor polymers were prepared, transmission electron microscopy reveals that phase segregation occurs with CNCs hypothesized to preferentially locate within the stronger adsorbing short side chain polymer domains. Incorporating as little as 5 wt % CNCs results in dramatic enhancements in mechanical properties (up to 35-fold increases in storage modulus) coupled with faster gelation rates, decreased swelling ratios, and increased stability versus hydrolysis. Furthermore, cell viability can be maintained within 3D culture using these hydrogels independent of the CNC content. These properties collectively make POEGMA-CNC nanocomposite hydrogels of potential interest for various biomedical applications including tissue engineering scaffolds for stiffer tissues or platforms for cell growth.
Assuntos
Celulose/química , Hidrogéis/química , Metacrilatos/química , Nanocompostos/química , Nanopartículas/química , Polietilenoglicóis/química , Células 3T3 , Animais , Reagentes de Ligações Cruzadas/química , Módulo de Elasticidade , Óxido de Etileno/química , Camundongos , Estresse Mecânico , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
A series of poly(ethylene glycol) (PEG) hydrogels was synthesized using strain-promoted alkyne-azide cycloaddition (SPAAC) between PEG chains terminated with either aza-dibenzocyclooctynes or azide functionalities. The gelation process was found to occur rapidly upon mixing the two components in aqueous solution without the need for external stimuli or catalysts, making the system a candidate for use as an injectable hydrogel. The mechanical and rheological properties of these hydrogels were found to be tunable by varying the polymer molecular weight and the number of cross-linking groups per chain. The gelation times of these hydrogels ranged from 10 to 60 s at room temperature. The mass-based swelling ratios varied from 45 to 76 at maximum swelling (relative to the dry state), while the weight percent of polymer in these hydrogels ranged from 1.31 to 2.05%, demonstrating the variations in amount of polymer required to maintain the structural integrity of the gel. Each hydrogel degraded at a different rate in PBS at pH = 7.4, with degradation times ranging from 1 to 35 days. By changing the composition of the two starting components, it was found that the Young's modulus of each hydrogel could be varied from 1 to 18 kPa. Hydrogel incubation with bovine serum albumin showed minimal protein adsorption. Finally, a cell cytotoxicity study of the precursor polymers with 3T3 fibroblasts demonstrated that the azide- and strained alkyne-functionalized PEGs are noncytotoxic.
Assuntos
Alcinos/química , Azidas/química , Hidrogéis/química , Polietilenoglicóis/química , Células 3T3 , Adsorção , Animais , Reagentes de Ligações Cruzadas/química , Módulo de Elasticidade , Fibroblastos/efeitos dos fármacos , Hidrogéis/efeitos adversos , Hidrogéis/síntese química , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Reologia , Soroalbumina Bovina/químicaRESUMO
Hydrogels have been widely explored for biomedical applications, with injectable hydrogels being of particular interest for their ability to precisely deliver drugs and cells to targets. Although these hydrogels have demonstrated satisfactory properties in many cases, challenges still remain for commercialization. In this paper, we describe a simple injectable hydrogel based on poly(ethylene glycol) (PEG) and a vitamin E (Ve) methacrylate copolymer prepared via simple free radical polymerization and delivered in a solution of low molecular weight PEG and Ve as the solvent instead of water. The hydrogel formed immediately in an aqueous environment with a controllable gelation time. The driving force for gelation is attributed to the self-assembly of hydrophobic Ve residues upon exposure to water to form a physically cross-linked polymer network via polymer chain rearrangement and subsequent phase separation, a spontaneous process with water uptake. The hydrogels can be customized to give the desired water content, mechanical strength, and drug release kinetics simply by formulating the PEGMA-co-Ve polymer with an appropriate solvent mixture or by varying the molecular weight of the polymer. The hydrogels exhibited no significant cytotoxicity in vitro using fibroblasts and good tissue compatibility in the eye and when injected subcutaneously. These polymers thus have the potential to be used in a variety of applications where injection of a drug or cell containing depot would be desirable.