Covalent tethering of photo-responsive superficial layers on hydrogel surfaces for photo-controlled release.
ABSTRACT: The diffusion and transport of substances between a hydrogel and its environment have received tremendous research interest, due to the wide range of applications of hydrogel materials in fields related to drug carriers and drug delivery vehicles. To date, much research has been done to tailor the diffusion and transport of substances through hydrogels, where most efforts were focused on tuning the 3D network properties of the hydrogel including loop size, hydrophobicity of building blocks and the stimuli-responsive properties of backbones. These conventional strategies, however, usually suffer from complicated fabrication procedures and result in a homogeneous increase in hydrophobicity of the hydrogel network, leading to low efficiency control over the diffusion of substances through the hydrogel. Herein, a facile strategy that can functionalize the surfaces of hydrogels, while keeping the interior network unchanged, was reported, and is realized by quaternization reaction confined to the hydrogel/oil interface. Owing to the introduction of the photo-responsive molecule IBSP as a modifier, the surface wettability of the resulting hydrogel can be controlled by light both in air and underwater environments. Consequently, the diffusion rate of a substance through this modified hydrogel can be regulated by light, which brings convenience to the controlled release of hydrogels and other hydrogel-related fields.
Project description:Poly(N-isopropylacrylamide) (PNIPAM) is a widely-studied polymers due to its excellent temperature sensitivity. PNIPAM-MAPOSS hybrid hydrogel, based on the introduction of acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) into the PNIPAM matrix in the presence of polyethylene glycol, was prepared via radical polymerization. The modified hydrogels exhibited a thick, heterogeneous porous structure. PEG was used as a pore-forming agent to adjust the pore size. MAPOSS reduced the swelling ratios of gels, and decreased the LCST, causing the hydrogels to shrink at lower temperatures. However, its hydrophobicity helped to improve the temperature response rate. The incorporation of rigid MAPOSS into the polymer network greatly increased the compressive modulus of the hydrogel. It is worth noting that, by adjusting the amount of MAPOSS and PEG, the hydrogel could have both ideal mechanical properties and swelling behavior. In addition, hydrogel containing 8.33 wt % MAPOSS could achieve stable and sustained drug release. Thus, the prepared PNIPAM-MAPOSS hybrid hydrogel can serve as drug carrier for 5-fluorouracil and may have potential application in other biomedical fields.
Project description:The transport properties of agarose hydrogels enriched by humic acids were studied. Methylene blue, rhodamine 6G and Cu(II) ions were incorporated into hydrogel as diffusion probes, and then their release into water was monitored. Cu(II) ions as well as both the dyes studied in this work have high affinity to humic substances and their interactions strongly affected their diffusion in hydrogels. It was confirmed that humic acids retarded the transport of diffusion probes. Humic acids' enrichment caused the decrease in the values of effective diffusion coefficients due to their complexation with diffusion probes. In general, the diffusion of dyes was more affected by the complexation with humic acids in comparison with Cu(II) ions. The effect of complexation was selective for the particular diffusion probe. The strongest effect was obtained for the diffusion of methylene blue. It was assumed that metal ions interacted preferentially with acidic functional groups. In contrast to Cu(II) ions, dyes can interact with acidic functional groups, and the condensed cyclic structures of the dye probes supported their interactions with the hydrophobic domains of humic substances.
Project description:In this study, we investigated the mineralization capacity and biocompatibility of injectable, dual-gelling hydrogels in a rat cranial defect as a function of hydrogel hydrophobicity from either the copolymerization of a hydrolyzable lactone ring or the hydrogel polymer content. The hydrogel system comprised a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and a polyamidoamine crosslinker. The thermogelling macromer was copolymerized with (TGM/DBA) or without (TGM) a dimethyl-?-butyrolactone acrylate (DBA)-containing lactone ring that modulated the lower critical solution temperature and thus, the hydrogel hydrophobicity, over time. Three hydrogel groups were examined: (1) 15wt.% TGM, (2) 15wt.% TGM/DBA, and (3) 20wt.% TGM/DBA. The hydrogels were implanted within an 8mm critical size rat cranial defect for 4 and 12weeks. Implants were harvested at each timepoint and analyzed for bone formation, hydrogel mineralization and tissue response using microcomputed tomography (microCT). Histology and fibrous capsule scoring showed a light inflammatory response at 4weeks that was mitigated by 12weeks for all groups. MicroCT scoring and bone volume quantification demonstrated a similar bone formation at 4weeks that was significantly increased for the more hydrophobic hydrogel formulations - 15wt.% TGM and 20wt.% TGM/DBA - from 4weeks to 12weeks. A complementary in vitro acellular mineralization study revealed that the hydrogels exhibited calcium binding properties in the presence of serum-containing media, which was modulated by the hydrogel hydrophobicity. The tailored mineralization capacity of these injectable, dual-gelling hydrogels with hydrolysis-dependent hydrophobicity presents an exciting property for their use in bone tissue engineering applications.
Project description:Photopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE.Designing synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an increase in mechanical properties. Nondestructive assays based on mechanical and ultrasonic properties were also investigated using a novel instrument and found to correlate with matrix deposition and evolution. In sum, this study presents a new hydrogel platform combined with nondestructive assessments, which together have potential for in vitro cartilage tissue engineering.
Project description:Hydrogels have been the focus of extensive research due to their potential use in fields including biomedical, pharmaceutical, biosensors, and cosmetics. However, the general weak mechanical properties of hydrogels limit their utility. Here, we generate pristine silk fibroin (SF) hydrogels with excellent mechanical properties via a binary solvent induced conformation transition (BSICT) strategy. In this method, the conformational transition of SF is regulated by moderate binary solvent diffusion and SF/solvent interactions. ?-sheet formation serves as the physical crosslinks that connect disparate protein chains to form continuous 3D hydrogel networks, avoiding complex chemical and/or physical treatments. The Young's modulus of these new BSICT-silk fibroin hydrogels can reach up to 6.5±0.2 MPa, tens to hundreds of times higher than that of conventional hydrogels (0.01-0.1 MPa). These new materials filled the "empty soft materials space" in the elastic modulus/strain Ashby plot. More remarkably, the BSICT-SF hydrogels can be processed into different constructions through different polymer and/or metal based processing techniques, such as molding, laser cutting, and machining. Thus, these new hydrogel systems exhibit potential utility in many biomedical and engineering fields.
Project description:We describe the preparation of hydrogels using highly functionalized poly(oxazoline) based polymeric precursors and cross-linking via UV mediated radical thiol-ene chemistry. Random copolymers were synthesized based on the combination of the more hydrophilic 2-methyl-2-oxazoline or the less hydrophilic monomer 2-ethyl-2-oxazoline with 2-(3-butenyl)-2-oxazoline. These copolymers were functionalized via a post-polymerization technique with thiol or cysteine functionality at the side chain. Hence, hydrogels were obtained, for which the thermo-responsive behavior, network density and correlated properties such as swelling and mechanics, as well as the possibility of electrostatic interaction, can be tuned. Cell culture tests demonstrated good cytocompatibility of the synthesized copolymers and hydrogels. A study with two low molecular weight substances, methylene blue and fluorescein sodium, was performed to investigate how the thermo-responsive behavior or the positive charge incorporated by cysteine could influence the interaction with the compounds. It was found that the interaction with the hydrogel network was strongly influenced by the chemical properties of the dye. A hydrophilic and positively charged hydrogel network was shown to be a promising candidate for the uptake and prolonged release of negatively charged low molecular weight substances.
Project description:Graphene oxide (GO) is increasingly used for controlling mass diffusion in hydrogel-based drug delivery applications. On the macro-scale, the density of GO in the hydrogel is a critical parameter for modulating drug release. Here, we investigate the diffusion of a peptide drug through a network of GO membranes and GO-embedded hydrogels, modelled as porous matrices resembling both laminated and 'house of cards' structures. Our experiments use a therapeutic peptide and show a tunable nonlinear dependence of the peptide concentration upon time. We establish models using numerical simulations with a diffusion equation accounting for the photo-thermal degradation of fluorophores and an effective percolation model to simulate the experimental data. The modelling yields an interpretation of the control of drug diffusion through GO membranes, which is extended to the diffusion of the peptide in GO-embedded agarose hydrogels. Varying the density of micron-sized GO flakes allows for fine control of the drug diffusion. We further show that both GO density and size influence the drug release rate. The ability to tune the density of hydrogel-like GO membranes to control drug release rates has exciting implications to offer guidelines for tailoring drug release rates in hydrogel-based therapeutic delivery applications.
Project description:Hydrogels have received considerable attention due to their potential applications in the fields of drug delivery, tissue engineering, and stimuli-responsive devices. Nonetheless, it is still a great difficulty in designing hydrogels with multifunctional characteristics including excellent antibacterial activity and appropriate mechanical and remarkable sensing properties. In the present study, a novel type of organic-inorganic adhesive is demonstrated, which comprises inorganic matter of amorphous calcium phosphate particles and organic substances of poly(acrylic acid) and chitosan. The hydrogel possesses excellent biocompatible and antibacterial activity, unique viscoelastic properties, high quantity of drug load, and remarkably sensitive pressure sensing, which have potential use as antibacterial biomaterials, artificially intelligent skins, and drug delivery carriers.
Project description:To overcome the slow kinetics of the volume phase transition of stimuli-responsive hydrogels as platforms for soft actuators, thermally responsive comb-type hydrogels were prepared using synthesized poly(N-isopropylacrylamide) macromonomers bearing graft chains. Fast responding light-responsive hydrogels were fabricated by combining a comb-type hydrogel matrix with photothermal magnetite nanoparticles (MNP). The MNPs dispersed in the matrix provide heat to stimulate the volume change of the hydrogel matrix by converting absorbed visible light to thermal energy. In this process, the comb-type hydrogel matrix exhibited a rapid response due to the free, mobile grafted chains. The comb-type hydrogel exhibited significantly enhanced light-induced volume shrinkage and rapid recovery. The comb-type hydrogels containing MNP were successfully used to fabricate a bilayer-type photo-actuator with fast bending motion.
Project description:Current hydrogels used for tissue engineering are limited to a single range of mechanical properties within the replicated tissue construct. We show that repeated in-swelling by a single hydrogel pre-cursor solution into an existing polymerized hydrogel followed by photo-exposure increases hydrogel mechanical properties. The process is demonstrated with a photo-clickable thiol-ene hydrogel using a biocompatible precursor solution of poly(ethylene glycol) dithiol and 8-arm poly(ethylene glycol) functionalized with norbornene. The polymer fraction in the precursor solution was varied by 5, 10, and 20 percent by weight and an off-stoichiometric ratio of thiol?:?ene was used, leaving free enes available for subsequent reaction. Multiple swelling and exposure cycles for the same precursor solution were performed. The compressive modulus increased by a factor between three and ten (formulation dependent), while volume swelling ratio decreased by a factor of two, consistent with increased crosslink density. The modified hydrogels also demonstrate increased toughness by fracturing at compressive forces five times greater than the initial hydrogel. We attribute the increased toughness to subsequent increases in crosslink density created by the repeated photopolymerization of in-swollen macromer. This technique demonstrates the ability to significantly modify hydrogel network properties by exploiting swelling and polymerization processes that can be applied to traditional three-dimensional printing systems to spatially control local mechanical properties.