Showing papers on "Self-healing hydrogels published in 2003"
TL;DR: Hydrogels are an appealing scaffold material because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner.
4,573 citations
3,307 citations
TL;DR: Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 μg per defect.
Abstract: Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (kcat and Km) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 μg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.
1,376 citations
TL;DR: Rat subcutaneous implants of the novel GMHA hydrogels showed good biocompatibility, little inflammatory response, and similar levels of vascularization at the implant edge compared with those of fibrin positive controls, and are suitable for modification with adhesive peptide sequences and use in a variety of wound-healing applications.
Abstract: Ideally, rationally designed tissue engineering scaffolds promote natural wound healing and regeneration. Therefore, we sought to synthesize a biomimetic hydrogel specifically designed to promote tissue repair and chose hyaluronic acid (HA; also called hyaluronan) as our initial material. Hyaluronic acid is a naturally occurring polymer associated with various cellular processes involved in wound healing, such as angiogenesis. Hyaluronic acid also presents unique advantages: it is easy to produce and modify, hydrophilic and nonadhesive, and naturally biodegradable. We prepared a range of glycidyl methacrylate-HA (GMHA) conjugates, which were subsequently photopolymerized to form crosslinked GMHA hydrogels. A range of hydrogel degradation rates was achieved as well as a corresponding, modest range of material properties (e.g., swelling, mesh size). Increased amounts of conjugated methacrylate groups corresponded with increased crosslink densities and decreased degradation rates and yet had an insignificant effect on human aortic endothelial cell cytocompatibility and proliferation. Rat subcutaneous implants of the GMHA hydrogels showed good biocompatibility, little inflammatory response, and similar levels of vascularization at the implant edge compared with those of fibrin positive controls. Therefore, these novel GMHA hydrogels are suitable for modification with adhesive peptide sequences (e.g., RGD) and use in a variety of wound-healing applications.
770 citations
TL;DR: The synthesis of novel hybrid hydrogels by stepwise copolymerization of multiarm vinyl sulfone-terminated poly(ethylene glycol) macromers and alpha-omega cysteine oligopeptides via Michael-type additions is described, and structure and properties are very sensitive to the preparation state including stoichiometry and precursor concentration and lesssensitive to the pH during cross-linking.
721 citations
TL;DR: Electrically-responsive hydrogels, response of gels to an electric field and electrically-stimulated drug release are discussed.
575 citations
TL;DR: The chiral stationary phase for high-performance liquid chromatography shows good chiral recognition ability and high uniformity in both the liquid phase and the solid phase.
Abstract: Keywords: Biomaterials ; Cells ; Hydrogels ; Peptides ; Tissue Engineering Reference UPLUT-ARTICLE-2003-003doi:10.1002/adma.200304621 Record created on 2008-05-26, modified on 2017-05-12
535 citations
TL;DR: In this article, a 3D template of a colloidal template has been used to template the growth of meso-structured semiconductors, metals, polymers, and polymers.
Abstract: Synthesis of three-dimensional (3D) functional structures through colloidal templating is a topic of growing interest in materials chemistry, especially in the fields of optics, chemical sensing, and microfluidics. Colloidal crystals with 3D transla-tional order can be formed from suspension by self-assembly methods such as patterned sedimentation, [1] controlled evaporation , [2,3] sonication, [4] and other methods. [5] These colloidal crystals have been utilized to template the growth of meso-structured semiconductors, [3,6,7] metals, [8±10] and polymers. Because the colloidal template has a characteristic spacing of the order of hundreds of nanometers, the resulting structure interacts strongly with visible and infrared light, leading to optical diffraction that follows Bragg's law:
511 citations
TL;DR: In this paper, the effects of the composition, such as the amounts of clay, polymer, and water content in DMAA-NC gels, on the tensile mechanical properties were investigated in detail.
Abstract: Nanocomposite type hydrogels (DMAA-NC gels) consisting of organic (polymer)/inorganic (clay) networks were prepared by in-situ free-radical polymerization of N,N-dimethylacrylamide (DMAA) in the presence of inorganic clay in aqueous solution. The composition of the NC gels could be controlled directly by altering the composition of the initial reaction mixture. The resulting DMAA-NC gels were mostly uniform and transparent, irrespective of their clay and polymer contents. From DSC, X-ray, TEM, and tensile mechanical measurements, the network structure was established. Contrary to conventional chemically cross-linked hydrogels (DMAA-OR gels) prepared by chemical cross-linking with a difunctional monomer, DMAA-NC gels exhibit superb mechanical properties with astonishingly large elongations at break, near to or greater than 1500%. The effects of the composition, such as the amounts of clay, polymer, and water content in DMAA-NC gels, on the tensile mechanical properties were investigated in detail. With inc...
466 citations
TL;DR: The important role of hydrogel degradation in controlling and influencing the deposition and distribution of extracellular matrix molecules was demonstrated and quantified.
Abstract: In developing a scaffold to support new tissue growth, the degradation rate and mass loss profiles of the scaffold are important design parameters. In this study, hydrogels were prepared by copolymerizing a degradable macromer, poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) endcapped with acrylate groups (PEG-LA-DA) with a nondegradable macromer, poly(ethylene glycol) dimethacrylate (PEGDM). The resulting hydrogels exhibited a range of degradation behavior and mass loss profiles. Chondrocytes were photoencapsulated in gels formulated with 50:50, 25:75, and 15:85 (mol % PEGDM: mol % PEG-LA-DA) and cultured for 6 weeks in vitro. The neocartilaginous tissue formed was examined biochemically and histologically. After 6 weeks, the DNA content in gels with 75 and 85% degradable crosslinks was nearly twice that of the DNA content in the 50% gels. The total collagen content was significantly higher in the 85% gel [2.4 +/- 0.8% wet weight (ww)] compared to the 50% gel (0.22 +/- 0.29% ww). In examining the neocartilaginous tissue with immunohistochemistry, type II collagen was localized in the pericellular region in the 50% gel; however, when increased degradation was incorporated into the gel, type II collagen was found throughout the neotissue. In summary, the important role of hydrogel degradation in controlling and influencing the deposition and distribution of extracellular matrix molecules was demonstrated and quantified.
461 citations
TL;DR: Hyaluronic acid was derivatized with methacrylic esters used for the preparation of hydrogels via photopolymerization and the incorporation of RGD peptides allowed modulation of the HA properties from cell non-adhesive to adhesive.
TL;DR: N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions that respond to a ligand-receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition.
Abstract: N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions. These hydrogels respond to a ligand−receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition.
TL;DR: A small de novo designed peptide (MAX3) is described that exhibits complete thermoreversible self-assembly into a hydrogel network and can be tuned by altering the hydrophobicity of the peptides.
Abstract: A small de novo designed peptide (MAX3) is described that exhibits complete thermoreversible self-assembly into a hydrogel network. Importantly, a prerequisite to hydrogelation is that the peptide ...
TL;DR: The ability to encapsulate MSCs to form cartilage-like tissue in vitro in a photopolymerizing hydrogel may be useful for minimally invasive implantation, MSC differentiation, and engineering of composite tissue structures with multiple cellular phenotypes.
Abstract: Mesenchymal stem cells (MSCs) from skeletally mature goats were encapsulated in a photopolymerizing poly(ethylene glycol)-based hydrogel and cultured with or without transforming growth factor beta1 (TGF) to study the potential for chondrogenesis in a hydrogel scaffold system amenable to minimally invasive implantation. Chondrogenic differentiation was evaluated by histological, biochemical, and RNA analyses for the expression of cartilage extracellular matrix components. The two control groups studied were MSCs cultured in monolayer and MSCs encapsulated in the hydrogel and cultured for 6 weeks in chondrogenic medium without TGF-beta1 (6wk-TGF). The three experimental time points for encapsulated cells studied were 0 days (0d), 3 weeks, and 6 weeks in chondrogenic medium with TGF-beta1 at 10 ng/ml (3wk+TGF and 6wk+TGF). MSCs proliferated in the hydrogels with TGF-beta1. Glycosaminoglycan (GAG) and total collagen content of the hydrogels increased to 3.5% dry weight and 5.0% dry weight, respectively, in 6wk+TGF constructs. Immunohistochemistry revealed the presence of aggrecan, link protein, and type II collagen. Upregulation of aggrecan and type II collagen gene expression compared with monolayer MSCs was demonstrated. Type I collagen gene expression decreased from 3 to 6 weeks in the presence of TGF-beta1. 6wk-TGF hydrogels produced no GAG and only moderate amounts of collagen. However, immunohistochemistry and RT-PCR demonstrated a small amount of spontaneous differentiation in this control group. This study demonstrates the ability to encapsulate MSCs to form cartilage-like tissue in vitro in a photopolymerizing hydrogel. This system may be useful for minimally invasive implantation, MSC differentiation, and engineering of composite tissue structures with multiple cellular phenotypes.
TL;DR: In this paper, a fast-swelling highly porous superabsorbent hydrogels were synthesized through a rapid solution polymerization of concentrated partially neutralized acrylic acid under normal atmospheric conditions.
TL;DR: Results demonstrate that disulfide-crosslinked HA-gelatin hydrogels, a new type of covalent synthetic ECM, constitute biocompatible and biodegradable substrata for cell culture in vitro.
TL;DR: This work hypothesized that the high viscosity of pre-gelled solutions typically used in these applications may decrease cell viability due to the high shear forces required to mix cells with these solutions, and proposed reducing the molecular weight of the polymer used to form the gel, while maintaining its gel-forming ability.
TL;DR: Alginate hydrogels with a range of degradation rates by gamma-irradiating high-molecular-weight alginate yield polymers of various molecular weights and structures indicate that biomaterial degradability is a critical design criterion for achieving optimal tissue regeneration with cell transplantation.
Abstract: It is widely assumed that coupling the degradation rate of polymers used as cell transplantation carriers to the growth rate of the developing tissue will improve its quantity or quality. To test this hypothesis, we developed alginate hydrogels with a range of degradation rates by gamma-irradiating high-molecular-weight alginate to yield polymers of various molecular weights and structures. Decreasing the size of the polymer chains increased the degradation rate in vivo, as measured by implant retrieval rates, masses, and elastic moduli. Rapidly and slowly degrading alginates, covalently modified with RGD-containing peptides to control cell behavior, were then used to investigate the effect of biodegradation rate on bone tissue development in vivo. The more rapidly degrading gels led to dramatic increases in the extent and quality of bone formation. These results indicate that biomaterial degradability is a critical design criterion for achieving optimal tissue regeneration with cell transplantation.
TL;DR: It was found that high purity and high G-type alginate retained 27% of its initial strength after 12 days in culture and that comparable levels of proliferation were observed on this material and tissue culture plastic.
TL;DR: Apply in concert, dynamic deformational loading and TGF-beta1 or IGF-I increased the aggregate modulus of engineered constructs by 277 or 245%, respectively, an increase greater than the sum of either stimulus applied alone.
Abstract: It has previously been demonstrated that dynamic deformational loading of chondrocyte-seeded agarose hydrogels over the course of 1 month can increase construct mechanical and biochemical propertie...
TL;DR: The controlled release technology of BMP-2 for a certain time period was essential to induce the potential activity for bone formation as well as to develop a carrier for the controlled release of bone morphogenetic protein-2 suitable for enhancement of the bone regeneration activity.
Patent•
22 Apr 2003
TL;DR: In this article, the authors presented a method to obtain improved elasticity and mechanical strength properties by subjecting a hydrogel formulation containing a strengthening agent to chemical or physical crosslinking conditions subsequent to initial gel formation.
Abstract: Hydrogels having improved elasticity and mechanical strength properties are obtained by subjecting a hydrogel formulation containing a strengthening agent to chemical or physical crosslinking conditions subsequent to initial gel formation. Superporous hydrogels having improved elasticity and mechanical strength properties are similarly obtained whenever the hydrogel formulation is provided with a foaming agent. Interpenetrating networks of polymer chains comprised of primary polymer(s) and strengthening polymer(s) are thereby formed. The primary polymer affords capillary-based water sorption properties while the strengthening polymer imparts significantly enhanced mechanical strength and elasticity to the hydrogel or superporous hydrogel. Suitable strengthening agents can be natural or synthetic polymers, polyelectrolytes, or neutral, hydrophilic polymers.
TL;DR: Results suggest that peptide-cross-linked P(NIPAAm-co-AAc) hydrogels can be tailored to create environmentally-responsive artificial extracellular matrixes that are degraded by proteases.
TL;DR: Histological examination has demonstrated an advanced granulation tissue formation, capillary formation and epithelialization in wounds treated with FGF-2-incorporated chitosan hydrogels in db/db mice.
TL;DR: In this paper, degradable hydrogels were used to tune the degradation profiles of polymer cell carriers to match cell and tissue growth, which is an important design parameter for (cartilage) tissue engineering.
TL;DR: In this article, the authors evaluated the potential use of thermoresponsive hydrogels based on N-isopropylacrylamide as actuators in microfluidic and lab-on-a-chip devices.
TL;DR: A new class of injectable and bioabsorbable supramolecular hydrogels formed from poly(ethylene oxide)s (PEOs) and alpha-cyclodextrin (alpha-CD) for controlled drug delivery based on physical crosslinking induced by supramolescular self-assembling with no chemical crossl linking reagent involved is described.
Abstract: Polymeric hydrogels long have attracted interest for biomaterials applications because of their generally favorable biocompatibility. High in water content, they are particularly attractive for delivery of delicate bioactive agents, such as proteins. However, because they require covalent crosslinking for gelation, many hydrogels can be applied only as implantables, and incorporation of drugs by sorption may be time-consuming and limiting with regard to the loading level. Therefore a delivery formulation where gelation and drug loading can be achieved simultaneously, taking place in an aqueous environment and without covalent crosslinking, would be attractive. Herein is described a new class of injectable and bioabsorbable supramolecular hydrogels formed from poly(ethylene oxide)s (PEOs) and α-cyclodextrin (α-CD) for controlled drug delivery. The hydrogel formation is based on physical crosslinking induced by supramolecular self-assembling with no chemical crosslinking reagent involved. The supramolecular structure of the hydrogels was confirmed with wide-angle X-ray diffraction studies. The gelation kinetics was found to be dependent on the concentrations of the polymer and α-CD as well as on the molecular weight of the PEO used. The rheologic studies of the hydrogels showed that the hydrogels were thixotropic and reversible and that they could be injected through fine needles. The components of the supramolecular hydrogels potentially are biocompatible and nontoxic. Drugs can be encapsulated directly into the hydrogels in situ at room temperature without any contact with organic solvents. The supramolecular hydrogels were evaluated in terms of their in vitro release kinetics. The rate-controlling mechanism of macromolecular drug release might be the erosion of the hydrogels. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 196–202, 2003
TL;DR: In this paper, the effects of preparation parameters such as PVP content in the hydrogel and irradiation dose on the swelling behavior of the PVP/AAc copolymer hydrogels were studied.
TL;DR: Swelling experiments indicate hydrogel mass decreases by 80-90% gradually over an approximate 50 degrees C temperature range, and changes in gel stiffness and loss angle with cross-linking formulation suggest a low-temperature gel structure that is nearly completely elastic, and a high-tem temperature gel structure, where ELP chains are contracted and force is transmitted through chemical cross-links as well as frictional contact between polypeptide chains.
TL;DR: In this article, the authors used the exponential relation Mt/M∞ = ktn (where Mt is the mass of water absorbed at time t and M∞ is the weight of water at equilibrium) to calculate the exponent (n) describing the Fickian or non-Fickian behavior of swelling polymer networks.
Abstract: There have been many attempts to use anionic hydrogels as oral protein delivery carriers because of their pH-responsive swelling behavior. The dynamic swelling behavior of poly(methacrylic acid-co-methacryloxyethyl glucoside) and poly(methacrylic acid-g-ethylene glycol) hydrogels was investigated to determine the mechanism of water transport through these anionic hydrogels. The exponential relation Mt/M∞ = ktn (where Mt is the mass of water absorbed at time t and M∞ is the mass of water absorbed at equilibrium) was used to calculate the exponent (n) describing the Fickian or non-Fickian behavior of swelling polymer networks. The mechanism of water transport through these gels was significantly affected by the pH of the swelling medium. The mechanism of water transport became more relaxation-controlled in a swelling medium of pH 7.0, which was higher than pKa of the gels. The experimental results of the time-dependent swelling behaviors of the gels were analyzed with several mathematical models. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1606–1613, 2003