Showing papers on "Self-healing hydrogels published in 1998"
TL;DR: The mild conditions under which gel formation can be controlled suggest that artificial proteins that undergo reversible gelation in response to changes in pH or temperature have potential in bioengineering applications requiring encapsulation or controlled release of molecular and cellular species.
Abstract: Recombinant DNA methods were used to create artificial proteins that undergo reversible gelation in response to changes in pH or temperature. The proteins consist of terminal leucine zipper domains flanking a central, flexible, water-soluble polyelectrolyte segment. Formation of coiled-coil aggregates of the terminal domains in near-neutral aqueous solutions triggers formation of a three-dimensional polymer network, with the polyelectrolyte segment retaining solvent and preventing precipitation of the chain. Dissociation of the coiled-coil aggregates through elevation of pH or temperature causes dissolution of the gel and a return to the viscous behavior that is characteristic of polymer solutions. The mild conditions under which gel formation can be controlled (near-neutral pH and near-ambient temperature) suggest that these materials have potential in bioengineering applications requiring encapsulation or controlled release of molecular and cellular species.
1,028 citations
TL;DR: Photopolymerized crosslinked networks of poly(ethylene glycol; PEG) diacrylate (MW 8000) were derivitized throughout their bulk with Arg-Gly-Asp (RGD)-containing peptide sequences to promote spreading of human foreskin fibroblasts over 24 h.
Abstract: Photopolymerized crosslinked networks of poly(ethylene glycol; PEG) diacrylate (MW 8000) were derivitized throughout their bulk with Arg-Gly-Asp (RGD)-containing peptide sequences. Incorporation was achieved by functionalizing the amine terminus of the peptide with an acrylate moiety, thereby enabling the adhesion peptide to copolymerize rapidly with the PEG diacrylate upon photoinitiation. PEG diacrylate hydrogels derivitized with RGD peptide at surface concentrations ranging from 0.001 to 1 pmol/cm2 were studied in vitro for their ability to promote spreading of human foreskin fibroblasts over 24 h. Hydrogels not derivitized with peptides were poor substrates for adhesion, permitting spreading of only 5% of the seeded cells. When immobilized with no spacer arm, both RGD and RDG (inactive control) supported spreading of approximately 50% and approximately 15% of cells at 1 and 0.1 pmol/cm2 surface concentrations respectively; lower concentrations did not promote spreading. When a MW 3400 PEG spacer arm was incorporated between the hydrogel and the peptide linkage, incorporation of 1 pmol/cm2 RGD promoted 70% spreading whereas RDG at the same concentration did not promote spreading. In addition, when cells were seeded in serum-free medium, only RGD peptides incorporated with a spacer arm were able to promote spreading. Thus peptide incorporated into PEG 8000 diacrylate hydrogels without a spacer arm nonspecifically mediated cell spreading whereas incorporation via a MW 3400 PEG spacer arm was required to permit cell spreading to be specifically mediated.
978 citations
Patent•
14 Aug 1998
TL;DR: In this article, a combination of physical and chemical crosslinking processes are used to stabilize the hydrogel-forming precursor solutions at a deposition site for a period of time sufficient for more resilient chemical crosslinks to form.
Abstract: Compositions and methods for forming hydrogels in situ through a combination of physical and chemical crosslinking processes are provided in which physical crosslinking is mediated by one or more natural or synthetic components that stabilize the a hydrogel-forming precursor solutions at a deposition site for a period of time sufficient for more resilient chemical crosslinks to form. Methods of using such hydrogels as tissue coatings to prevent postsurgical adhesion formation, as tissue augmentation or luminal occlusion aids, as matrices for carrying cells, drugs or other bioactive species, as tissue sealants or adhesives, and as medical device coatings also are provided.
857 citations
TL;DR: In this paper, various mathematical models derived to explain and predict solute diffusion in hydrogels are reviewed and tested against literature data, and it was determined that a scaling hydrodynamic model provided the best explanation for solutes diffusion.
Abstract: Solute diffusion in hydrogels is important in many biotechnology fields. Solute behavior in hydrogels has been explained in terms of reduction in hydrogel free volume, enhanced hydrodynamic drag on the solute, increased path length due to obstruction, and a combination of hydrodynamic drag and obstruction effects. In this article the various mathematical models derived to explain and predict solute diffusion in hydrogels are reviewed and tested against literature data. These models can be divided into those applicable to hydrogels composed of flexible polymer chains (i.e., homogeneous hydrogels) and those composed of rigid polymer chains (i.e., heterogeneous hydrogels). For homogeneous hydrogels it was determined that a scaling hydrodynamic model provided the best explanation for solute diffusion, while for heterogeneous hydrogels obstruction models were more consistent with the experimental data. Both the scaling hydrodynamic model and the most appropriate obstruction model contain undefined parameters w...
838 citations
TL;DR: Experimental data show that sustained release of growth factor from the gelatin hydrogels is very effective in exerting the biological functions of the growth factor.
787 citations
TL;DR: Hydrogel membranes formed by interfacially photopolymerizing poly(ethylene glycol) diacrylate precursor solution were prepared from PEG diacylate of molecular weights ranging from 2000 to 20000 with concentrations ranging from 10% to 30% w/w and were impermeable to proteins with a size equal to or larger than myoglobin.
621 citations
TL;DR: Methods for polyhydrazide synthesis, for prodrug preparation, for hydrogel crosslinking, and for monitoring biodegradation are described.
440 citations
TL;DR: In this paper, the deswelling response on raising the temperature of this gel above the gel phase transition temperature (TP) takes place within 10 min, whereas a conventionally cross-linked PIPAAm gel of the same dimensions requires 1 month.
Abstract: Poly(ethylene oxide) (PEO) chains are introduced as graft chains maintaining freely mobile ends in thermo-responsive cross-linked poly(N-isopropylacrylamide) (PIPAAm) hydrogels by copolymerization of IPAAm with α-acryloyl-ω-methoxy-PEO. The deswelling response on raising the temperature of this gel above the gel phase transition temperature (TP) takes place within 10 min, whereas a conventionally cross-linked PIPAAm gel of the same dimensions requires 1 month for deswelling. This difference is due to the formation of water release channels within the skin layer by the hydrophilic PEO graft chains. The rapid deswelling of the grafted gel is compared with the deswelling changes of random copolymer gels composed of IPAAm and hydrophilic acrylic acid (AAc), which also accelerates gel deswelling. Deswelling is fastest in copolymers containing 1.3 wt % AAc and in grafted gels containing 13 wt % PEO. These results were interpreted as reflecting the gel structure.
327 citations
TL;DR: This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immuno-competent porcine animal model to determine the feasibility of engineering tissue generated from different cell-polymer constructs prior to human application.
Abstract: New cartilage formation has been successfully achieved by a technology referred to as tissue engineering. Polymers and hydrogels such as poly(glycolic acid), calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used as cell carriers to regenerate cartilage in the nude mouse model. The next step toward human applications of engineered cartilage is to demonstrate their potential in immunocompetent animal models. This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immuno-competent porcine animal model. Auricular cartilage was obtained from pigs. Chondrocytes were isolated and seeded onto fiber based poly(glycolic acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at constant concentrations. Chondrocyte-polymer constructs were either implanted (PGA) or injected (calcium alginate and pluronic) as autologous implants subcutaneously into the pigs from which the cells had been isolate...
300 citations
TL;DR: In this article, the authors used sputter deposition to imprint the surface of an N-isopropylacrylamide (NIPA) gel with a square array of gold thin films.
Abstract: The polymer gels called hydrogels may be induced to swell or shrink (taking up or expelling water between the crosslinked polymer chains) in response to a variety of environmental stimuli, such as changes in pH or temperature, or the presence of a specific chemical substrate1. These gels are being explored for several technological applications, particularly as biomedical materials2. When hydrogels swell or shrink, complex patterns may be generated on their surfaces3,4,5,6,7. Here we report the synthesis and controlled modulation of engineered surface patterns on environmentally responsive hydrogels. We modify the character of a gel surface by selectively depositing another material using a mask. For example, we use sputter deposition to imprint the surface of an N-isopropylacrylamide (NIPA) gel with a square array of gold thin films. The periodicity of the array can be continuously varied as a function of temperature or electric field (which alter the gel's volume), and so such an array might serve as an optical grating for sensor applications. We also deposit small areas of an NIPA gel onthe surface of an acrylamide gel; the patterned area can be rendered invisible reversibly by switching the temperature above or below the lower critical solution temperature of the NIPA gel. We anticipate that these surface patterning techniques may find applications in display and sensor technology.
280 citations
TL;DR: The systematic engineering of multi-component, environmentally responsive hydrogel microspheres, coated with a lipid bilayer to mimic more closely the natural secretory granule are described.
Abstract: Secretory cells contain submicroscopic granules composed of a polyanionic polymer network that is collapsed owing to the presence of hydronium ions and weak base cations. The network is encapsulated within a lipid membrane, and functions as a vehicle for the osmotically inert storage of a variety of granule-bound endogenous mediator species, such as histamine, serotonin and proteases. These species are excreted from the granule and thence from the cell in response to external biochemical signals. Hydrogels that swell and shrink in response to external stimuli might serve as synthetic analogues of secretory granules. Here we describe the systematic engineering of multi-component, environmentally responsive hydrogel microspheres, coated with a lipid bilayer to mimic more closely the natural secretory granule. These microspheres exhibit pH- and ion-dependent volume phase transitions and ion-sensitive exchange of bound cations when the encapsulating lipid membrane is porated. We stimulated poration electrically in individual microgel particles immobilized and manipulated with a micropipette. This system could find use for the triggered release of encapsulated drugs in the body.
TL;DR: Subcutaneous implantation studies in mice showed that in vivo the hydrogel was biocompatible since the foreign body reaction seen around the implanted hydrogels samples was moderate and became minimal upon increasing implantation time.
TL;DR: In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h and follows a diffusion-controlled mechanism, and the number of freezing-thawing cycle and release temperature both influence BSArelease rate considerably.
Patent•
15 Apr 1998
TL;DR: In this article, a vehicle for effecting drug delivery from a solid substrate is proposed, which is particularly useful in the treatment and prevention of biofilm mediated infection often associated with the use of in-dwelling medical devices.
Abstract: The present invention is directed to a vehicle for effecting drug delivery from a solid substrate. Hydrogels loaded with liposomal therapeutic agents such as antibiotics are covalently bonded to the surface of substrates such as in-dwelling medical devices, such as implants, catheters, and the like. The present invention is particularly useful in the treatment and prevention of biofilm mediated infection often associated with the use of in-dwelling medical devices.
TL;DR: It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone in marked contrast to free bFGF of the same dose.
Patent•
14 Aug 1998
TL;DR: In this article, a water-insoluble copolymer with a bioresorbable region, a hydrophilic region and at least two crosslinkable functional groups per polymer chain is described.
Abstract: Cross-linked compositions formed from a water-insoluble copolymer are disclosed. These compositions are copolymers having a bioresorbable region, a hydrophilic region and at least two crosslinkable functional groups per polymer chain. These compositions are able to form hydrogels in aqueous environments when cross-linked. These hydrogels are good sealants for implantable prostheses when in contact with an aqueous environment. In addition, such hydrogels can be used as delivery vehicles for therapeutic agents.
TL;DR: A method for the preparation of polyionic hydrogels from the complexation of chitosan and xanthan is reported, and electronic microscopy studies have shown the formation of a fibrilar structure.
Patent•
04 Sep 1998
TL;DR: In this paper, the chemical surface treatments and methods for making the calcium phosphate coatings are disclosed, including dilute hydrogels such as phema to reinforce the inorganic structure and enhance the mechanical strength of the coatings.
Abstract: This invention encompasses porous, nanocrystalline, biomimetic calcium phosphate coatings of the order of 2-30 microns that can be grown on metal implants. The chemical surface treatments and methods for making the calcium phosphate coatings are disclosed. Post treatment with dilute hydrogels such as phema reinforce the inorganic structure and enhance the mechanical strength of the coatings. Methods are also disclosed for adsorbing or covalently attaching growth factor proteins to derivatives of the hydrogel coated calcium phosphate coatings. Such hydrogel reinforced calcium phosphate coatings show equivalent bone tissue growth as the currently used implants and are easily resorbed. This property in combination with the immobilized growth factors is expected to enhance the process of osseointegration of the disclosed coatings.
TL;DR: The attachment and growth of fibroblast cells (L-929) on the hydrogels were studied with a cell culture method and the attached cells were able not only to remain viable but also to proliferate.
Abstract: Hydrogels were prepared from poly(vinyl alcohol) and chitosan in various blend ratios. The water contents of the hydrogels were in the range of 65 to 75 wt %. The attachment and growth of fibroblast cells (L-929) on the hydrogels were studied with a cell culture method. On the hydrogels with more than 15 wt % chitosan content, the attached cells were able not only to remain viable but also to proliferate. The relative cell attachment after incubation for 30 h increased with increasing chitosan content in the hydrogels. Cell attachment and growth on the hydrogel with 40 wt % chitosan content exceeded those on collagen, a widely-used mammalian cell culture substrate. The morphology of the cells attached onto the hydrogels with a lower chitosan content was spherical, but in hydrogels with more than 15 wt % chitosan content, the number of spindle-shaped cells increased with increasing chitosan content.
TL;DR: It was concluded that drug diffusion may be impeded by associated drug binding, especially in IPN hydrogels containing high amounts of PAA.
TL;DR: Novel pH-sensitive hydrogels were synthesized by copolymerization of N,N-dimethylacrylamide, tert.-butylacryamide, acrylic acid, 4,4'-di(methacryloylamino)azobenzene, and N-alkanoyl, O-methACryloyslhydroxylamines to study the kinetics of swelling of cross-linked polymers.
Patent•
23 Jan 1998
TL;DR: In this paper, a degradable PEG hydrogel is described that, upon hydrolysis, releases conjugates of substantially non-peptidic polymers and biologically active molecules.
Abstract: A degradable PEG hydrogel is described that, upon hydrolysis, releases conjugates of substantially non-peptidic polymers and biologically active molecules. For example, PEG and protein conjugates can be released in vivo from the hydrogels for therapeutic application.
TL;DR: This paper describes synthesis and characterization of two types of novel degradable poly(ethylene glycol) (PEG) hydrogels with potential utility as delivery carriers for bioactive drugs.
TL;DR: Cross-linked gelatin hydrogels were found to be appropriate release systems for medium-term sustained delivery of biologically active epidermal growth factor (EGF), but release characteristics were strongly dependent on the nature of the protein which was incorporated.
Patent•
23 Jan 1998
TL;DR: In this article, the authors proposed a method for synthesizing hydrogels of cross-linked poly(ethylene) glycol (PEG) structures, which can be prepared by reacting two different PEG derivatives at the chain ends that react with each other to form new covalent linkages between polymer chains.
Abstract: This invention relates to hydrolytically degradable gels of cross-linked poly(ethylene) glycol (PEG) structures. Addition of water causes these cross-linked structures to swell and become hydrogels. The hydrogels can be prepared by reacting two different PEG derivatives containing functional moieties at the chain ends that react with each other to form new covalent linkages between polymer chains. The PEG derivatives are chosen to provide covalent linkages within the cross-linked structure that are hydrolytically degradable. Hydrolytic degradation can provide for dissolution of the gel components and for controlled release of trapped molecules, including drugs. Reagents other than PEG can be avoided. The hydrolysis rates can be controlled by varying atoms adjacent to the hydrolytically degradable functional groups to provide substantially precise control for drug delivery in vivo.
TL;DR: In this article, a simplified method for the synthesis of thermosensitive porous hydrogels by a radical polymerization was presented and their swelling properties were examined experimentally, and it was found that these gels consisted of aggregated microgel particles, namely, a porous structure.
Abstract: The simplified method for the synthesis of thermosensitive porous hydrogels by a radical polymerization was presented and their swelling properties were examined experimentally. N,N-Diethylacrylamide (DEAAm) or N-isopropylacrylamide (NIPAm) as primary monomers and N,N′-methylenebisacrylamide (BIS) as a crosslinker were used. They were polymerized in water at various temperatures above the lower critical solution temperature (LCST) of poly-DEAAm (ca. 32°C) or poly-NIPAm (ca. 31°C) by using N,N,N′,N′-,tetramethylethylenediamine (TEMED) and ammonium peroxsodisulfate (APS) as the polymerization accelerator and initiator, respectively. From the observation by a scanning electron microscope, it was found that these gels consisted of aggregated microgel particles, namely, a porous structure. The gels swelled below their LCSTs, and the swelling degree increased with lowering temperature. Furthermore, the gels swelled or shrank very fast in response to the change in temperature, and the shrinking rate was larger than the swelling rate. Such swelling properties and mechanical properties depended on the porous structure of the gels such as the size of the microgels and the pore volume, which largely changed with the synthesis temperature and the component of the primary monomer. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 895–906, 1998
TL;DR: In this paper, a new expression which describes the retardation of solutes within stiff-chained, swollen hydrogels was developed based on the idea that solute transport is determined by the probability of the solute finding an opening between the polymer chains greater than the radius of the molecule.
TL;DR: PEG-hydrogel membranes were prepared by the irradiation (> 300 nm) of aqueous solutions of photosensitive 4-armed PEG (nominal molecular weight of 20000) in the absence of photo-initiators, and were highly swellable with equilibrium volume fractions ranging from 0.02 to 0.05.
TL;DR: The swelling behavior of these gels in deionized water at 37 °C indicated that the gels prepared from PEG star Poly(ethylene glycol) star polymers with a small number of long arms swelled to a greater extent than those prepared fromPEG star polymer with a large number of short arms.
Abstract: Poly(ethylene glycol) (PEG) star polymer hydrogels were prepared by γ-irradiation of aqueous solutions of star PEG polymers The swelling behavior of these gels in deionized water at 37 °C indicated that the gels prepared from PEG star polymers with a small number of long arms swelled to a greater extent than those prepared from PEG star polymers with a large number of short arms PEG star polymers and branched PEG polymers were modified to incorporate acrylate groups on the ends of the polymer arms These acrylated star or branched polymers were copolymerized with poly(ethylene glycol) diacrylate in the presence of UV light The ensuing materials swelled to a greater extent than hydrogels prepared without acrylated star or branched PEG polymers Number-average molecular weights were calculated using several rubber elasticity-based theories
TL;DR: A new method of preparing ionically cross-linked polyphosphazene hydrogel microspheres which enables effective control over microsphere size distribution has been developed and it was demonstrated that the method enables efficient microencapsulation of proteins.