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PubMed2001

Enhanced formation of fibrosis in a rabbit aneurysm by gelatin hydrogel incorporating basic fibroblast growth factor.

OBJECTIVE: This study was undertaken to analyze whether the controlled release of basic fibroblast growth factor (bFGF) can promote intrasaccular thrombosis in an experimental aneurysmal model. METHODS: Carotid aneurysms were constructed in 80 rabbits with venous pouches and treated by placing gelatin hydrogels into each aneurysm incorporating 0, 25, 50, or 100 microg of bFGF or incorporating 100 microg of bFGF with different water contents. In the controls, the venous pouches either were not treated or were treated with gauze alone. Gelatin hydrogel was used for the controlled release of bFGF into the aneurysms. The formation of fibrosis in the aneurysms was histologically viewed to assess the area occupied by the fibrous tissues at 3 and 6 weeks after the hydrogel application. The effect of the bFGF dose and water content on obliterating the aneurysm by the hydrogels incorporating bFGF was also investigated. RESULTS: Six weeks after the application of gelatin hydrogels with a water content of 95 wt% incorporating 100 microg of bFGF, the lateral pouch orifice was completely closed, obliterating the aneurysm at the level of tissue appearance, in contrast to hydrogels incorporating lower doses of bFGF and other control agents. The venous pouch aneurysm was histologically occupied with the newly formed fibrous tissue, and the fibrous tissue area and percentage of the aneurysmal lumen occupied by the fibrosis-gauze complex were significantly larger than those of other hydrogel applications (P < 0.05). The neointima tissue was homogeneously covered with a monolayer of Factor VIII-positive cells. The fact that there was no difference in the water content in the fibrosis formation induced by the bFGF-incorporated gelatin hydrogels indicated that the hydrogel biodegradability did not affect the obliteration of the aneurysm. CONCLUSION: Local controlled release of bFGF stimulated the formation of in vivo fibrosis, resulting in obliteration of the aneurysm. The long-term results of the fibrous organization remain speculative.

Animals↗
PubMedDate not supplied

Orbital complications of hydrogel scleral buckles.

PURPOSE: Hydrogel is a biocompatible osmotic expansile material used in contact lenses, scleral buckles, and orbital expanders. Three unique complications from hydrogel scleral buckle use are presented: orbital cellulitis mimicry, fornical shortening with orbital prosthetic intolerance, and orbital pseudotumor. METHODS: A retrospective chart review was conducted on three subjects with unknown hydrogel scleral buckle complications at a tertiary care oculoplastics practice. Demographics, imaging studies, and pathologic specimens were reviewed. RESULTS: All three patients had a history of encircling hydrogel scleral buckle placed for retinal detachment. The mean time from implantation to presentation was 10.7 years (range, 7 to 15 years). One patient had an onset of presumed orbital cellulitis caused by an enlarged buckle and no abscess. The second patient had inability to wear an evisceration prosthesis as the result of a shortened fornix from an enlarged hydrogel scleral buckle implant. The third patient presented with an orbital mass caused by the enlarged implant. In all cases, surgical removal of the expanded buckle relieved the patient's symptoms. CONCLUSIONS: Although the hydrogel scleral band is designed to expand in a controlled fashion, overexpansion can occur. Expansion can cause buckle extrusion, prosthetic intolerance, a pseudo-orbital cellulitis, or orbital pseudotumor and may be due to a chemical change in the hydrogel polymer. Patients with hydrogel scleral buckles should be followed long-term for possible complications. Patients with newer uses of hydrogel, such as orbital expanders, should also be observed for long-term complications.

Adult↗
PubMed2002

In vitro release behavior of insulin from biodegradable hybrid hydrogel networks of polysaccharide and synthetic biodegradable polyester.

The controlled release of insulin from a series of biodegradable hybrid hydrogel network containing dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of composition ratio was investigated. Laser confocal scanning microscope was used to understand the insulin dispersion and release mechanism in the hydrogels. We found that the dispersion of insulin in the hydrogel network appeared to become less homogeneous as the PDLLAM composition in the hydrogel increased. The increase in hydrogel degradability imparted by PDLLAM incorporation shifted the hydrogel to a more open structure at a later release time, which facilitated the release rate and extent of insulin. From the result of release kinetics study (i.e., diffusion coefficient), insulin release occurred through diffusion and degradation controlled mechanisms. In addition, a comparison of the release characteristics of indomethacin, insulin and bovine serum albumin from the hydrogel network showed that the following parameters determined the release kinetics: drug molecular weight and size, hydrogel swellability and degradability, drug solubility in water and the hydrophobic interaction between drugs and the hydrogel network.

Biocompatible Materials↗
PubMed1994

Inhibition of platelet deposition and lysis of intracoronary thrombus during balloon angioplasty using urokinase-coated hydrogel balloons.

BACKGROUND: Conventional balloon angioplasty of intracoronary thrombus is associated with a high incidence of abrupt closure, distal embolization, and no-reflow phenomenon. The purpose of this study was to assess a new technique for treating intracoronary thrombus consisting of the local delivery of urokinase directly to the angioplasty site with urokinase-coated hydrogel balloons. METHODS AND RESULTS: We assessed local urokinase delivery using hydrogel balloons in four protocols. First, we evaluated the pharmacokinetics of urokinase delivery in vitro using 125I-labeled urokinase to measure drug loading onto hydrogel balloons, drug retention by the hydrogel polymer during blood exposure, and drug transfer from the balloon surface to the arterial wall during balloon dilatation. Second, we measured 125I-urokinase washoff from the hydrogel balloon in the intact circulation and intramural drug delivery during in vivo balloon angioplasty in 10 anesthetized New Zealand rabbits. Third, we assessed the effect of local urokinase delivery on 111In-labeled platelet deposition after balloon angioplasty in vivo in 13 porcine carotid or iliac arteries dilated with urokinase-coated balloons and compared them with contralateral control arteries dilated with saline-coated balloons. Finally, we determined the clinical efficacy of urokinase-coated balloons in 15 patients with intracoronary thrombus, including 7 who demonstrated abrupt thrombotic closure after conventional angioplasty. Between 241 and 1509 U urokinase could be loaded onto hydrogel balloons ranging in size from 2 to 8 mm. In vitro and in vivo studies demonstrated that hydrogel balloons absorbed significantly more urokinase and demonstrated less drug wash-off than nonhydrogel balloons (P < .01). Similarly, both in vitro and in vivo studies demonstrated urokinase transfer from the hydrogel to the arterial wall during balloon angioplasty, with greater intramural drug deposition with larger balloons (P < .01). Local urokinase delivery after in vivo porcine angioplasty decreased 111In-labeled platelet deposition by 47% compared with contralateral control vessels (P = .03). Use of urokinase-coated balloons in patients with intracoronary thrombus resulted in thrombus dissolution and reversal of abrupt closure in all cases, without evidence of distal embolization. CONCLUSIONS: With the use of hydrogel-coated balloons, urokinase can be delivered locally to an angioplasty site. This technique decreases platelet deposition after in vivo balloon angioplasty and is efficacious in treating intracoronary thrombus in patients, including those with abrupt thrombotic closure.

Adult↗
PubMed2000

pH-sensitivity of fast responsive superporous hydrogels.

Stimuli-sensitive hydrogels (or smart hydrogels) are hydrogels that swell or shrink in response to small changes in environmental conditions in which they are placed. While the extent of swelling or shrinking may be large, the kinetics of such changes is slow, since the diffusion of water into and out of the hydrogel is a slow process. To obtain fast responses, we have prepared superporous hydrogels (SPHs) that can swell or shrink extremely fast regardless of their dimensions. The swelling and shrinking are orders of magnitude faster than expected for a nonporous hydrogel of the same dimensions. Water molecules are taken up into the SPHs by capillary forces, and this makes water uptake much faster than diffusion. The swelling ratio of the poly(acrylamide-co-acrylic acid) (p(AM-co-AA)) SPHs was dependent on the pH and ionic strength of the medium. The effect of pH was most pronounced and the effect of ionic strength was observed at all pH values. SPHs made at pH around 5 showed transient maximum swelling when exposed to pH 1.2 medium due to the transient low hydrogen ion concentration inside the swelling SPHs. The p(AM-co-AA) SPHs showed repeated swelling and shrinking by alternating the medium pH between 1.2 and 7.5, and the changes in swelling ratio was quite fast occurring in a matter of a minute. This fast sensitivity may make the stimuli sensitive hydrogels useful in many applications not previously possible. These materials can be used for applications where a single-piece hydrogel is more advantageous than hydrogel microparticulates.

Acrylamides↗
PubMed2004

Anti-inflammatory drug delivery from hyaluronic acid hydrogels.

Two different types of hyaluronic acid (HA) hydrogels were synthesized by crosslinking HA with divinyl sulfone (DVS) and poly(ethylene glycol)-divinyl sulfone (VS-PEG-VS). Vitamin E succinate (VES), an anti-inflammatory drug, and bovine serum albumin (BSA), a model of anti-inflammatory protein drugs, were loaded into the gels and their release kinetics were measured in vitro. VES and BSA released with a burst from both HA hydrogels during the first few hours, and release continued gradually for several days. The rate of release from HA-VS-PEG-VS-HA hydrogels was faster than that from HA-DVS-HA hydrogels, presumably due to the lower crosslink density in the former. The anti-inflammatory action of released VES was tested by incubating peripheral blood mononuclear cells (PBMC) on HA hydrogels with and without VES in the gel. The number of cells adhering on HA hydrogels was very low compared to that on tissue culture polystyrene (TCPS), which might be one of the important advantages of using HA hydrogels for implant coatings or tissue engineering applications. ELISA test results showed that the tumor necrosis factor-alpha (TNF-alpha) concentration was very low in the supernatant of the wells containing the HA hydrogel with VES in contact with the activated macrophages compared to that without VES. This is probably the effect of the released VES reducing the production of anti-inflammatory cytokine, TNF-alpha. HA hydrogels containing anti-inflammatory drugs may have potential for use in tissue engineering and also as biocompatible coatings of implants.

Animals↗
PubMed2005

In vivo degradability of hydrogels prepared from different gelatins by various cross-linking methods.

This study is an investigation to evaluate the in vivo degradation of gelatin hydrogels in terms of their number of cross-links. Various hydrogels were prepared from acidic gelatin, extracted from bovine bone, porcine skin or fish scale, and basic gelatin, extracted from porcine skin, through four types of cross-linking methods, i.e., glutaraldehyde (GA) or dehydrothermal treatment and ultraviolet (UV) or electron beam irradiation. The water content of hydrogels and their number of cross-links, calculated from the tensile modulus of hydrogels, were evaluated as the measure of hydrogel cross-linking extent. Following subcutaneous implantation of 125I-labeled gelatin hydrogels into mice, the radioactivity remaining was measured at different time intervals to assess the in vivo degradability of hydrogels. Irrespective of the gelatin type and cross-linking method, a good correlation was found between the in vivo degradability of hydrogels and their number of cross-links, which is different from the correlation to their water content. This finding indicates that the degradability of hydrogels is governed by their number of cross-links.

Absorbable Implants↗
PubMedDate not supplied

Chitosan-polyvinyl pyrrolidone hydrogels as candidate for islet immunoisolation: in vitro biocompatibility evaluation.

The success of immunoisolation devices for islet transplantation depends on the nature of semipermeable membranes, which permit the crossover of micronutrients, glucose, and insulin and prevent the entry of immunocytes and other transplant rejection mechanisms. In the present study we examined the properties of chitosan-polyvinyl pyrrolidone (PVP) hydrogels for possible application as an immunoisolation device. Hydrogels with two different proportions of chitosan-PVP (M1 1:1 and M2 2:1, v/v) were synthesized by cross-linking with glutaraldehyde. Hydrogels were characterized for their hydrophilic nature, protein adsorption, diffusion properties, cytotoxicity, and islet compatibility. Hydrogel membranes were found to be hydrophilic as determined by high octane contact angle value (M1: 142.9 +/- 0.46; M2: 143.6 +/- 0.49). Protein adsorption on the hydrogels was found to be low (0.0143 +/- 0.0027 mg for M1 and 0.0136 +/- 0.0049 mg for M2) compared to tissue culture polystyrene (TCPS) (0.0434 +/- 0.001 mg) and pure chitosan (0.0214 +/- 0.0025 mg) control. Hydrogel M1 was tested as a representative for diffusion studies. M1 allowed regulated transport of insulin and did not allow anti-insulin antibodies to pass through. In vitro biocompatibility of M1 and M2 was found to be excellent with no cytotoxic effects on the HeLa cells as determined by MTT and NR assay. Mouse islets cultured on the hydrogel membranes retained their integrity and intact morphology as assessed by image analysis study. Viability of islets cultured on hydrogels was comparable to that of controls (M1: 97%; M2: 90.4%) as assessed by trypan blue dye exclusion test. Islets retained their functionality when cultured on hydrogels, as judged by insulin secretion in response to glucose challenge (16.0 mM). Although in vivo experiments are awaited, the present study provides sufficient documentation to consider chitosan-PVP membranes as potential candidates for immunoisolation of islets.

Adsorption↗
PubMed2001

In vitro expression of cartilage-specific markers by chondrocytes on a biocompatible hydrogel: implications for engineering cartilage tissue.

Natural cartilage tissue has a limited self-regenerative capacity; thus, strategies to replenish the lost cartilage are desired in reconstructive and plastic surgery. Tissue-engineered cartilage using biodegradable polymeric scaffolds is one such approach gaining wide attention. We have earlier demonstrated the biocompatible nature and ability of chitosan-gelatin hydrogel to maintain differentiated populations of respiratory epithelial cells. The aim of the present study was to evaluate its suitability as a substratum for inducing chondrocyte growth and differentiation. Electron microscopic (SEM) analysis of freeze-dried hydrogels showed a highly porous morphology with interconnections as seen in cross section. Chondrocytes were observed to attach and exhibited a differentiated phenotype with proper cell-cell contact on three-dimensional freeze-dried hydrogels. When cultured on two-dimensional hydrogel films they showed higher growth rates (4-6%) compared with a polystyrene (TCPS) control until 6 days (p > 0.05), which slowed down after 10 days. Immunofluorescent microscopic studies revealed that chondrocytes on hydrogel films exhibited comparable expression of beta1 integrin (CD29) to TCPS controls, indicating the ability of the hydrogel substrate to maintain normal expression of beta1 integrin. RT-PCR analysis of chondrocytes grown on hydrogel films showed that chondrocytes express the mRNA for extracellular matrix proteins such as collagen type IIalpha1 (COL IIalpha1), COL III, COL IXalpha3. Expression of COL I was less prominent than COL II as indication of differentiation. Expression of COL X could not be detected, suggesting an absence of chondrocyte hypertrophy. Chondrocytes also showed weak mRNA expression of aggrecan, a cartilage-specific proteoglycan. All of these results point out the ability of the chitosan-gelatin hydrogel to induce the expression of mRNAs for cartilage-specific extracellular matrix proteins by nasal septal chondrocytes. This hydrogel needs to be further evaluated for its ability to support chondrocyte-specific marker expression to explore the possibility of forming a tissue resembling natural cartilage in vitro.

Aggrecans↗
PubMed1997

Hydrogels containing peptide or aminosugar sequences implanted into the rat brain: influence on cellular migration and axonal growth.

Biocompatible polymer matrices for implantation into lesion sites in the brain were synthesized by incorporating peptide or aminosugar sequences into N-(2-hydroxypropyl)methacrylamide (HPMA) hydrogels. RGD peptide sequences were chemically linked to the hydrogel backbone via a glycylglycine spacer; aminosugars were glucosamine (NHGlc) or N-acetylglucosamine residues. Unmodified or sequence containing HPMA hydrogels were implanted into the lesioned optic tract or cerebral cortex of juvenile (17- to 19-day-old) or adult rat brains, respectively. After 10-12 months host animals were perfused and the brains were processed for immunohistochemistry using antibodies to neurofilaments (RT97), laminin, glial fibrillary acidic protein (GFAP), carbonic anhydrase II (CAII), S100 protein, macrophages (ED1), and myelin basic protein (MBP). Unmodified (control) HPMA hydrogels contained no cellular infiltration or axonal growth. Peptide (RGD)- and aminosugar-modified hydrogels showed increased adhesion properties with host neural tissue, were vascularized, and were infiltrated by host nonneuronal cells. Astrocytes (GFAP+) and macrophages (ED1(+)) were the major cell types seen within modified HPMA hydrogels, the largest numbers being found in RGD-containing polymers. CAII+ oligodendroglia were not seen within any of the hydrogel matrices. RT97(+)/MBP- axons grew into both the RGD and NHGlc hydrogel matrices for small distances. The number of axons was greatest in hydrogels implanted into cerebral cortex but in both cortex and optic tract implants the highest density of axons was seen in polymers containing RGD. The findings of this study are discussed in the context of CNS tissue replacement and the construction of bioactive scaffolds to promote regenerative axonal growth across areas of injury in the brain and spinal cord.

Animals↗
PubMed2007

Amphoteric surface hydrogels derived from hydrogen-bonded multilayers: reversible loading of dyes and macromolecules.

We used hydrogen-bonded multilayers of poly(N-vinylpyrrolidone) (PVPON) and poly(methacrylic acid) (PMAA) as precursors for producing surface-bound hydrogels and studied their pH-dependent swelling and protein uptake behavior using in situ attenuated total reflection Fourier transform infrared spectroscopy and in situ ellipsometry. The hydrogels were produced by selective chemical cross-linking between PMAA units using carbodiimide chemistry and ethylenediamine (EDA) as a cross-linking reagent, followed by complete removal of PVPON from the film obtained by exposing the film to pH 7.5. As shown by in situ ellipsometry, hydrogels exhibit distinctive polyampholytic swelling as a function of pH, with minimum swelling at pH 4.2-5.7, and increased film thickness at both lower and higher pH values. Film swelling at lower pH values occurs as a result of the presence of amino groups within the hydrogels, which originate from the one-end attachment of the EDA cross-linker to PMAA chains. The pH-switching of hydrogel swelling was fast and reversible. The degree of hydrogel swelling could be also controlled by varying the time allowed for cross-linking. The produced hydrogels were able to absorb large amounts of dyes and proteins of opposite charge reversibly, in response to pH variations. Finally, we demonstrate that proteins included within the hydrogel can easily be replaced with linear polycations. These surface hydrogels hold promise for bioseparation and controlled delivery applications.

Journal Article↗
PubMed2006

Hydrogel behavior of a sugar-based gelator by introduction of an unsaturated moiety as a hydrophobic group.

The new sugar-based gelators 1 and 2 were synthesized, and their gelation abilities were evaluated in organic solvents and in water. Compound 1 gelates both water and organic solvents whereas 2 gelates only organic solvents. Superstructural difference between hydrogel 1 and organogel 2 was investigated by CD, TEM, AFM, 1H NMR and XRD. Hydrogel 1 displays a well-developed helical ribbon structure with 20-150 nm diameter and a length of several hundred microm whereas organogel 2 shows a twisted fiber structure of diameter 20 nm. CD measurements of hydrogel 1 and organogel 2 indicate that hydrogel 1 maintains a well-ordered chiral structure whereas organogel 2 maintains a relatively disordered chiral structure. The 1H NMR and XRD results suggest that the hydrophobic interaction in hydrogel 1 are relatively weak, with a relatively small region interdigitated between lipophilic alkyl groups. In addition, upon irradiation at 254 nm wavelength, hydrogel 1 reveals a red coloration at 540 nm. These results indicate that the self-assembled hydrogel 1 was polymerized by UV-irradiation. The intensity of the CD spectrum of the polymerized hydrogel markedly decreased. This result indicates that upon polymerization the highly ordered chiral structure of hydrogel 1 changes to a disordered molecular packing structure.

Journal Article↗
PubMed2003

Long-term effects of polyacrylamide hydrogel on human breast tissue.

Polyacrylamide hydrogel is an atoxic, stable, nonresorbable sterile watery gel consisting of approximately 2.5% cross-linked polyacrylamide and nonpyrogenic water. Polyacrylamide hydrogel is widely used in ophthalmic operations, drug treatment, food packaging products, and water purification. In the former Soviet Union, polyacrylamide hydrogel has been used in plastic and aesthetic surgery for more than 10 years, and Kiev City Hospital treats approximately 300 women a year for breast augmentation using the polyacrylamide hydrogel Interfall (Contura SA, Montreux, Switzerland). Capsule shrinkage following these injections has never been observed. The authors examined breast tissue samples from a total of 27 women who had polyacrylamide hydrogel injected at Kiev City Hospital up to 8 years and 10 months earlier. Age at operation, duration of polyacrylamide hydrogel implantation, history of possible side effects to the gel injection, other intercurrent diseases, the reason for present open breast operation, and breast palpation findings before operation were in each case compared with the histological findings on samples taken from breast tissue bordering the gel. The gel presented itself as a dark violet, homogenous mass with a rounded or ragged outline in large or medium-size deposits and as elongated strands, which mimicked the extracellular matrix, in small deposits. Histological findings of the breast tissue bordering the gel showed three different patterns: large collections of gel gave rise to a thick, soft-looking cellular membrane of macrophages and foreign-body giant cells; medium-size deposits were surrounded by just a thin layer of macrophages; and small deposits were not associated with any reaction in the surrounding tissue. Projections of the cellular soft membrane, known as granulomas, were seen in six patients. The granulomas were composed of macrophages, foreign-body giant cells, lymphocytes, and blood cells. A thin layer of fibrous connective tissue was occasionally present around the foreign-body membrane, but the thick fibrous capsule, which has been described in connection with silicone implants, was completely absent. The gel changes could be correlated to neither time since gel injection nor a history of recent injury or inflammation. It is concluded that the polyacrylamide hydrogel Interfall, which has been used in the former Soviet Union, is stable over time, nondegradable, confined to the breast, and diffusion and migration resistant. When the hydrogel is injected in medium-size or large quantities a cellular foreign-body reaction occurs, but in small amounts it is capable of splitting up individual connective tissue fibers and fat cells, substituting for the extracellular connective tissue matrix without eliciting any foreign-body reaction. As far as these data are concerned, polyacrylamide hydrogel is well tolerated by the breast and does not give rise to severe fibrosis, pain, or capsule shrinkage. However, to determine safety with more certainty, a larger sample size would be necessary.

Acrylic Resins↗
PubMedDate not supplied

Experimental corneal neovascularization by basic fibroblast growth factor incorporated into gelatin hydrogel.

The study was designed to investigate the feasibility of using an acidic gelatin hydrogel as a biodegradable vehicle for basic fibroblast growth factor (bFGF). bFGF was incorporated by polyion complexation into a biodegradable hydrogel prepared by cross-linking acidic gelatin with the isoelectric point of 4.9. The dried hydrogel (sized to 2x1 mm) was hydrated with bFGF aqueous solution including different doses of bFGF (20, 50, 125, 250 and 500 ng) and implanted into a rabbit corneal pocket (2.5x2 mm). As a control group, the gelatin hydrogel without bFGF or bFGF alone (500 ng) was used. Corneal angiogenesis was evaluated by biomicroscopy, corneal fluorescein angiography and histology for 21 days. Photographs were taken and corneal angiogenesis was evaluated by image analysis. The hydrogel degraded with time after its implantation into the corneal pocket. Experimental eyes receiving the hydrogel containing more than 50 ng of bFGF demonstrated significant corneal angiogenesis. Control eyes and eyes receiving the hydrogel containing 20 ng of bFGF showed no corneal angiogenesis. Corneal angiogenesis, which occurred on the 3rd or 4th day after implantation, reached maximal growth on about day 7 and regressed from day 10 after implantation. The area of angiogenesis showed a dose-dependency on bFGF. The gelatin hydrogel itself induced neither angiogenesis nor inflammation. These results suggested that acidic gelatin hydrogel releases bioactive bFGF with its biodegradation, resulting in corneal neovascularization.

Absorbable Implants↗
PubMed1998

Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein.

Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross-linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP-2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2-incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP-2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back of mice, the radioactivity remaining in the hydrogels was measured to estimate the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution form was cleared from the injected site within one day, completely disappearing within 3 days. Ectopic bone formation studies demonstrated that BMP-2-incorporating gelatin hydrogels exhibited a more potent ability for bone induction than solution injection of BMP-2. This finding indicates that enhanced retention of BMP-2 is promotes its ability to induce ectopic bone formation.

Animals↗
PubMed1998

Polymeric hydrogels placed into a fimbria-fornix lesion cavity promote fiber (re)growth: a morphological study in the rat.

To examine the regeneration capacity of dorsal septohippocampal neurons in the presence of an artificial growth-promoting substrate, biocompatible polymeric hydrogels were implanted between the septum and the hippocampus in a fimbria-fornix lesion cavity. Unmodified (control) or aminosugar-containing (glucosamines or N-acetyl-glucosamines) hydrogels were implanted immediately or ten days after the lesions. Six months later, brain sections were processed for cresyl-violet, acetylcholinesterase, and immunocytochemical (glial fibrillary acidic protein, protein S100, neurofilaments, laminin, fibronectin) staining. All hydrogels were well integrated in the brain, constituting a stable bridge between the septum and the hippocampus. Weak gliosis occasionally surrounded the hydrogel in rats from the immediate-implantation group, whereas a more pronounced gliosis was observed in those from the delayed-implantation group. The hydrogels contained blood vessels and were invaded by host cells including astrocytes. Astrocytes formed a loose tissue network filling the porous structure of the hydrogels. Within the hydrogels, laminin-, fibronectin- or neurofilaments-immunopositive networks were also observed. Moreover, numerous acetylcholinesterase-positive fibers penetrated into the hydrogels from the septal, cortical and striatal areas. Fibre penetration was most important in the N-acetylglucosamines-containing hydrogels. Despite these features, the hippocampus failed to show any increase of acetylcholinesterase-staining as compared to that seen in lesion-only rats. These results confirm the regeneration capacity of severed septohippocampal neurons into polymeric substrates used as a bridge inserted in a fimbria-fornix lesion cavity. As such, biomaterials might be of clinical interest not only in the case of spinal cord sections, but also in cases of brain trauma.

Journal Article↗
PubMed2005

Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor.

Synthetic hydrogel mimics of the extracellular matrix (ECM) were created by crosslinking a thiol-modified analog of heparin with thiol-modified hyaluronan (HA) or chondroitin sulfate (CS) with poly(ethylene glycol) diacrylate (PEGDA). The covalently bound heparin provided a crosslinkable analog of a heparan sulfate proteoglycan, thus providing a multivalent biomaterial capable of controlled release of basic fibroblast growth factor (bFGF). Hydrogels contained >97% water and formed rapidly in <10min. With as little as 1% (w/w) covalently bound heparin (relative to total glycosaminoglycan content), the rate of release of bFGF in vitro was substantially reduced. Total bFGF released increased with lower percentages of heparin; essentially quantitative release of bFGF was observed from heparin-free hydrogels. Moreover, the hydrogel-released bFGF retained 55% of its biological activity for up to 28 days as determined by a cell proliferation assay. Finally, when these hydrogels were implanted into subcutaneous pockets in Balb/c mice, neovascularization increased dramatically with HA and CS hydrogels that contained both bFGF and crosslinked heparin. In contrast, hydrogels lacking bFGF or crosslinked heparin showed little increase in neovascularization. Thus, covalently linked, heparin-containing glycosaminoglycan hydrogels that can be injected and crosslinked in situ constitute highly promising new materials for controlled release of heparin-binding growth factors in vivo.

Animals↗
PubMed2002

Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering.

Photoactive polyvinyl alcohol hydrogels (PVA) have been investigated for use as tissue engineering scaffolds. These materials allow in situ polymerization for minimally invasive implantation methods. The mechanical properties of these materials can be tailored for a variety of soft tissue applications. The Young's modulus and ultimate tensile strength of PVA hydrogels are increased with increasing polymer concentration, and highly elastic hydrogels can be formed by altering the number of crosslinkable groups per chain. Fibroblasts homogeneously seeded within 3 mm thick PVA hydrogels remained viable throughout 2 weeks in culture, with no differences in viability across the thickness of the hydrogel. Cells seeded within the PVA hydrogels also produce extracellular matrix proteins, as indicated by the production of hydroxyproline during culture. Intrinsically cell non-adhesive, these PVA hydrogels were functionalized with the cell-adhesive peptide RGDS and found to support the attachment and spreading of fibroblasts in a dose-dependent manner. These results suggest that photopolymerizable PVA hydrogels are promising for tissue engineering applications.

Biocompatible Materials↗