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PubMed1996

In vitro platelet adhesion to nonionic and ionic hydrogels with different water contents.

To investigate in vitro platelet adhesion to hydrogels, using electron-beam irradiation, polymer reaction, and radical polymerization, hydrogels were synthesized to have a wide range of water content. The nonionic synthesized hydrogels include polyacrylamide (PAAm), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(N-vinyl pyrrolidone), and poly(methoxy-PEG methacrylate) while the ionic hydrogels were crosslinked poly(AAm-acrylic acid) and poly(AAm-dimethylaminoethyl methacrylate) copolymers. Adhesion of washed rabbit platelets to these hydrogels were studied in phosphate-buffered saline for 30 min. In the case of PVA and PAAm hydrogels, platelet adhesion also was conducted in the presence of proteins. The protein sorption into PVA hydrogel was studied by fluorescent spectroscopy. It was found that all the nonionic hydrogels exhibited a lower level of platelet adhesion than did conventional hydrophobic polymers, such as medical-grade poly(vinyl chloride), polyurethane, and silicone, and they exhibited the minimum platelet adhesion at a water content of around 90%. PAAm and PEG hydrogels had the weakest interaction with platelets when the water content was lower than 90%. PVA hydrogel showed the highest platelet adhesion in the low-water-content region, but the platelet adhesion was greatly reduced in the presence of proteins. Significant protein sorption was noted when the water content of PVA hydrogel was as high as 80%. Introduction of a positive charge into the PAAm hydrogel promoted platelet adhesion whereas the negative charge introduced into the hydrogel slightly reduced the number of adhered platelets.

Adsorption↗

PubMed2005

Regional radiochemotherapy using in situ hydrogel.

PURPOSE: To evaluate the feasibility of regional radiochemotherapy of mammary tumors using in situ hydrogel loaded with cisplatin (CDDP) and rhenium-188 ((188)Re). METHODS: Sodium alginate (SA) and calcium chloride were used to create a hydrogel for delivery of CDDP and (188)Re. In vitro studies were performed to evaluate cytotoxic effects of (188)Re-hydrogel and sustained-release ability of the CDDP-hydrogel. Tumor-bearing rats were injected with (188)Re-hydrogel (0.5-1 mCi/rat), (188)Re-perrhenate (0.5-1 mCi/rat, intratumoral, I.T.), CDDP-hydrogel (3 mg/kg), and (188)Re-hydrogel loaded with CDDP (3 mg/kg body weight, 0.5-1 mCi/rat), respectively, and groups receiving (188)Re were imaged at 24 and 48 h postinjection. Tumor volume, body weight, imaging, and kidney function were assessed as required for each group. RESULTS: Successful formation of the hydrogel was demonstrated by cytotoxic effects of (188)Re-hydrogel and slow release of CDDP-hydrogel in vitro. Tumor volume measurements showed significant delay in tumor growth in treated vs. control groups with minimal variation in normal kidney function for the CDDP-hydrogel group. Scintigraphic images indicated localization of (188)Re-hydrogel in the tumor site up to 48 h postinjection. CONCLUSIONS: Our data demonstrate the feasibility of using hydrogel for delivery of chemotherapeutics and radiation locally. This technique may have applications involving other contrast modalities as well as treatment in cases where tumors are inoperable.

Animals↗

PubMed2004

Attachment, proliferation, and migration of marrow stromal osteoblasts cultured on biomimetic hydrogels modified with an osteopontin-derived peptide.

We prepared oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with a rat osteopontin-derived peptide (ODP), Asp-Val-Asp-Val-Pro-Asp-Gly-Arg-Gly-Asp-Ser-Leu-Ala-Try-Gly (DVDVPDGRGDSLAYG), as well as Gly-Arg-Gly-Asp-Ser (GRGDS) and investigated the modulation of marrow stromal osteoblast function on the peptide-modified hydrogels. Osteoblast attachment was competitively inhibited by a soluble peptide suggesting that the interaction of osteoblasts with the hydrogel was ligand specific. The proliferation index of osteoblasts relative to the initial seeding density was similar on the hydrogels modified with ODP (1.18+/-0.13) and GRGDS (1.27+/-0.12). However, fibroblasts proliferated faster on GRGDS-modified hydrogels than on ODP-modified hydrogels as evidenced by the proliferation indices of 4.89+/-0.03 and 2.42+/-0.16, respectively. A megacolony migration assay conducted for 3 days with a seeding density of 53,000 cells/cm(2) showed that osteoblasts migrated to a longer distance on ODP-modified hydrogels (0.23+/-0.06 mm/day) than on hydrogels modified with GRGDS (0.15+/-0.02 mm/day). In addition, osteoblasts migrated faster than fibroblasts seeded at the same density on ODP-modified hydrogels (0.15+/-0.11 mm/day). The migration of osteoblasts on the peptide-modified hydrogels was dependent on the peptide concentration of the hydrogels resulting in an increased migration distance with increasing the peptide concentration for the concentrations tested. These results show that OPF-based biomimetic hydrogels hold promise for modulating cell proliferation and migration for specific applications by altering the specific ligand and its concentration in the hydrogels.

Animals↗

PubMed2001

Environment-sensitive hydrogels for drug delivery.

Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made.

Animals↗

PubMed2002

Local hemostasis during laparoscopic partial nephrectomy using biodegradable hydrogels: initial porcine results.

BACKGROUND AND PURPOSE: Despite the advance of laparoscopic partial nephrectomy, significant technical limitations remain with regard to control of bleeding and closure of the collecting system. An attractive approach on the horizon for local hemostatic and wound control is the use of local tissue sealants. To date, sealants remain largely derived from natural biologic products and are difficult to apply laparoscopically with precise local control. In this study, we examined the novel strategy of forming occlusive tissue-adherent hydrogels utilizing a synthetic biodegradable polyethylene glycol-lactide copolymer (PEG-lactide) as an in situ occlusive barrier for hemostasis and wound control. Specifically, the objects of this study were to determine if PEG-lactide hydrogels could be formed intraperitoneally on renal tissue, to test the adhesiveness of the hydrogels to injured renal parenchyma, and to evaluate the ability of adherent hydrogel barriers to limit renal parenchymal bleeding and collecting system leakage following renal pole amputation or wedge excision. MATERIALS AND METHODS: Five kidneys from three female pigs were used in a nonsurvival study. A standardized model for laparoscopic partial nephrectomy was created by performing wedge excision or polar amputation under vascular control using a laparoscopic Satinsky clamp. Bleeding briskness following injury was assessed utilizing a scoring system and free blood quantitated comparing a conventional "clamp and wait" strategy with an adherent hydrogel strategy. For the hydrogel group, PEG-lactide hydrogel primer and macromer were applied through laparoscopic ports. The hydrogel was polymerized using a xenon light source, and the pedicle clamp was released to observe for bleeding. A subsequent opposite polar injury was created to confirm renal perfusion and the sites were compared. The kidneys were removed, and the adhesion of the hydrogel to the renal parenchyma was examined. RESULTS: The PEG-lactide macromer was effectively applied to five kidneys following partial nephrectomy. In all cases, successful intraperitoneal in situ polymerization was achieved, with resultant hydrogel formation. Polymeric hydrogel adhesion to the cut renal parenchyma was assessed semiquantitatively following vigorous cyclic washing. In all cases, polymer gels remained adherent without any evidence of peeling, delamination, or separation from the underlying tissue surface. In the control group, the mean bleeding score was 2.63 +/- 0.48 v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). Blood loss in the control group was 56 +/- 5 ml v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). In an ex vivo retrograde ureteral perfusion, no leakage was observed at pressure as high as 100 mm Hg. CONCLUSIONS: In this feasibility study, a biodegradable PEG-lactide polymer system photopolymerized rapidly in situ on exposed renal parenchymal surfaces, forming adherent hydrogel barriers. When applied during vascular clamping, an adequate physical bond and patch-like cap was created to prevent bleeding at physiologic renal perfusion pressures. Use of locally applied occlusive hydrogels holds promise for hemostasis and local wound control during laparoscopic urologic procedures.

Absorbable Implants↗

PubMed2003

In vivo bone and soft tissue response to injectable, biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels.

This study was designed to assess in vivo bone and soft tissue behavior of novel oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels using a rabbit model. In vitro degradation of the OPF hydrogels was also investigated in order to compare with in vivo characteristics. Four groups of OPF hydrogel implants were synthesized by alternation of crosslinking density, poly(ethylene glycol) (PEG) block length of OPF, and cell-binding peptide content. The in vitro degradation rate of OPF hydrogels increased with decreasing crosslinking density of hydrogels, which was characterized by measuring weight loss and swelling ratio of hydrogels and medium pH change. Examination of histological sections of the subcutaneous and cranial implants showed that an uniform thin circumferential fibrous capsule was formed around the OPF hydrogel implants. Quantitative evaluation of the tissue response revealed that no statistical difference existed in capsule quality or thickness between implant groups, implantation sites or implantation times. At 4 weeks, there was a very limited number of inflammatory and multinuclear cells at the implant-fibrous capsule interface for all implants. However, at 12 weeks, OPF hydrogels with PEG block length of number average molecular weight 6090+/-90 showed extensive surface erosion and superficial fragmentation that was surrounded by a number of inflammatory cells, while OPF hydrogels with PEG block length of number average molecular weight 930+/-10 elicited minimal degradation. Constant fibrous capsule layers and number of inflammatory cells were observed regardless of the incorporation of cell-binding peptide and crosslinking density of OPF hydrogels with PEG block length of number average molecular weight 930+/-90. These results confirm that the degradation of implants can be controlled by tailoring the macromolecular structure of OPF hydrogels. Additionally, histological evaluation of implants proved that the OPF hydrogel is a promising material for biodegradable scaffolds in tissue engineering.

Animals↗

PubMed2005

pH-sensitive behavior of two-component hydrogels composed of N,O-carboxymethyl chitosan and alginate.

A two-component pH-sensitive hydrogel system composed of a water-soluble chitosan derivative (N,O-carboxymethyl chitosan, NOCC) and alginate cross-linked by genipin, glutaraldehyde or Ca2+ was investigated. Preparation and structures of these hydrogels and their swelling characteristics and release profiles of a model protein drug (bovine serum albumin, BSA) in simulated gastrointestinal media are reported. At pH 1.2, the swelling ratios of the hydrogels cross-linked by distinct methods were limited. Of note is that the lowest swelling ratios of test hydrogels were found at pH 4.0. At pH 7.4, the carboxylic acid groups on test hydrogels became progressively ionized and led to a significant swelling. There was barely any BSA released from the glutaraldehyde-cross-linked hydrogel throughout the entire course of the study. The amounts of BSA released at pH 1.2 from the genipin- and Ca(2+)-cross-linked hydrogels were relatively low (approx. 20%). At pH 4.0, there was still significant BSA release from the Ca(2+)-cross-linked hydrogel, while the cumulative BSA released from the genipin-cross-linked hydrogel was limited due to its shrinking behavior. At pH 7.4, the amount of BSA released from the genipin- and Ca(2+)-cross-linked hydrogels increased significantly (approx. 80%) because the swelling of both test hydrogels increased considerably. The aforementioned results indicated that the swelling behaviors and drug-release profiles of these test hydrogels are significantly different due to their distinct cross-linking structures.

Alginates↗

PubMed2002

Modulation of marrow stromal osteoblast adhesion on biomimetic oligo[poly(ethylene glycol) fumarate] hydrogels modified with Arg-Gly-Asp peptides and a poly(ethyleneglycol) spacer.

Novel oligo[poly(ethylene glycol) fumarate] (OPF) hydrogels functionalized with cell adhesion peptides were prepared, and the effects of incorporated peptide density and macromolecular structure of hydrogels on attachment and morphology of marrow stromal cells (MSCs) were evaluated. Poly(ethylene glycol) (PEG; number average molecular weight of 930, 2860, and 6090) was used to synthesize OPF. A model peptide, Gly-Arg-Gly-Asp (GRGD), was incorporated into OPF hydrogels after being coupled to acrylated PEG of molecular weight 3400. The increase of incorporated peptide concentration enhanced MSC attachment to OPF hydrogels of PEG of molecular weight of 930 and 2860. However, the number of attached MSCs to OPF hydrogels of PEG (molecular weight 6090) remained constant regardless of the peptide density. The length of PEG in OPF also influenced cell attachment. When 1 micromole peptide/g hydrogel was incorporated into the OPF hydrogels, the degree of cell attachment at 12 h relative to the initial seeding density was 93.9 +/- 5.9%, 64.7 +/- 8.2%, and 9.3 +/- 6.6% for OPF hydrogels prepared with PEG of molecular weights of 930, 2860, and 6090, respectively. However, the crosslinking density of hydrogels did not significantly affect cell attachment. The interaction was sequence specific, in that MSC attachment to GRGD-modified hydrogels was competitively inhibited when cells were incubated in the presence of 0.5 mM soluble GRGD before cell seeding. These results suggest that we can modulate MSC attachment to OPF hydrogels by altering the peptide density and the molecular structure of OPF hydrogels.

Animals↗

PubMed2003

Three-dimensional culture of differentiating marrow stromal osteoblasts in biomimetic poly(propylene fumarate-co-ethylene glycol)-based macroporous hydrogels.

This study assesses the ability of biomimetic poly(propylene fumarate-co-ethylene glycol)-based hydrogels to sustain the differentiation of marrow stromal cells (MSCs) to the osteoblastic phenotype and to produce a mineralized matrix in vitro. Macroporous hydrogels based on poly(propylene fumarate-co-ethylene glycol) with and without covalently linked RGD cell-adhesive peptide were synthesized and seeded with rat MSCs suspended in media or in a type I collagen solution. Cells suspended in media were found to adhere to RGD-modified but not to unmodified hydrogels. Cells suspended in a collagen solution were entrapped after collagen gelation and proliferated independent of the peptide modification of the hydrogel. Hydrogel modification with RGD peptide was sufficient to allow for the adhesion and differentiation of MSCs to the osteoblastic phenotype in the presence of osteogenic culture supplements. MSCs seeded with a collagen gel onto RGD-modified macroporous hydrogels after 28 days of culture showed a significant increase in cell numbers, from 15,200 +/- 2,000 to 208,600 +/- 69,700 cells (p < 0.05). Moreover, significant calcium deposition was apparent after 28 days of culture in RGD-modified hydrogels for cells suspended in a collagen gel in comparison to cells suspended in media, 3.47 +/- 0.26 compared to 0.82 +/- 0.20 mg Ca(2+) per scaffold (p < 0.05). Confocal microscopy revealed that MSCs suspended in a collagen gel and cultured on RGD-modified hydrogels for 28 days were adhered to the surface of the hydrogel while MSCs suspended in a collagen gel and cultured on unmodified hydrogels were located within the pores of and not in direct contact with the hydrogel surface. The results demonstrate that these biomimetic hydrogels facilitate the adhesion and support the differentiation of MSCs to the osteoblastic phenotype in the presence of osteogenic culture media.

Alkaline Phosphatase↗

PubMed2002

A 1-year prospective clinical trial of balafilcon a (PureVision) silicone-hydrogel contact lenses used on a 30-day continuous wear schedule.

PURPOSE: To evaluate silicone-hydrogel balafilcon A (PureVision, Bausch & Lomb Inc., Rochester, NY) contact lenses worn on a 30-day continuous wear basis when compared with a traditional hydrogel (Acuvue, Vistakon, Johnson and Johnson Vision Products, Inc., Jacksonville, FL) worn on a 7-day extended wear schedule. DESIGN: Prospective, comparative, paired-eye, interventional, multicenter clinical trial. PARTICIPANTS: Two hundred twelve ametropes with no significant ocular pathology. METHODS: Subjects with normal ocular health who conformed to a set of standard criteria were monitored at seven different sites around the globe. Subjects wore both study lenses simultaneously, one on each eye. Lenses were assigned to right and left eyes according to a randomized schedule. The silicone hydrogel was removed and replaced every month and the traditional hydrogel was removed every 7 days and replaced at 14-day intervals. Subjects were followed for up to 1 year with discontinuation on indication divided between lens-related causes, unrelated factors, and loss to follow-up. MAIN OUTCOME MEASURES: Discontinuations, symptoms, vision, lens fit, lens surface assessment, slit-lamp assessment, and patient preferences. RESULTS: One hundred twenty three subjects completed the 12-month wearing period. There were no vision-threatening events with either lens type. The silicone-hydrogel lenses showed statistically superior performance in physiologic terms with regard to epithelial microcysts, striae, corneal staining, limbal injection, and bulbar injection. Inflammatory reactions, such as corneal infiltrates and tarsal conjunctival abnormalities occurred at similar rates between the lens types. Visible deposition and postlens debris with associated transient corneal indentation were significantly lower with the traditional hydrogel material at specific time points in the study. Visual acuity was comparable with the two lens types. Subjects rated the silicone-hydrogel material as preferable on subjective scales of dryness, comfort, and lens handling. Overall subjective performance was rated superior with the silicone-hydrogel material. CONCLUSIONS: The high oxygen performance of the silicone-hydrogel lenses provides a superior physiologic environment compared with a traditional hydrogel material during continuous wear. Despite the slightly higher levels of visible deposit on the silicone-hydrogels, superior subjective responses suggest that the plasma coating technology on these lenses is effective in providing comfortable lens wear. The results look promising for the success of silicone-hydrogels as the material of choice for continuous wear contact lenses.

Adolescent↗

PubMed2001

Controlled release of clot-dissolving tissue-type plasminogen activator from a poly(L-glutamic acid) semi-interpenetrating polymer network hydrogel.

With the aim of developing an effective therapeutic modality for treatment of thrombosis, a tissue-type plasminogen activator (t-PA)-loaded porous poly(L-glutamic acid) (PLGA) semi-interpenetrating polymer network (semi-IPN) hydrogel was developed as a possible local drug delivery system. Porous structure of hydrogel was essential in this system to yield a large surface area so that t-PA release could be facilitated. This semi-IPN hydrogel was prepared using the method of free-radical polymerization and crosslinking of polyethylene glycol (PEG)-methacrylate through the PLGA network. Sodium bicarbonate (NaHCO(3)) was added to function as a foaming agent under acidic conditions, rendering the semi-IPN hydrogel to be porous. While the added NaHCO(3) provided gas foam in the reaction mixture, the pH in the hydrogel increased to about 7 to 8, which stimulated the polymerization. The porous structure that was presented at both the surface and sublayer was stabilized during hydrogel formation and freeze-drying. The hydrogel thus prepared possessed a porous structure of 10-20 microm in diameter, as determined by scanning electron microscopy. Results showed that the above hydrogel preparation process did not significantly alter the specific activity of the entrapped t-PA with regard to plasminogen activation and fibrin clot lysis ability. The t-PA release from this semi-IPN hydrogel was examined by measuring the plasmin activity using the chromogenic substrate S-2251. Findings in this paper demonstrated that the porous structure of the hydrogel facilitated t-PA release when compared to the dense structure. Aside from the porous structure, other factors including the content of the crosslinker, PLGA and t-PA could all be varied to regulate t-PA release from the hydrogel. These results suggest that a porous PLGA semi-IPN hydrogel could potentially be a useful local delivery system to release active t-PA primarily at the site of a thrombus.

Blood Coagulation↗

PubMedDate not supplied

Characterization of the spontaneously forming hydrogels composed of water-soluble phospholipid polymers.

Spontaneously forming hydrogels composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers, poly(MPC-co-methacrylic acid) (PMA), and poly(MPC-co-n-butyl methacrylate) (PMB) were examined. The MPC copolymer hydrogel was observed to have a spontaneous gelation property. To determine the properties of the hydrogels and why the gelation takes place, we have studied the properties of the hydrogels by scanning electron microscopy, X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC). The morphologies of the hydrogels were spongelike with a homogeneous structure. By XPS analysis in terms of the molecular distributions in the hydrogels, it was observed that a stabilization time was required for the hydrogel to undergo chain rearrangement. DSC thermograms of the hydrogels were different from their components, PMA and PMB. For the hydrogel, a crystallization peak around -30 degrees C was observed. This result indicated that some ordered structures existed in the hydrogels. To determine the role of the MPC groups, aqueous solutions of poly(methacrylic acid) (PMAc) and PMB were mixed. The mixture of PMAc-PMB turned into a sol state, and the sol state remained for a week. When the mixture was cooled, a very weak hydrogel was prepared. This result suggested that the MPC groups were the dominant unit for spontaneously forming the hydrogels.

Biocompatible Materials↗

PubMed2006

Continuous glucose sensing with fluorescent thin-film hydrogels. 2. Fiber optic sensor fabrication and in vitro testing.

BACKGROUND: There continues to be a need for better sensors for continuous glucose monitoring. We are working on a two-component sensing system based on a viologen boronic acid and a fluorescent dye, which are immobilized in a hydrogel. This system has the potential for further development into a real-time glucose-monitoring device. The current study reports the fabrication of sensors using preformed hydrogels and the first in vitro monitoring of glucose concentrations in a prototype sensor configuration. METHODS: Glucose sensing hydrogels containing a fluorescent dye and viologen boronic acid quencher were preformed in a mold. These preformed hydrogels were then attached to the distal end of a plastic fiber optic cable using different adhesives to prepare the in vitro sensors. These sensors were connected to a flow cell and monitored using a fluorescence spectrometer. The fluorescence emitted by the hydrogel changes depending on the glucose concentration. Hydrogel components were modified in order to optimize the performance of the sensors. RESULTS: A soft tissue adhesive used by veterinarians was found to be an effective adhesive for bonding the hydrogel to the fiber tip. This adhesive did not affect the glucose sensing ability of the hydrogels after fabrication. Several sensors were fabricated with varying composition of sensing elements, and all of them showed stable and reversible glucose response. The glucose signal was found to be stable over months on repeated testing. Glucose sensing studies using the sensors with hydrogels containing different compositions of sensing elements showed that the ratio of dye to quencher is an important parameter in determining the magnitude and linearity of glucose response in the biological range. The response time of the sensor was shown to be dependent on the hydrophilicity of the hydrogels. Modifying the hydrogels with ionic comonomers shortened the response time. CONCLUSIONS: The combination of the anionic dye 2 and viologen-based boronic acid 1 immobilized in a 2-hydroxyethyl methacrylate hydrogel functions well in a fiber optic configuration. This preliminary study suggests that the two-component sensing system has several advantages in terms of stability and ease of fabrication. Improvement of the configuration of the sensor and further development of the sensor towards application for in vitro study are underway.

Drug Monitoring↗

PubMed2001

Controlled release of growth factors based on biodegradation of gelatin hydrogel.

To develop a carrier for the controlled release of biologically-active growth factors, biodegradable hydrogels were prepared through glutaraldehyde cross-linking of gelatin with isoelectric points (IEP) of 5.0 and 9.0, i.e. 'acidic' and 'basic' gelatins, respectively. Radioiodinated growth factors were used to investigate their sorption and desorption from the hydrogel of both types of gelatin. Basic fibroblast growth factor (bFGF) and transforming growth factor-beta1 (TGF-beta1) were well sorbed with time to the acidic gelatin hydrogel, while less sorption was observed for the basic gelatin hydrogel. This could be explained in terms of the electrostatic interaction between the growth factors and the acidic gelatin. However, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), though their IEPs are higher than 7.0, were sorbed to the acidic gelatin hydrogel to a smaller extent than the two other growth factors. Under in vitro non-degradation conditions, approximately 20% of the incorporated bFGF and TGF-beta1 was desorbed from the hydrogels within the initial 40 min, followed by no further substantial desorption, whereas large initial desorption was observed for BMP-2 and VEGF. When implanted in the back subcutis of mice, gelatin hydrogels were degraded over time. Each growth factor was retained in vivo being incorporated in the acidic gelatin hydrogel: the smaller the in vitro desorption amount from the hydrogel, the longer the in vivo retention time. The in vivo profile of bFGF and TGF-beta1 retention was in good accordance with that of the hydrogel. These findings indicate that the growth factor immobilized to the acidic gelatin hydrogel through ionic interaction was released in vivo as a result of hydrogel degradation.

Adsorption↗

PubMed2006

Hydrogel meniscal replacement in the sheep knee: preliminary evaluation of chondroprotective effects.

BACKGROUND: Meniscal allograft transplantation has become a viable surgical alternative for a select group of patients with deficient or irreparable menisci. Subjective results are encouraging; long-term success, durability, and safety of allograft meniscal transplantation are uncertain. PURPOSES: To evaluate a novel hydrogel meniscal replacement implant in an ovine model and assess chondroprotective effects of this hydrogel meniscal replacement using several validated outcome measures. STUDY DESIGN: Controlled laboratory study. METHODS: Fourteen skeletally mature sheep underwent hydrogel meniscal replacement; 45 additional animals had previously undergone 1 of 3 operations: lateral meniscectomy (24), meniscal allograft transplant (17), and sham (4). Animals were sacrificed at 2, 4, or 12 months. Cartilage was assessed by magnetic resonance imaging, gross inspection, biomechanical testing, and semiquantitative histological analysis. RESULTS: There were no differences between the sham operation and nonoperated control limbs. Compared with meniscectomy, hydrogel meniscal replacement resulted in significantly decreased cartilage degeneration with all outcome parameters (P < .05). Compared with nonoperated control limbs, hydrogel meniscal replacements demonstrated no significant differences at 2 months in any category. By 4 months, hydrogel limbs demonstrated significantly greater cartilage degeneration than did nonoperated control limbs in all categories. Compared with meniscal allograft transplantation animals, hydrogel meniscal replacements demonstrated no differences at 2 months but had significantly increased cartilage degeneration in the peripheral zone of the tibial plateau at 4 months (P < .05). At 1 year, all hydrogel implants had developed complete radial splits in the posterior third of the implant. CONCLUSION: Although promising preliminary results for hydrogel meniscal replacement were seen at early time points, significant cartilage degeneration and implant failure were seen at 1 year, and overall performance was worse than was allograft transplantation. Improvements in hydrogel material properties and surface characteristics and more accurate size matching may improve outcomes. CLINICAL RELEVANCE: Improvements in the hydrogel material properties and surface characteristics and more accurate size matching may lead to the use of hydrogel implants in humans.

Analysis of Variance↗

PubMed2001

Preparation and characterization of insulin-loaded acrylic hydrogels containing absorption enhancers.

The objectives of this study were to prepare insulin-loaded acrylic hydrogel formulations containing various absorption enhancers, to perform in vitro and in vivo characterization of these formulations, and to evaluate the factors which affecting insulin availability on rectal delivery of insulin using this hydrogel system. The acrylic block copolymer of methacrylic acid and methacrylate, Eudispert, was used to make the hydrogel formulations. As absorption enhancers, 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD), lauric acid (C12), or the sodium salt of C12 (C12Na), were incorporated into the hydrogels. In an in vitro release test, the release rate of insulin from the hydrogels decreased as the polymer concentration of the hydrogel increased. The addition of C12Na to the hydrogel further increased the insulin release rate, which was greater at higher concentrations of the enhancer. A portion of the C12Na was found to remain bound to the acrylic polymer in dissolution medium. Serum insulin levels were determined at various time points after the administration of insulin solution or insulin-loaded (50 units/kg body weight) Eudispert hydrogels containing 5% (w/w) of C12, C12Na, or DM-beta-CyD to in situ loops in various regions of the rat intestine. The most effective enhancement of insulin release was observed with formulations containing C12Na. The bioavailability of insulin from the hydrogels was lower than that from the insulin solutions. Hydrogel formulations containing 7% or 10% Eudispert remained in the rectum for 5 h after rectal administration. However, the 5% (w/w) C12Na solution stained with Evan's-blue had diffused out and the dye had reached the upper intestinal tract within 2 h. Finally, the rectal administration of insulin-loaded hydrogels, containing 4%, 7%, or 10% (w/w) Eudispert and 5% (w/w) of enhancer (C12, C12Na, or DM-beta-CyD) to normal rats was shown to decrease serum glucose concentrations. The greatest effect was found with insulin-loaded 7% (Eudispert) hydrogel containing C12Na which having cosiderable large insulin release rate and bioadhesive characteristics.

Acrylates↗

PubMed2005

Drug release from hydrogel containing albumin as crosslinker.

Albumin is the major plasma protein and acts as a physiological carrier for various compounds including drugs. To take advantage of the drug-binding ability of albumin for a drug delivery system, we have prepared hydrogels consisting of acrylamide (AAm) and bovine serum albumin (BSA) by introducing three to four vinyl groups into one BSA molecule and subsequently copolymerizing it with AAm. The resultant hydrogel was solubilized by trypsin treatment, since BSA served as a crosslinker in the hydrogel. The BSA-crosslinked hydrogel (BSA-AAm hydrogel) was loaded with salicylic acid or sodium benzoate and their release was investigated. The BSA-AAm hydrogel released much more salicylic acid than sodium benzoate. In addition, the amount of released salicylic acid increased with the BSA content of the hydrogel, despite a decrease in the swelling ratio of the hydrogel. On the other hand, the amount of released sodium benzoate increased with the swelling ratio. When a hydrogel crosslinked with N,N'-methylenebis (acrylamide) was used as a control, both drugs showed release tendencies similar to that of sodium benzoate from the BSA-AAm hydrogel. Furthermore, the salicylic acid release was sustained longer on the BSA-AAm hydrogel than the sodium benzoate release. Taken together, it is thought that albumin in the BSA-AAm hydrogel preferentially adsorbs salicylic acid and contributes to the high drug loading and the sustained release of salicylic acid.

Acrylamide↗

PubMed2005

Attachment of Acanthamoeba to first- and second-generation silicone hydrogel contact lenses.

PURPOSE: To investigate the attachment of Acanthamoeba to first- and second-generation silicone hydrogel contact lenses, and to determine if patient wear or the presence of a bacterial biofilm coating affects attachment characteristics. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Attachment to the silicone hydrogel lenses was compared with that to a conventional hydrogel control lens. Sixteen replicates (n = 16) were carried out for unworn, worn, and biofilm-coated lenses of each type. METHODS: Unworn, worn, and Pseudomonas aeruginosa biofilm-coated first-generation (lotrafilcon A) and second-generation (galyfilcon A) silicone hydrogel and conventional hydrogel (etafilcon A) lens quarters were incubated for 90 minutes in suspensions of plate-cultured Acanthamoeba castellanii trophozoites. MAIN OUTCOME MEASURES: Trophozoites attached to one surface of each lens quarter were counted by direct light microscopy. Logarithmic transformation of data allowed the use of parametric analysis of variance for statistical analysis. RESULTS: Attachment of Acanthamoeba was affected significantly by lens material type (P<0.001), with higher numbers of trophozoites attaching to the first-generation lotrafilcon A silicone hydrogel lens, compared with the second-generation galyfilcon A lens and the conventional hydrogel lens. Attachments to the latter 2 lenses did not differ significantly from each other (P = 0.126). Patient wear and the presence of a bacterial biofilm had no significant effect on attachment to the lotrafilcon A lens (P = 0.426) but did significantly increase attachment to the galyfilcon A (P<0.001) and the etafilcon A (P = 0.009) lenses; attachment to the latter 2 lenses was still significantly less than that found with the first-generation silicone hydrogel (P<0.001). CONCLUSIONS: Acanthamoeba demonstrated a significantly greater affinity for the first-generation silicone hydrogel lens as compared with the second-generation silicone hydrogel and the conventional hydrogel. If exposed to Acanthamoeba (e.g., when showering or swimming, through noncontinuous wear and ineffective lens care regimes), first-generation silicone hydrogel lenses may promote a greater risk of Acanthamoeba infection due to the enhanced attachment characteristics of this lens material. However, prospective studies in patients are required to determine if these experimental results are clinically significant.

Acanthamoeba castellanii↗