Hydrogel Barrier Research Articles

Biomaterial testing for covered stent membranes: Evaluating thrombosis and restenosis potential

Covered stents may be able to prevent both thrombosis and restenosis, but new mechanically suitable and biocompatible materials are needed before this treatment option can become a reality. Hydrophilic polyvinyl alcohol (PVA) cryogels have desirable mechanical properties for covered stent membranes and may be able to provide a physical barrier to restenosis with low thrombogenicity. An in vitro flow loop with porcine blood was used to compare thrombus formation on different blood-contacting biomaterials. PVA cryogels were found to maintain blood flow with low thrombogenicity and were significantly less thrombogenic than polyester (p < 0.05). The ability to prevent hyperplasic in-growth was evaluated using a modified Boyden chamber cellular migration assay. PVA cryogel membranes used as a physical barrier were found to nearly eliminate cellular migration (p < 0.05) without cellular toxicity. Overall, this article demonstrates pivotal feasibility results for a covered stent membrane material that could prevent restenosis by means of a hydrogel barrier with low thrombogenicity.

Reduction of postsurgical adhesion formation with CM‐chitosan hydrogel barriers prepared by using γ‐irradiation

AbstractTo evaluate the efficiency of carboxymethylchitosan (CM‐chitosan)‐based hydrogels as barriers for reducing postsurgical adhesions, CM‐chitosan was synthesized to simplify the hydrogel‐making process, and the CM‐chitosan solutions were cross‐linked by using γ‐ray irradiation to create the desired hydrogels instead of using chemical cross‐linking reagents. The prepared CM‐chitosan hydrogels were characterized by a FTIR spectroscopy, swelling behavior, gel‐fraction content,and mechanical property such as gel strength of a hydrogel and the results showed a good swelling behavior and mechanical properties. Also, the radiation‐induced CM‐chitosan hydrogels significantly reduced and inhibited the postsurgical adhesions in the rat models. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions' prevention

Post-operative peritoneal adhesions are common and serious complications for surgeons. They can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We synthesized injectable hydrogels that formed by chemical modification through grafted hydrobutyl groups to chitosan chains. Gelation of hydroxybutyl chitosan (HBC) occurs in less than 60 s. Once formed, it can also be recovered completely. The residue time of hydrogels can extend to 4 weeks in Kunming mice. HBC hydrogels showed mild cytotoxicity to mice fibroblast cell (L929) and human vascular endothelial cell (ECV-304) in vitro and were biocompatible in the murine muscles, causing no adhesions for 4 weeks. HBC gels can form a durable barrier between defected cecum and abdominal wall. In a mice sidewall defect-bowel abrasion model, HBC gels showed significant efficacy in reducing adhesion formation.

UV-cured poly(vinyl alcohol) ultrafiltration nanofibrous membrane based on electrospun nanofiber scaffolds

A novel class of high-flux thin film nanofibrous composite (TFNC) ultrafiltration membrane, consisting of UV-cured poly(vinyl alcohol) (PVA) hydro-gel barrier layer, electrospun nanofibrous PVA mid-layer scaffold and polyethylene terephthalate (PET) non-woven substrate, was investigated. The barrier layer was fabricated by photo-crosslinking of UV-reactive PVA (UV-PVA) on a chemically cross-linked nanofibrous PVA scaffold. The effects of concentration and viscosity of the UV-PVA solution on the flux and rejection rate of the TFNC membrane were studied. It was found that UV curing of a 5-wt% UV-PVA solution coating over 20-s time period yielded a high flux, high rejection UF membrane with good fouling resistance for separation of oil and water emulsion.

Effects of PEG hydrogel crosslinking density on protein diffusion and encapsulated islet survival and function

The rational design of immunoprotective hydrogel barriers for transplanting insulin-producing cells requires an understanding of protein diffusion within the hydrogel network and how alterations to the network structure affect protein diffusion. Hydrogels of varying crosslinking density were formed via the chain polymerization of dimethacrylated PEG macromers of varying molecular weight, and the diffusion of six model proteins with molecular weights ranging from 5700 to 67,000 g/mol was observed in these hydrogel networks. Protein release profiles were used to estimate diffusion coefficients for each protein/gel system that exhibited Fickian diffusion. Diffusion coefficients were on the order of 10(-6)-10(-7) cm(2)/s, such that protein diffusion time scales (t(d) = L(2)/D) from 0.5-mm thick gels vary from 5 min to 24 h. Adult murine islets were encapsulated in PEG hydrogels of varying crosslinking density, and islet survival and insulin release was maintained after two weeks of culture in each gel condition. While the total insulin released during a 1 h glucose stimulation period was the same from islets in each sample, increasing hydrogel crosslinking density contributed to delays in insulin release from hydrogel samples within the 1 h stimulation period.

Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide

Peritoneal adhesions are tissue connections that form within the abdominopelvic cavity following surgery or other injuries. They can cause major medical complications. Barrier devices and pharmacological agents have been used to prevent adhesion formation, with mixed success. We hypothesize that an adhesion barrier which also delivers anti-adhesion drugs can address both physical and physiological causes for adhesion formation. Here, we describe an in situ cross-linking hyaluronan hydrogel (barrier device) containing the glucocorticoid receptor agonist budesonide. Budesonide was chosen because of the known role of inflammation in adhesion formation, hyaluronan because of its known biocompatibility in the peritoneum. The system, consisting of two cross-linkable precursor liquids, was applied using a double-barreled syringe, forming a flexible and durable hydrogel in less than 5 s. We applied this formulation or controls to the injured sites after the second injury in a severe repeat sidewall defect–cecum abrasion model of peritoneal adhesion formation in the rabbit. Large adhesions (median area 15.4 cm 2) developed in all saline-treated animals. Adhesion formation and area were slightly mitigated in animals treated with budesonide in saline (median area 5.0 cm 2) or the hydrogel without budesonide (median area 4.9 cm 2). The incidence and area of adhesions were dramatically reduced in animals treated with budesonide in the hydrogel (median area 0.0 cm 2). In subcutaneous injections in rats, budesonide in hydrogel reduced inflammation compared to hydrogel alone. In summary, budesonide in a hyaluronan hydrogel is easy to use and highly effective in preventing adhesions in our severe repeated injury model. It is a potentially promising system for post-surgical adhesion prevention, and suggests that the effectiveness of barrier devices can be greatly enhanced by concurrent drug delivery.

A miniaturized electrochemical system with a novel polyelectrolyte reference electrode and its application to thin layer electroanalysis

Miniaturized liquid junction reference electrodes with short- and long-term stabilities were fabricated by using photopolymerization of a patterned polyelectrolytic hydrogel, poly diallyldimethylammonium chloride (pDADMAC). Internal and external solutions were separated by the polyelectrolytic hydrogel barrier, through which Cl− ions carried the ionic current. The impedance spectrum of the developed hydrogel-based salt bridge was flat at 40kΩ, indicating negligible capacitance. Most of thin film-type reference electrodes patterned on microfluidic chips suffer from a short lifespan and complicated structure, which seriously antagonize the advantages of electrochemical detection. The novel reference electrode system using a polyelectrolyte salt bridge on a microfluidic chip maintained a reproducible potential of 19.3±6mV versus a commercial Ag/AgCl reference electrode over 30h. Anionic interferents such as Br−, I−, and S2− ions had no influence on the performance of the reference electrode. In particular, the dependence on the Cl− ion concentration was substantially suppressed by separating the Ag/AgCl wire from the sample solution with the salt bridge. A 10μm-thick cell with a polyelectrolyte salt bridge on a microfluidic chip showed the typical voltammetric behavior of thin layer cells that was confirmed by cyclic voltammetry (CV). This chip-based thin layer cell was exploited to determine the concentration of dopamine by differential pulse voltammetry (DPV) as well. A linear current response was observed down to 5μM dopamine and the limit of detection was calculated to 2μM.

Magnetic Resonance Imaging Analysis of Moving Fronts in Floating Dosage Forms

Floating systems could be useful for controlled delivery of drugs which act locally in the stomach or have a narrow absorption window in the proximal part of the gastrointestinal tract. Among the floating systems hydrodynamically balanced systems (HBS) are the only commercially available formulations. HBS are essentially composed of a drug intimately mixed with gel forming hydrocolloids, which swell in contact with gastric fluid. The hydrogel shell maintains a relative integrity of shape and has a bulk density smaller than 1 g/cm. The drug is slowly released in the stomach by diffusion through the hydrogel barrier and erosion of the surface of the dosage form. ∗corresponding author

Bioencapsulation by compression coating of probiotic bacteria for their protection in an acidic medium

Compression coating was demonstrated as a novel encapsulation method for improving cell survival when cells were exposed to an acidic medium. Sodium alginate, which can form gels after being hydrated, has been exploited as the prime coating material. Probiotic cell containing powders were first compressed into a pellet, which was then encapsulated with the coating material by further compression. Results indicated significant improvement in survival of encapsulated cells when exposed to acidic media of pH 1.2 and 2. The encapsulated cells showed 10 4–10 5-fold increment in cell survival when compared to free cells under the test conditions. The formation of a hydrogel barrier by the compacted sodium alginate layer has shown to retard the permeation of the acidic fluid into the cells. This contributed to the enhanced cell survival. In addition, it could be deduced from in vitro tests that the release of encapsulated cells in the human digestive tract could occur near the end of the ileum and beginning of the colon. The mechanism of cell release is primarily due to the erosion of the alginate gel layer.

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

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. 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. 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. 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.

Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: the roles of medial and luminal factors in arterial healing.

The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20-microns thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF.

Adhesion Prevention with Ancrod Released via a Tissue-Adherent Hydrogel

The objective of this investigation was to evaluate the effect of ancrod, a fibrinogenolytic protease from Malayan pit viper venom, locally delivered through a photopolymerized biodegradable hydrogel in preventing postoperative adhesions. The experimental model involved ischemic and serosal injury to the uterine horns of rats with measurement of adhesions 7 days after injury. Ancrod was delivered intravenously for 5 days preoperatively through 3 days postoperatively, intraperitoneally for 5 days preoperatively, intraperitoneally for 3 days postoperatively, and locally via the hydrogel formed upon the uterine horns by photopolymerization of an aqueous precursor solution. Systemic defibrinogenation by intravenous administration pre- through postoperatively reduced the extent of adhesions by 63% without dose sensitivity from 5 to 20 units/kg/day. Preoperative defibrinogenation by intraperitoneal administration reduced adhesion extent by up to 57%, while postoperative administration was more effective, reducing adhesions by up to 84% with a dose-dependent response from 5 to 20 units/kg/day. Administration of ancrod by local release from a tissue-adherent hydrogel was more effective than either the hydrogel alone or the same amount of ancrod administered by postoperative intraperitoneal injection. Adhesions were reduced by 82% at a local dose of 10 units/kg, compared to a reduction of 68% due to the barrier properties of the gel alone (P< 0.01) and of 19% due to the same amount of drug given at the time of surgery (P< 0.001). Local delivery of ancrod from a tissue-adherent hydrogel barrier thus provided an efficacious prevention to postoperative adhesions while permitting administration of a low total dose of the protease.

Characterization of the formation of interfacially photopolymerized thin hydrogels in contact with arterial tissue

The aim of this study was to examine the conditions under which an interfacial photopolymerization process results in hydrogel barriers. Visible light initiated interfacial photopolymerization of a polyoxyethylene glycol (PEG)-co-poly(α-hydroxy acid) copolymer based on PEG 8000 macromonomer was performed on porcine aortic tissue, resulting in conformai hydrogel barriers. The process conditions were optimized in vitro for the formation of a 5–100 μm thick barrier.

Efficacy of a resorbable hydrogel barrier, oxidized regenerated cellulose, and hyaluronic acid in the prevention of ovarian adhesions in a rabbit model

To compare the efficacy of a resorbable hydrogel material with oxidized regenerated cellulose and hyaluronic acid in an ovarian adhesion model. Controlled, blinded, and randomized study involving female rabbits. Academic research environment. A water-soluble hydrogen precursor was applied to the ovary as a liquid and converted to a hydrogel by exposure to long wavelength ultraviolet light, a 0.4% solution of hyaluronic acid was applied to the ovary, or an oxidized regenerated cellulose patch was applied to the ovary after wedge resectioning. Extent and severity of adhesion formation. Application of the hydrogel reduced adhesion formation by 88%. Neither oxidized regenerated cellulose nor hyaluronic acid reduced adhesion formation. The photopolymerized, resorbable hydrogel material is highly effective for the reduction of periovarian adhesions in this model.

Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention.

The aim of this study was to optimize the properties of a lubricious bioerodible hydrogel barrier for the prevention of postoperative adhesions. Water-soluble macromers based on block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) or poly(glycolic acid) with terminal acrylate groups were used, and these macromers were gelled in vivo by exposure to long wavelength ultraviolet light. The precursor was photopolymerized from buffered saline solution while in contact with the tissues. This resulted in the conformal coating of the tissue with an adherent hydrogel film, while forming a nonadhesive barrier at the free surface, on the treated wound site. The hydrogels were evaluated in two animal models of postsurgical adhesions, first in a rat cecum abrasion model and then in a rabbit uterine horn ischemia model. In the rat cecum model, six of seven animals treated with a hydrogel, with glycolide in the precursor as the comonomer, showed no adhesions; untreated animals and animals treated with precursor, but not gelled with light, showed consistent dense adhesions. In the rabbit uterine horn ischemia model, using hydrogels with lactide in the precursor as the comonomer, and PEG of molecular weight from 6,000 to 18,500 Da, adhesions were dramatically reduced, with occurrence in none of seven animals treated with a gel containing PEG 10,000. By contrast, the seven animals in the control group demonstrated a mean of 35% involvement of the horn length in dense, fibrous adhesions. These materials, photopolymerized in vivo in direct contact with the tissues, appear to form an adherent hydrogel barrier that is highly effective in reducing postoperative adhesions in the models used.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers.

Thin hydrogel barriers formed on the inner surface of injured arteries by interfacial photopolymerization dramatically reduced thrombosis and intimal thickening in rat and rabbit models of vascular injury. This polymerization technique allowed the synthesis of a thin hydrogel barrier that conformed to the vessel wall, directly blocking contact between blood and the damaged vessel. The illumination conditions could be varied to control the thickness of the barrier from 10 microns to > 50 microns. The hydrogel was designed to degrade by nonenzymatic hydrolysis. In rats in which the carotid artery had been severely injured by crushing, treatment with the hydrogel barrier completely eliminated thrombosis (P < 0.01) and preserved long-term patency (P < 0.01). Treatment in a rabbit model of balloon injury inhibited thrombosis (P < 0.02) and reduced long-term intimal thickening by approximately 80% (P < 0.003). These results suggest that blood-borne signals acting in the early phases of healing play an important role in stimulating thickening of the intima.