Efficacy of adhesion barriers. Resorbable hydrogel, oxidized regenerated cellulose and hyaluronic acid.

OBJECTIVE: To compare a novel resorbable hydrogel barrier with two previously studied barriers, oxidized regenerated cellulose and hyaluronic acid, for the prevention of postoperative adhesions. STUDY DESIGN: Two models were employed in the rat uterine horn, one of adhesion formation after devascularization and serosal injury and one of adhesion reformation after adhesiolysis RESULTS: In the devascularization model, hydrogel treatment reduced the mean extent of adhesion formation from 73% in the control group to 13% (P < .005). Hyaluronic acid pretreatment reduced the extent of adhesion formation to 44% (P < .05), while oxidized regenerated cellulose failed to reduce formation (P > .25). In the adhesiolysis model, treatment with the hydrogel reduced the mean extent of adhesion formation from 87% in the control group to 20% (P < .005). Neither the oxidized regenerated cellulose nor the hyaluronic acid treatments lowered the extent of adhesion formation from the control group (P > .25). The hydrogel barrier was observed to be resorbed over a five-day period and remained adherent to the tissue during resorption. CONCLUSION: Resorbable hydrogel barriers are highly effective in the reduction of adhesion formation and reformation in the rat. This probably due to the good biocompatibility and retention of these materials upon the site of application.

A new photopolymerizable blood vessel glue that seals human vessel anastomoses without augmenting thrombogenicity.

A new nonbiologic photopolymerizable glue, polyethyleneglycol 400 diacrylate, was studied with respect to its mechanical and biochemical interaction with human blood vessels. Using the human placental artery model, we tested the ability of polyethyleneglycol 400 diacrylate to prevent leakage of blood at the site of vascular anastomoses, which are made porous by the presence of tissue gaps and suture puncture sites. Fibrin glue is known to augment local vessel thrombogenicity through the presence of the coagulation enzyme thrombin. We tested the effect of externally applied polyethyleneglycol 400 diacrylate (which does not contain thrombin) on luminal thrombin activity and platelet deposition from flowing human blood. At a shear rate of 312 per second and a transmural pressure of 80 cm H2O, the leakage rate of saline from human placental artery anastomoses was 1.0 +/- 1.2 ml/min (n = 8). When the same anastomoses were then glued, 7 of 8 of the anastomoses leaked less than 0.05 ml/min (p < 0.05). Platelet deposition to human vessels was not influenced by the external application of polyethyleneglycol 400 diacrylate either on intact vessels (no polyethyleneglycol 400 diacrylate, 0.51 +/- 0.28 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.47 +/- 0.26 x 10(6) platelets/cm2; n = 7) or at anastomoses (no polyethyleneglycol 400 diacrylate, 0.69 +/- 0.36 x 10(6) platelets/cm2; with polyethyleneglycol 400 diacrylate, 0.53 +/- 0.33 x 10(6) platelets/cm2; n = 8), p > 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Photo-crosslinked copolymers of 2-hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors.

A copolymer containing 88% 2-hydroxyethyl methacrylate (HEMA), 9% poly(ethylene glycol) (MW 18.5 kDa) tetra-acrylate and 3% ethylene dimethacrylate was prepared and evaluated for use as a biocompatible interface between glucose biosensors and tissue in the rat. The glucose sensor utilizes glucose oxidase that is electrically 'wired' to a gold current collector by a reduction-oxidation polymer. Coatings of the copolymer were crosslinked in situ on the sensors using long wavelength ultraviolet light and 2,2-dimethoxy-2-phenyl-acetophenone as the initiator. The effect these films had on the current response to glucose was measured. Over a glucose concentration range of 0-30 mM, the average percentage decrease in response was 45 +/- 28% (mean +/- 95% confidence interval) at 37 degrees C for films that were about 0.1 mm thick, an acceptable value. Copolymer-treated and control electrodes were implanted in the intrascapular subcutaneous tissue of male Sprague-Dawley rats for three days. The explanted samples were evaluated using scanning electron microscopy. The control electrodes were highly encapsulated with fibrous material, while the copolymer-treated electrodes induced much less encapsulation. The results show this copolymer to be a candidate as a biocompatible coating for electrically wired oxidoreductase-based subcutaneous biosensors.

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)

Modification of islet of langerhans surfaces with immunoprotective poly(ethylene glycol) coatings via interfacial photopolymerization.

Poly(ethylene glycol) (PEG) has been used previously to alter immune interactions and systemic clearance of therapeutic proteins. We present herein chemical approaches for the conceptually similar treatment of therapeutic cells and tissues whereby immune and cell adhesive interactions may be reduced or interrupted, in the context of the transplantation of xenogeneic islets of Langerhans for the treatment of insulin-dependent diabetes mellitus. Visible-light-initiated interfacial photopolymerization of multifunctional PEG-based macromers was performed directly upon the surface of rat islets of Langerhans to produce conformal barrier hydrogel coatings with thickness of order 10 microm. The islets continued to be normal in ultrastructure and function as reflected by response to a glucose challenge in vitro.

Polyimide-polyethylene glycol block copolymers: synthesis, characterization, and initial evaluation as a biomaterial.

Block copolyimides with varying amounts of polyethylene glycol (PEG) were synthesized and characterized by copolymerization of diaminodiphenyl ether (DDE), amino terminated PEG, and benzophenone tetracarboxylic acid dianhydride (BTDA). Strong materials were obtained, with enhanced flexibility as compared to the parent DDE-BTDA polyimide homopolymer. Incorporation of PEG led to an increase in water absorption by these copolymers, and hydrophilicity was increased as reflected by a decrease in air-water-polymer contact angle. These materials supported less cell adhesion in vitro than the parent polyimide homopolymer. Short term in vivo evaluation of these copolymers showed reduced fibrous encapsulation than was observed in the absence of PEG.

Prevention of postoperative adhesions in the rat by in situ photopolymerization of bioresorbable hydrogel barriers.

OBJECTIVE: To assess the efficacy of a novel resorbable hydrogel barrier for preventing postoperative adhesions in animals. METHODS: A hydrogel barrier was formed in situ by photopolymerizing a solution of a macromolecular prepolymer in buffered saline using long-wavelength ultraviolet light. Two models in the rat were evaluated. In a primary adhesion model, devascularization and serosal injury were performed on the uterine horns using bipolar electrocautery. The prepolymer solution was applied to the horns and illuminated to form the barrier. On the seventh postoperative day, the fraction of the length of the horns involved in adhesions was scored, as was the quality of the adhesions. In a readhesion model, adhesions were formed as described and were surgically lysed on the seventh day, then were treated subsequently with the barrier and scored after 7 additional days. Each group in both models consisted of seven animals per treatment condition. Four prepolymer concentrations were examined in the primary adhesion model, and the optimal one was examined in the readhesion model. RESULTS: A conformal hydrogel barrier coating was formed upon in situ photopolymerization and adhered to the treated tissues. No residual hydrogel barrier was observed 7 days after application of the optimal gel concentrations. In the primary adhesion model, the mean fraction of the horns involved in adhesions was reduced significantly, from 76% in controls to 10% (P < .0001), and treatment with a 10% solution of prepolymer was determined to be optimal (P = .025). In the readhesion model, surgical lysis of adhesions alone did not reduce adhesions significantly (from 86% to 79%; P = .3), whereas lysis with barrier treatment did (79% to 28%; P = .002). CONCLUSIONS: In situ photopolymerization allowed the formation of adherent, conformal barriers, which demonstrated high efficacy in the prevention of adhesion formation and reformation in animals. This efficacy and ease of use warrant clinical evaluation.

Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon alginate-poly(l-lysine) microcapsules for enhanced biocompatibility.

The biocompatibility of microcapsules made by the co-acervation of alginate and poly(l-lysine) (PLL) was enhanced by coating the surface of these microcapsules with a poly(ethylene glycol) (PEG)-based hydrogel. The hydrogel was formed by an interfacial photopolymerization technique using visible light from an argon ion laser. The light absorbing chromophore, eosin Y, was immobilized on the microcapsule surface. This restricted the formation of the PEG hydrogel to the surface of the microcapsule. The presence of the PEG gel on the surface was confirmed by fluorescent dextran entrapment, by direct visualization after dissolution of the underlying membrane and by electron spectroscopy for chemical analysis. The biological response of such microcapsules was evaluated by intraperitoneal implantation in mice. The PEG-coated microcapsules were found to be less inflammatory and were seen not to elicit a fibrotic response, as was the case with alginate-PLL microcapsules.