Faculty Bibliography

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.

The surface and blood compatibility characteristics of Pellethane polyurethane blended with 1% or 5% (w/w) polytetramethylene oxide (PTMO) were evaluated. Analysis by X-ray photoelectron spectroscopy indicated that blending of PTMO caused an increased amount of amide wax, a processing agent present in Pellethane, to be expressed on the surface of the blended films in vacuo. Dynamic contact angle measurements in water, however, showed that PTMO was preferentially expressed on the blend film surfaces in water. The two lower molecular weight species, PTMO and amide wax, were thus capable of reorienting, depending on the environmental conditions. An in vitro assay of platelet adherence and thrombosis showed that polyurethane blended with 5% PTMO had about two-thirds fewer adherent platelets compared to unblended polyurethane and that a blend containing 1% PTMO was intermediate in platelet adherence. Measurements of albumin adsorption from binary solution with fibrinogen indicated that PTMO blends did not preferentially adsorb albumin compared to unblended polyurethane. (c) 1996 John Wiley & Sons, Inc.

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/METHODS: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/CONCLUSIONS: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.

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.

The mechanism of neurite penetration of three-dimensional fibrin matrices was investigated by culturing embryonic chick dorsal root ganglia (DRGs) within fibrin gels, upon fibrin gels, and upon laminin. The length of neurites within three-dimensional matrices of fibrin was decreased in a concentration-dependent manner by agents that inhibited plasmin, e.g. aprotinin, or that inhibited plasminogen activation, e.g., epsilon-aminocaproic acid (EACA), or plasminogen antiserum. In contrast, such agents increased the length of neurites growing out from DRGs cultured upon two-dimensional substrates of fibrin and had no effect on the length of neurites growing out from DRGs cultured upon laminin. Visualization of neurites within three-dimensional fibrin matrices demonstrated that the distance between fibrin strands was much smaller than the diameter of neurites. All these data were consistent with the hypothesis that fibrinolysis localized to the region of the neurite tip is an important mechanism for neurite penetration of a physical barrier of fibrin strands arranged in a three-dimensional matrix.