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Biomedical subjects

J A Hubbell

Publications and source records attributed to J A Hubbell.

At least 73 records · Page 4Linked to original sources
PubMed1996

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.

Abdomen↗
PubMed1996

Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels.

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.

Animals↗
PubMed1996

Alkylation of cellulosic membranes results in reduced complement activation.

4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both C10 and C16 aliphatic chains. Complement activation of heparinized human blood, corrected for anaphylatoxin adhesion, was measured by radioimmunoassay. The surface treatments both yielded substantial reductions in C5a activity, with a lessor reduction in C3a and C4a activity. Alkylation with 10 and 16 carbon chains resulted both in enhancements of albumin adsorption and stability. These enhancements as well as the reductions in complement activation were statistically indistinguishable between the two treatments. The reduction in complement activation was influenced more by adsorption of endogenous albumin and possibly by the vinyl pyridine graft, than the removal of surface active hydroxyl groups from Cuprophan.

Adsorption↗
PubMed1996

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. III. Ventilation, respiratory monitoring, treatment for postoperative pain].

The purpose of this study was to review ventilation and postoperative analgesic technics in 137 dogs and 13 cats with congenital or acquired heart disease. The animals were referred to the Department of Veterinary Clinical Sciences at The Ohio State University, U.S.A, for the following surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch ring anomaly (3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). Controlled ventilation was used in all animals during thoracotomy. Anesthesia was maintained over 2.3 +/- 1.3 hours by using either isoflurane, halothane, propofol, or diazepam-ketamine in 64%, 32%, 2%, and 0.7% of animals, respectively. Postoperative analgesia was necessary in 20% of animals and was provided by using different technics over several hours. The technics and respective percentages of animals in which they were used, were: intravenous buprenorphine (3.3%), intercostal nerve blocks (8.7%), epidural morphine (4%), and interpleural regional analgesia (4%).

Analgesia↗
PubMed1996

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.

Animals↗
PubMed1995

Densely crosslinked polymer networks of poly(ethylene glycol) in trimethylolpropane triacrylate for cell-adhesion-resistant surfaces.

Densely crosslinked semi-interpenetrating polymer networks (semi-IPNs) of poly(ethylene glycol) (PEG) were synthesized by photopolymerizing a melt of PEG of various molecular weights and end-group functionalities in neat trimethylolpropane triacrylate (TMPTA). Increasing the molecular weight of PEG in the matrix from 1000 to 100,000 g/mol reduced the advancing and receding contact angles, contact angle hysteresis, and adsorption of human fibrinogen and bovine serum albumin. Crosslinked TMPTA homonetworks supported human fibroblast adhesion in vitro, whereas the resistance to cell adhesion of the semi-IPNs depended upon PEG molecular weight: Lower molecular weight PEG reduced the number of adherent cells; higher molecular weight PEG further reduced and eliminated cell adhesion, as did networks containing acrylate-functionalized PEG. A polymer system incorporated with PEG throughout a hydrophobic, densely crosslinked matrix, rather than as a blend or surface treatment, may be particularly useful for limiting biologic interactions when bulk material properties must be independent of the solvent environment and where surface abrasion may occur.

Acrylates↗
PubMed1995

Local release of fibrinolytic agents for adhesion prevention.

Tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), and streptokinase were evaluated for their ability to reduce postsurgical adhesion formation in a rat uterine horn devascularization and serosal injury model in a blinded, randomized study. Small doses of tPA, uPA, or streptokinase were delivered over approximately a 4-day period either from a biodegradable hydrogel matrix or as four daily intraperitoneal injections. The hydrogel was formed upon the uterine horns by photopolymerization of an aqueous precursor solution containing dissolved drug. A control group that received no treatment had an average extent of adhesion formation of 72 +/- 15% (mean +/- SEM, percentage of the length of the uterine horns involved in adhesions). Application of this formulation of the hydrogel alone reduced the extent of adhesion formation to 22 +/- 10% by functioning as a mechanical barrier. When tPA was released from the hydrogel, adhesion formation was reduced to 4 +/- 3%, while when tPA was given by intraperitoneal injection, adhesion formation was only reduced to 49 +/- 8%. Local delivery of urokinase reduced adhesion formation to 6 +/- 6%, but intraperitoneal injection of urokinase did not reduce adhesion formation. Streptokinase did not reduce adhesion formation when administered by intraperitoneal injection and increased adhesion formation to 45 +/- 9% when locally released relative to the hydrogel alone. These results suggest that both tPA and uPA may be used to prevent adhesion formation when delivered locally.

Animals↗
PubMed1995

Comparison of covalently and physically cross-linked polyethylene glycol-based hydrogels for the prevention of postoperative adhesions in a rat model.

A covalently and a physicochemically cross-linked hydrogel, both based primarily on polyethylene glycol and both formed in situ, were compared side by side in a rat uterine horn devascularization and serosal injury model for efficacy in adhesion prevention. The primary difference between the two materials was the nature of their cross-linking. The covalently cross-linked hydrogel was a photopolymerized polyethylene glycol-co-lactic acid diacrylate, and the physically cross-linked hydrogel was a polyethylene glycol-co-polypropylene glycol, Poloxamer 407. In the surgical model employed, application of the covalently cross-linked hydrogel reduced the extent of adhesion formation from 75 +/- 10% in the control group to 16 +/- 6% (mean +/- s.d., P < 0.001). Application of the physically cross-linked hydrogel reduced adhesion formation to 38 +/- 19% (P < 0.01). Retention of the two hydrogels upon the site of application was also evaluated. The covalently cross-linked hydrogel formed a continuous barrier upon the uterine horns for more than 4 d, while the physicochemically cross-linked hydrogel was present upon the uterine horns for less than 2 d. This difference in retention was probably the cause of the difference in efficacy and may be attributed to the nature of the cross-linking.

Animals↗
PubMed1995

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.

Acrylates↗
PubMed1995

Biomaterials in tissue engineering.

Biomaterials play a pivotal role in field of tissue engineering. Biomimetic synthetic polymers have been created to elicit specific cellular functions and to direct cell-cell interactions both in implants that are initially cell-free, which may serve as matrices to conduct tissue regeneration, and in implants to support cell transplantation. Biomimetic approaches have been based on polymers endowed with bioadhesive receptor-binding peptides and mono- and oligosaccharides. These materials have been patterned in two- and three-dimensions to generate model multicellular tissue architectures, and this approach may be useful in future efforts to generate complex organizations of multiple cell types. Natural polymers have also played an important role in these efforts, and recombinant polymers that combine the beneficial aspects of natural polymers with many of the desirable features of synthetic polymers have been designed and produced. Biomaterials have been employed to conduct and accelerate otherwise naturally occurring phenomena, such as tissue regeneration in wound healing in the otherwise healthy subject; to induce cellular responses that might not be normally present, such as healing in a diseased subject or the generation of a new vascular bed to receive a subsequent cell transplant; and to block natural phenomena, such as the immune rejection of cell transplants from other species or the transmission of growth factor signals that stimulate scar formation. This review introduces the biomaterials and describes their application in the engineering of new tissues and the manipulation of tissue responses.

Amino Acid Sequence↗
PubMed1995

Kinetics of glucose delivery to subcutaneous tissue in rats measured with 0.3-mm amperometric microsensors.

The time between intravenous injection of a glucose bolus and the time the glucose concentration peaked in the subcutaneous tissue was measured in pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric sensors. Boluses of 100, 200, and 400 mg/kg body wt were injected. The glucose concentration in the jugular vein was monitored by frequent withdrawal and analysis of samples. The glucose concentration in the subcutaneous tissue was continuously monitored with the sensors. The times required for the subcutaneously implanted sensor to reach its maximum current, corrected for sensor response times, were 7.5 +/- 3.9, 9.8 +/- 5.5, and 10.0 +/- 4.4 min for the smallest to the largest dose, respectively. The shorter delay in response to the smallest dose was statistically significant (P < 0.03). The results were consistent with dilution of the bolus in the cardiovascular system and transport of glucose by both diffusion and facilitated transport via a saturable mediator. An understanding of the differences in the dynamics of venous vs. subcutaneous response to a glucose dose is important in developing algorithms for the control of blood glucose based on a subcutaneous measurement.

Animals↗
PubMed1995

Alkylated cellulosic membranes with enhanced albumin affinity: influence of competing proteins.

4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both non-fatty acid-like C10 (GVP-C10) and fatty acid-like C16 (GVP-C16) aliphatic chains. In vitro albumin adsorption studies from single and binary protein solutions, as well as from dilute plasma demonstrated a significant enhancement (1.4-3.89 times) of albumin binding to both the GVP-C10 and GVP-C16 surfaces, relative to unmodified Cuprophan. It is speculated that enhanced albumin adsorption to a surface may improve surface thromboresistance. Further, these results suggest that there is no difference between the enhanced albumin adsorption of the fatty acid and nonfatty like alkyl chains, C10 and C16.

Adsorption↗
PubMed1995

[Sedation and anesthesia in dogs and cats with cardiovascular diseases. I. Anesthesia plan considering risk assessment, hemodynamic effects of drugs and monitoring].

The purpose of this study was to review the effects of sedatives and anesthetics in 137 dogs and 13 cats with congenital or acquired heart disease which were referred for diagnostic, therapeutic, and surgical interventions: correction of patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart-base tumors (2%), palliative surgery for ventricular septal defect (VSD, 0.7%), and sick patients with deleterious cardiac arrhythmias (0.7%). The anesthetic plan considered the risks of anesthesia based upon preoperative patient assessment, classification scheme for functional phases of heart failure, and anesthetic drug effects of the cardiovascular system. The effects of sedatives and anesthetic drugs on determinants of cardiac output are described. The most commonly used drugs for premedication, induction, and maintenance of anesthesia were midazolam-oxymorphone (20%), thiopental or etomidate (30%), and isoflurane (64%). Prompt therapy was given to control arrhythmias and provide organ perfusion, pain relief, muscle relaxation and renal diuresis, using lidocaine, dopamine, fentanyl, atracurium, and furosemide in 17.3% 14.7%, 12%, 10%, and 8.7% of animals, respectively. Methods of routine and advanced patient monitoring are described.

Anesthesia↗
PubMed1995

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)

Anastomosis, Surgical↗
PubMed1995

[Sedation and anesthesia in dogs and cats with cardiovascular disease. II. Anesthesia planning with respect to pathophysiology, heart arrhythmia].

The purpose of this study was to review the incidence of cardiac arrhythmias in 137 anesthetized dogs and 13 anesthetized cats with congenital or acquired heart disease that were referred for correction of following procedures: patent ductus arteriosus (PDA-ligation, 28%), cardiac catheterization with angiogram and angioplasty (22%), pacemaker implantation (18%), exploratory lateral thoracotomy (8.7%), correction of right aortic arch (ring anomaly, 3.3%), correction of subvalvular aortic stenosis (2.7%), correction of PDA with coil in patients with mitral regurgitation and congestive heart failure (2%), pericardectomy and removal of heart base tumor (2%), and palliative surgery for ventricular septal defect (VSD, 0.7%). The anesthetic plan considered the risks of anesthesia based upon the pathophysiology of cardiac lesions and the anesthetic drug effects on the cardiovascular system. Recommendations are made for dogs with decreased cardiac contractility, cardiac disease with volume overload, cardiac disease with pressure overload, and pericardial tamponade. The percentages of animals and their associated cardiac arrhythmias after premedication and during and after anesthesia were: sinus bradycardia (15.3%), sinus tachycardia (3.3%), atrial flutter (0.7%), atrial fibrillation (0.7%), premature ventricular contraction (14%), and ventricular tachycardia (1.3%). Prompt therapy was given to a percentage of animals in order to control arrhythmia and support cardiovascular system, by using atropine or glycopyrrolate (14%), lidocaine (17.3%), and dopamine (14.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1994

Polymer networks with grafted cell adhesion peptides for highly biospecific cell adhesive substrates.

Polymer networks of poly(ethylene glycol) (PEG) in densely cross-linked matrices of acrylic acid (AA) and trimethylolpropane triacrylate were synthesized as biospecific cell adhesive substrates. Networks grafted with synthetic adhesion peptides produced substrates to investigate long-term, receptor-mediated cell/surface interactions, without nonspecific protein adsorption producing spurious adhesion signals. PEG rendered the networks very resistant to cell adhesion in vitro, and AA provided reactive carboxyl moieties for N-terminal grafting of peptides. Networks with higher mass fractions of AA had greater background cell adhesion, which diminished with higher mass fractions of PEG such that complete resistance to cell adhesion could be obtained. Networks grafted with inactive control peptides (GRGES or no peptide) remained completely cell nonadhesive in the presence of serum or even when preincubated with adhesion proteins, while networks grafted with bioadhesive peptides (GRGDS, GYIGSRY, or GREDVY) supported morphologically complete fibroblast adhesion. The amount of AA in the network readily controlled the amount of incorporated peptide. These networks may be suitable as analytical tools specifically to investigate long-term cell/substrate interactions in the presence of serum, yet without non-specific protein adsorption producing adhesion signals other than those immobilized for study.

Acrylates↗
PubMed1994

Design, characterization, and one-point in vivo calibration of a subcutaneously implanted glucose electrode.

A 0.29-mm-diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode was designed to allow "one-point" in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. A valid zero point, along with a measurement of the glucose concentration in a withdrawn sample of blood at which the current is known, defined the sensitivity in the linear response range. The electrode was four-layered, with the layers serially deposited within a 0.125-mm recess upon the tip of a polyimide-insulated 0.25-mm gold wire. The recessed structure reduced the sensitivity to movement and allowed, through control of the depth of the recess, control of the transport of glucose and thus the range of linearity. The recess contained the four polymeric layers, with a total mass less than 5 micrograms and no leachable components. The bottom glucose concentration-to-current transducing layer consisted of the enzyme "wiring" redox polymer poly[(vinylimidazole)Os(bipyridine)2Cl]+ , complexed with recombinant glucose oxidase and cross-linked with poly(ethylene glycol) diglycidyl ether, to form an electron-conducting hydrogel. The layer was overcoated with an electrically insulating layer of polyaziridine-cross-linked poly(allylamine), on which an immobilized interference-eliminating horseradish peroxidase based film was deposited. An outer biocompatible layer was formed by photo-cross-linking derivatized poly(ethylene oxide). The current output of a typical electrode at 10 mM glucose and at 37 degrees C was 35 nA, the apparent Km was 20 mM, and the 10-90% response time was approximately 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗