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Biomedical subjects

M D Lelah

Publications and source records attributed to M D Lelah.

13 recordsLinked to original sources

A modification of cellulose that facilitates the control of complement activation.

Complement activation by Cuprophan hemodialysis membranes has been linked to a variety of pathological sequelae (neutropenia and various cardiopulmonary manifestations) seen in the clinical setting. The modification of reactive surface hydroxyl groups on regenerated cellulose with various dicarboxylic-acid anhydrides has been found to significantly limit the complement-activating potential of these materials. Of the anhydrides tested, maleic anhydride appears to display the most dramatic and consistent diminution of complement activation compared to unmodified cellulose (0-10% of control values for C3b deposition and C3a/C5a production). Current evidence suggests that this maleated derivative facilitates the factor-H control of C3 and C5 convertase activity and thus may help limit complement activation by normal regulatory mechanisms. In addition, this modification may help limit the production of other inflammatory mediators that may result in diminished levels of cellular activation.

Biocompatible Materials↗

Ex vivo interactions and surface property relationships of polyetherurethanes.

Despite the use of polyurethanes in a number of blood-contacting applications, little is known about the contributing effects of the various polyurethane components in thrombogenesis. In order to investigate blood-polyurethane interactions, a number of different polyurethanes were examined in an acute canine ex vivo series shunt experiment. Multiprobe surface characterization techniques, including contact angle measurements, ESCA, ATR-IR, and SEM were used to obtain surface property information on the materials studied. The polyurethanes examined included several with different soft segment types, a series of materials with different hard segment diisocyanates and chain extenders, a series consisting of the same polymer cast from different solvents, a zwitterionomer, and a hard segment analog. Two commercial urethanes were also examined, and the effect of methanol extraction on these materials was studied. The blood-contact and surface characterization results indicated that both the surface concentration and type of hard segment were of importance in determining blood response. The relative concentration of hard segment on the polymer surface was found to affect the observed blood-material interaction, although the extent of this effect was found to depend on the hard and soft segment components of the copolymer system. Both the surface properties and thrombogenicity of a particular polyurethane were changed by casting from different solvents, indicating the need to optimize and control fabrication conditions. Methanol extraction was found to improve the thromboresistance of the commercial polyurethanes.

Animals↗

In vitro vs. ex vivo platelet deposition on polymer surfaces.

The initial adherence and activation of platelets on a surface may be a major determinant of the thrombogenicity of that surface. The response of platelets to four polymers: polyethylene (PE), polyvinyl chloride (PVC), silicone rubber (SIL), and oxidized polyethylene (OX-PE) was studied in vitro with scanning electron microscopy. Platelets from mongrel canines and rhesus monkeys were obtained just prior to cannulation of the donor animal with an ex vivo arteriovenous series shunt evaluating the same four polymers. Thus, the in vivo response of circulating platelets could be compared to the in vitro response of purified platelets from the same animal. In the canine the in vitro response of individual platelets deposited on the four polymers studied was nearly the same as the ex vivo response although the extent of shape-change was usually somewhat greater ex vivo. Large numbers of fully spread platelets were seen on OX-PE and fewer numbers on PE both in vitro and ex vivo. Mixtures of platelets in all degrees of shape-change/activation wer characteristic on PVC, while platelets on SIL showed little shape-change over all time intervals. Rhesus platelet response was similar to the canines' except that fewer attached or shape-changed, and differences in responses to the four polymers were less pronounced. The similarity of the in vitro to the ex vivo response in each of the species suggests that this simple in vitro model can be informative in studying platelet shape-change/activation as a precursor to surface induced thrombosis with less complexity and expense than in vivo methods.

Adenosine Diphosphate↗

Physicochemical characterization and in vivo blood tolerability of cast and extruded Biomer.

Solution grade and extruded grade Biomer (SB and EB, respectively) are polyurethanes that have been suggested for use in biomedical applications. The bulk materials were examined by elemental analysis, differential scanning calorimetry, thermomechanical testing, and stress-strain testing. The extruded grade material has a lower soft segment molecular weight (650 g/mol) than the solution grade material (2000 g/mol). As a result of its higher molecular weight, the soft segment phase of SB is semicrystalline in the solid state. The hard segments of the extruded grade material are chain extended with water yielding a lower urea concentration than in the solution grade material in which the hard segments are chain extended with diamines. Chemical structures for the two materials consistent with elemental analysis, urea/urethane ratios and thermal and mechanical data, are proposed. X-ray photoelectron spectroscopy (ESCA) was used to analyze the surfaces of extruded grade Biomer, solution grade Biomer cast on the inner surface of polyethylene tubing, and extruded grade Biomer dissolved in DMA and similarly cast on polyethylene (CB). Soft segment concentrations were highest on the EB surface and lowest on the SB surface. Soft segment concentrations on the EB surface were higher than on the CB surface, indicating that the method of fabrication affected the composition of the surface layer. The three materials were tested for blood tolerance in a canine femoral arteriovenous shunt configuration. Blood compatibility was correlated with increasing concentration of polyether soft segments on the surface.

Animals↗

Morphological changes occurring during thrombogenesis and embolization on biomaterials in a canine ex-vivo series shunt.

An acute canine ex-vivo femoral A-V shunt technique was used to study thrombus formation and embolization on a number of porous and non-porous polymer surfaces over a one-hour blood contact period. The technique allows for simultaneous exposure of all the surfaces under similar physiological and hematological conditions. This makes comparisons between surfaces more reliable. SEM was used to study changes in the morphology of platelets and thrombi present on the polymer surfaces. Quantitative information was obtained using radiolabeled platelets. In general, platelet deposition, activation, and aggregation was followed by thrombus formation which peaked at about 15-30 minutes of blood contact. Thrombi were composed mainly of platelets with few leukocytes present. Embolization was observed on Silastic (SIL), polyvinylchoride (PVC), polyethylene (PE), and oxidized polyethylene (OX-PE) surfaces between 20 and 60 minutes of blood contact. The mechanism for embolization involved clot retraction under the influence of a shear field. Leukocytes did not appear to be necessary for the initiation of embolization but were present during the embolization phase on OX-PE, possibly due to chemotactic factors. Although extensive thrombus formation was observed on the porous PTFE materials (GORE-TEX and IMPRA), the thrombi formed were flat and did not significantly block the lumen. By 60 minutes of blood contact, only minimal embolization had occurred on the PTFE surfaces. SEM examination of the sequence of thrombus formation and embolization was found to correlate well with trends in platelet deposition measured using radiolabeling techniques.

Animals↗

Cast vs extruded Biomer for biomedical applications.

The properties of solution grade and extrusion grade Biomer have been investigated and compared. In vivo blood compatibility studies using arteriovenous (AV) shunts of the cast and extruded materials show that extruded Biomer is more thromboresistant than solution cast Biomer. This has important implications for long-term implantation studies, since solution cast Biomer is used in artificial hearts. This study also indicates that extruded Biomer, dissolved in DMA and then solution cast, is more thromboresistant than cast solution grade Biomer. Surface studies using ESCA indicate a correlation between thromboresistance and surface soft segment concentration.

Animals↗

A canine ex vivo series shunt for evaluating thrombus deposition on polymer surfaces.

A new acute canine ex vivo femoral A-V series shunt experiment is described. Platelet and fibrinogen deposition on a series of up to ten different polymers may be tested in the same nonanticoagulated animal. The method reduces the time and expense associated with animal testing, and also allows for the simultaneous monitoring of platelet and fibrinogen deposition on a number of polymer surfaces. The series shunt technique was used to examine platelet and fibrinogen deposition on polyethylene, Silastic, polyvinylchloride, and oxidized polyethylene surfaces. Following an initial period of minimal deposition, platelet deposition increased dramatically to a peak by about 15-20 min of blood contact on all surfaces studied. The amount of adsorbed fibrinogen fell from initial levels to a minimum at about 5-10 min of blood contact and then increased to a peak at about the same time as observed for the platelet response. Oxidized polyethylene was the most thrombogenic surface studied, followed by polyethylene, polyvinylchloride, and Silastic. Peak platelet and fibrinogen levels were found to be inversely related to flow rate over the range studied. In this experiment it appears that the interaction of blood components with a foreign surface in vivo or ex vivo is localized to the interface with the flowing blood. Within experimental errors, no effect of segment position or any downstream effects were observed. These results suggest that a series shunt may be used to investigate the short-term interactions of blood with a number of test surfaces.

Adenosine Diphosphate↗

The measurement of contact angles on circular tubing surfaces using the captive bubble technique.

Circular tubings are used extensively in biomedical implants and devices. It is desirable to determine contact angles on the inner or outer surfaces of such tubing in its final fabricated form. In this study, a technique for the measurement of contact angles on tubing surfaces in an aqueous environment is reported. This has particular applications to biomaterials research, where polymer tubings contact the biologic environment. In this technique, air or octane captive bubble dimensions can be measured, and an underwater contact angle calculated from these dimensions. The validity of the technique was experimentally confirmed using Solution Grade Biomer and NIH standard polyethylene surfaces.

Air↗

External catheter immobilization improves wound healing in micropigs.

Recurrent traumatic damage by mechanical action is a major cause of catheter exit site problems in CAPD patients. The purpose of this study was to determine the efficacy of a new external immobilization device (Immobilizer) on wound healing characteristics at the catheter exit site. Sixteen Tenckhoff catheters were surgically implanted in four Yucatan micropigs (two catheters per flank). Immobilization devices were placed on one catheter on each side of each animal; the other catheter was allowed free movement. The devices were changed daily, and exit sites were examined for wound healing progress and infection. Fourteen days following implantation the animals were sacrificed, and the catheter exit sites explanted for histologic examination. The results of this study suggest that immobilization of catheters with this device improves wound healing at the exit site, as evidenced by decreased (p less than 0.05) marsupialization/epidermal down-growth (nonimmobilized 2.9 mm vs. immobilized 1.6 mm), and an increased (p less than 0.05) macrophage/epithelioid cell/giant cell response within the exit tract or in the Dacron cuff (granulomatous response histology score of 2.3 for immobilized vs. a histology score of 1.6 for nonimmobilized). Thus, use of this device may help reduce catheter exit site problems in CAPD patients.

Animals↗