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Biomedical subjects

K P Andriano

Publications and source records attributed to K P Andriano.

17 recordsLinked to original sources
PubMed2000

Preliminary in vivo studies on the osteogenic potential of bone morphogenetic proteins delivered from an absorbable puttylike polymer matrix.

This article describes preliminary in vivo studies evaluating the osteogeneic potential of bone morphogenetic proteins (BMPs) delivered from an absorbable puttylike polymer matrix. In the first study, bovine-derived bone morphogenetic proteins were incorporated in an polymer matrix consisting of 50:50 poly(DL-lactide-co-glycolide) dissolved in N-methyl-2-pyrrolidone. The matrix was implanted in an 8 mm critical-size calvarial defect created in the skull of adult Sprague-Dawley rats (n = 5 per treatment group). After 28 days, the implant sites were removed and examined for new bone formation, polymer degradation, and tissue reaction. Gamma-irradiated polymer matrices appeared to give more bone formation than nonirradiated samples (histological analysis; 2. 76 + 1.34 mm(2) of bone versus 1.30 + 0.90 mm(2) of bone, respectively and x-ray analysis; 27.2 + 15.9 mm(2) of bone versus 20. 7 + 16.7 mm(2) of bone, respectively) and less residual polymer (0.0 + 0.0 versus 0.2 + 0.4, respectively). The polymer implants with bone morphogenetic protein also gave less inflammatory response than the polymer controls (gamma irradiated polymer/BMP = 1.8 + 0.4 and nonirradiated polymer/BMP = 1.2 + 0.4 versus polymer only = 3.0 + 1. 2, respectively). However, despite trends in both the x-ray and histological data there was no statistical difference in the amount of new bone formed among the four treatment groups (P > 0.05). This was most likely due to the large variance in the data scatter and the small number of animals per group. In the second animal study, bovine-derived BMPs and the polymeric carrier were gamma irradiated separately, at doses of 1.5 or 2.5 Mrad, and their ability to form bone in a rat skull onlay model was evaluated using Sprague-Dawley rats (n = 5 per treatment group). Histomorphometry of skull caps harvested 28 days after implantation showed no significant differences as compared to non-irradiated samples, in implant area, new bone area, and percent new bone (P > 0.05). These results suggest gamma irradiation may be useful in sterilization of the bovine-derived BMPs and the polymeric carrier for potential bone repair and/or regeneration applications.

Animals↗
PubMed1999

Technical note: biomechanical analysis of two absorbable fracture fixation pins after long-term canine implantation.

The design requirements for bioabsorbable fracture fixation devices for specific applications are as yet unknown. Therefore, a range of initial mechanical properties and degradation kinetics may provide developers with additional choices for the design of absorbable fracture fixation devices. This study evaluated the changes in push-out strength, polymer mechanical properties, and bone mechanical properties of self-reinforced poly(glycolide) (SR-PGA) and poly(ortho ester) (POE) fracture fixation pins implanted into the canine femoral canal for 18 months. Mechanical testing indicated that SR-PGA pins had degraded to a pasty consistency by 3 months, showing complete loss of all mechanical properties. Meanwhile, POE pins showed a simultaneous linear decrease in both compressive strength and stiffness to almost zero by the end of the study period, suggesting that these devices were undergoing surface erosion. However, changes in specimen diameter, which would support this mechanism, were not apparent. The decrease in polymer density after 12 months suggests that there was an increase in bulk erosion for POE devices. This was further supported by the observation of internal polymer resorption noticed in specimen cross-sections after 18 months. This observation appears to be related to the method of polymer processing; hot-compression molding of fine powdered polymer. The appearance of grain boundaries would provide a path for water to penetrate into the bulk polymer and cause autocatalysis in the interior of the implant.

Absorption↗
PubMed1999

In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering.

This article describes preliminary in vitro and in vivo studies comparing bulk and surface hydrolysis in absorbable polymer scaffolds proposed for tissue engineering of bone. The two polymers systems used were a bulk hydrolyzing 50:50 poly(DL-lactide-co-glycolide) (PLGA) and a surface hydrolyzing self-catalytic poly(ortho ester) (POE). Polymer scaffolds were exposed to physiological saline at body temperature and changes in polymer mass loss and inherent viscosity were monitored over time. New bone formation and local tissue response were evaluated by implanting scaffold disks of both polymer systems into non-critical-size calvarial defects in rabbits. New bone formation was determined by bone mineral density measurements, and local tissue response was determined by qualitative histology. Preliminary results confirmed that one of the main design characteristics for absorbable polymers in tissue engineering of bone, coordination of controlled polymer mass loss with new tissue formation, appeared to be achieved better using a surface hydrolyzing POE, rather than with a bulk hydrolyzing 50:50 PLGA. Bone mineral density at 6 and 12 weeks was an average 25% higher in the surface hydrolyzing scaffold. Unfortunately, the amount of bone formed was so inconsequential that this observation is of little relevance. Use of a water-soluble signaling factor such as basic fibroblast growth factor (bFGF) failed to increase bone formation. The histological response of these two polymer systems was similar and unaffected by the presence or absence of bFGF. The persistence of structural integrity for self-catalytic POE scaffolds after 6 and 12 weeks implantation, while 50:50 PLGA scaffolds had partially collapsed after 6 weeks, suggests surface hydrolyzing scaffolds may have some advantage over bulk hydrolyzing scaffolds in resisting normal in vivo stresses when used in a calvarial defect.

Animals↗
PubMed1995

Preliminary effects of in vitro lipid exposure on absorbable poly(ortho ester) films.

Bioabsorbable films show promise in preventing postoperative interfacial tissue adhesion. Absorbable polymers in film form are generally more sensitive to chemical environments, due to their large surface area to volume ratio. The in vivo environment contains lipids such as cholesterol, triglycerides, and phospholipids, which are known to affect the degradation of permanent and absorbable polymeric biomaterials. Preliminary investigations of in vitro lipid exposure of bioabsorbable poly(ortho ester) (POE) films for implant use are described. POE has been studied previously for use in controlled drug delivery and fracture fixation. Six-week in vitro exposure of 65:35 POE films to a cholesterol emulsion (1 g/L) showed no apparent difference in hydrolytic degradation rates of mechanical properties or mass loss compared to deionized water exposed films. Decreases of 28 and 6% in inherent viscosity were observed after 5 weeks for cholesterol and deionized water exposed films, respectively, suggesting cholesterol may have some effect. Further examination of the data, due to sample variation, revealed that clear, uniform films showed only minor changes in mass loss and mechanical properties after 6 weeks in either of the in vitro media. But slightly cloudy films possessing microscopic bubbles showed accelerated degradation in both media, indicating the effect of cholesterol was inconclusive due to sample variation. Control of the microbubble formation process could have utility in controlling hydrolytic degradation of POE films.

Biocompatible Materials↗
PubMed1994

Evaluation of absorbable poly(ortho esters) for use in surgical implants.

Recent reports describe an unfavorable noninfective inflammatory response to acidic degradation products in clinical applications of bone fixation devices fabricated from bulk hydrolyzing polyglycolides and polylactides (PGA and PLA). The work described here suggests that poly(ortho esters) (POEs) offer an alternative. By comparison, hydrophobic POEs degrade predominately via surface hydrolysis, yielding first a combination of nonacidic degradation products, followed by alcoholic and acidic products gradually over time. POE specimens proved acutely nontoxic in United States Pharmacopeia tests of cellular, intracutaneous, systemic, and intramuscular implant toxicity. Hot-molded specimens degraded slowly in saline, retaining 92% initial stiffness (1.6 GPa flexion) and retaining 80% initial strength (66 MPa flexion) in 12 weeks. Degradation was almost unaffected by decreasing saline pH from 7.4 to 5.0. This demonstrated the relative hydrophobicity of POEs, since incorporation of small amounts of acid within the polymer markedly increases the degradation rate. Degradation rates were increased substantially by dynamic mechanical loading in saline. This may be true for other degradable polymers also, but no data could be found in the literature. Presumably, tensile loading opens microcracks, allowing water to enter. Solvent cast POE films were strong in tension (30 + MPa tensile yield) and reasonably tough (12-15% elongation to yield). Higher molecular weight films (41-67 kDa) showed no degradation in mechanical properties after 31 days in physiological buffer at body temperature. A 27-kDa film offered similar initial strength and stiffness but began showing mechanical degradation at 31 days. The films showed a decrease in weight with exposure time but no change in either molecular weight or water absorption at 31 days, further supporting the observation that POE degrades by surface hydrolysis rather than by bulk hydrolysis.

Animals↗
PubMed1994

Processing and characterization of absorbable polylactide polymers for use in surgical implants.

Absorbable fibers of linear poly-alpha-hydroxy acids have been used successfully in providing temporary scaffolds for tissue regeneration. In some surgical applications, degradation rates for poly(glycolide) (PGA) are too high, but implants of poly(L-lactide) (PLLA) fibers may degrade too slowly for optimal function. Polymers produced by copolymerization of L-lactide with varying amounts of D-lactide may offer an alternative choice for absorbable fiber based implants. Poly(L/D-lactide) stereocopolymers with L/D lactide molar ratios of 95/5, 90/10, and 85/15 were considered. Melt-spun/hot-drawn fibers with L/D molar ratios of 90/10 and 85/15 and draw ratios ranging from 3.0 to 8.9 were further evaluated by mechanical testing, differential scanning calorimetry, birefringence, x-ray diffraction, and in vitro exposure to pH 7.4 phosphate buffered saline at 37 degrees C. Fabrication was reproducible and results indicated that tensile strength, modulus, an birefringence all increased with increasing draw ratio up to a draw ratio of 6.7 and declined thereafter; elongation to failure decreased for the entire range studied. For fibers with a draw ratio of 6.7, there was a 10% relative difference in crystallinity between the 90/10 and 85/15 lactide fibers (90/10 was higher). Wet strength retention after 12 weeks in vitro exposure was approximately 10% for the 90/10 fibers and 30% for the 85/15 fibers. The intermediate wet strength retention of lactide stereocopolymer fibers when compared to reported values for PGA and PLLA fibers, suggests these materials may be useful in absorbable surgical implants for tissue repair and regeneration.

Biocompatible Materials↗
PubMed1994

Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗
PubMed1993

Preliminary biocompatibility screening of several biodegradable phosphate fiber reinforced polymers.

This article describes preliminary biocompatibility screening of three degradable phosphate fibers containing K +, Ca +2/Na + and Na +/Ca +2/Al +3 ions in the polymer chain, and of several different degradable polymers reinforced with these fibers. Biodegradable phosphate fibers of calcium-sodium-metaphosphate (CSM) and sodium-calcium-aluminum-polyphosphate (NCAP) were acutely nontoxic in cellular, tissue, and whole animal evaluations, as determined by standard acute toxicity tests. Histological studies of bone implants sites fabricated from composites of copolymers of poly(E-caprolactone/L-lactide) and poly(ortho ester) reinforced with either CSM or NCAP fibers showed these composite materials to be nontoxic, with no abnormal inflammatory response. However, histological evaluation of muscle implants sites revealed the appearance of necrotic foci associated with implant sites in 12 of 22 NCAP containing composite specimens (p less than 0.05). Results of this preliminary biocompatibility screening suggest CSM fibers may be useful in reinforcing degradable polymers for production of completely biodegradable composites for implant use.

Animals↗
PubMed1992

Effectiveness of silane treatment on absorbable microfibers.

Preliminary experiments suggest pretreatment of absorbable crystalline, calcium-sodium-metaphosphate (CSM) microfibers with trimethoxy-based silane coupling agents yields a polysiloxane film barrier which protects the fiber surface from early dissolution due to water. Compared to thermoplastic poly(L-lactic acid) (PLLA) composites reinforced with untreated fibers, PLLA composites reinforced with a variety of silane pretreated microfibers showed increased mechanical properties, suggesting improved adhesion was achieved at the fiber/matrix interface. Unfortunately, the silane pretreated CSM/PLLA composite showed no increase in wet strength retention after short-term in vitro exposure. This may be due to plasticization from water entering the composite at areas of incomplete fiber wetting by the highly viscous molten PLLA. However, when a nonabsorbable, low viscosity unsaturated polyester thermoset resin was reinforced with methacryloxy-silane pretreated CSM microfibers, there was no decrease in flexural strength and less than a 10% decrease in flexural modulus after 7 days exposure to 7.4 pH Tris-buffered saline at 37 degrees C.

Biodegradation, Environmental↗
PubMed1992

Biocompatibility and mechanical properties of a totally absorbable composite material for orthopaedic fixation devices.

Bioabsorbable polymer/inorganic phosphate fiber composites are prone to rapid degradation due to water sensitivity of the interface between the degradable polymer and the degradable fiber. This article describes successful fabrication and laboratory evaluation of a candidate bioabsorbable composite implant material with mechanical properties similar to bone. The composite studied was poly(ortho ester) reinforced with randomly-oriented, crystalline microfibers of calcium-sodium-metaphosphate. The component materials showed no acute cytotoxicity as determined by tissue culture agar overlay. Treating the microfibers with a diamine-silane coupling agent improved mechanical properties and slowed degradation in saline, but strength still decreased 50% in 1 week. When the composite material was then coated with a layer of matrix polymer alone it retained 70% of its strength and 70% of its stiffness after 4 weeks exposure to 7.4 pH Tris-buffered saline at body temperature. The marked improvement with the coating can be attributed to the hydrophobicity of poly(ortho esters).

Biodegradation, Environmental↗
PubMed1990

Mechanical properties of biodegradable polymers and composites proposed for internal fixation of bone.

The mechanical properties of biodegradable polymers and composites proposed for use in internal fixation (in place of stainless steel) are crucial to the performance of devices made from them for support of healing bone. To assess the reported range of properties and degradation rates, we searched and reviewed papers and abstracts published in English from 1980 through 1988. Mechanical property data were found for poly(lactic acid), poly(glycolic acid), poly(epsilon-caprolactone), polydioxanone, poly(ortho ester), poly(ethylene oxide), and/or their copolymers. Reports of composites based on several of these materials, reinforced with nondegradable and degradable fibers, were also found. The largest group of studies involved poly(lactic acid). Mechanical test methods varied widely, and studies of the degradation of mechanical properties were performed under a variety of conditions, mostly in vitro rather than in vivo. Compared to annealed stainless steel, unreinforced biodegradable polymers were initially up to 36% as strong in tension and 54% in bending, but only about 3% as stiff in either test mode. With fiber reinforcement, reported highest initial strengths exceeded that of stainless steel. Stiffness reached 62% of stainless steel with nondegradable carbon fibers, 15% with degradable inorganic fibers, but only 5% with degradable polymeric fibers. The slowest-degrading unreinforced biodegradable polymers were poly(L-lactic acid) and poly(ortho ester). Biodegradable composites with carbon or inorganic fibers generally lost strength rapidly, with a slower loss of stiffness, suggesting the difficulty of fiber-matrix coupling in these systems. The strength of composites reinforced with (lower modulus) degradable polymeric fibers decreased more slowly. Low implant stiffness might be expected to allow too much bone motion for satisfactory healing. However, unreinforced or degradable polymeric fiber reinforced materials have been used successfully clinically. The key has been careful selection of applications, plus use of designs and fixation methods distinctly different from those appropriate for stainless steel devices.

Biocompatible Materials↗
PubMed1987

Automated measurement of functional residual capacity by sulfur hexafluoride washout.

We have constructed a computerized, totally automated system for measuring functional residual capacity (FRC) during mechanical ventilation, at any positive end-expiratory pressure (PEEP) and fraction of inspired oxygen. This system uses washout of a small amount (0.5 to 1.0%) of an insoluble, nontoxic tracer gas, sulfur hexafluoride, to measure FRC. It requires no modification of the ventilator and only minimal changes in the breathing circuit; it can be programmed to make measurements routinely without manual intervention. The system was evaluated with three tests. The prototype sulfur hexafluoride analyzer characteristic curve was determined, and the analyzer was evaluated to determine carbon dioxide interference. A comparison with nitrogen washout FRC measurements was made in an extensive bench test with a Plexiglas lung model. The bench test was designed to determine the effects of changing gas composition and minute volume. A study was done in six healthy dogs to determine reproducibility of the FRC measurements at four PEEP levels (0, 5, 10, and 15 cm H2O: two repetitions in each animal). The sulfur hexafluoride analyzer was well characterized by an exponential equation with a multiple r2 = 0.996. The analyzer was not affected by the presence of carbon dioxide (paired t test, t19 = 1.23, P greater than 0.10). The bench test indicated that FRC (measured) = 0.969 X FRC (true) - 5.3 ml. (Multiple r2 = 0.979.) This was significantly better than the nitrogen washout system, whose regression equation was also a function of minute volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Variability of the respiratory response to diazepam.

The authors investigated the respiratory effects of diazepam in 24 healthy volunteers using a modified Read rebreathing circuit. Resting end-tidal CO2 (PETCO2) and the slopes of the ventilatory (VE/PETCO2) and occlusion pressure (P0.1/PETCO2) response to CO2 were measured just prior to and 5, 20, 40, and 60 min after diazepam, 0.1 mg/kg iv. The slope of VE/PETCO2 for all 24 subjects analyzed as a single group was never significantly depressed. The slope of P0.1/PETCO2 for all 24 subjects analyzed as a single group was significantly depressed only at 5 min after diazepam. The resting PETCO2, however, had small but statistically significant increases throughout the 1 h of study. Group or cluster analysis of the slope of P0.1/PETCO2 clearly divided subjects into one group of five subjects, whose P0.1/PETCO2 slope was significantly and consistently augmented for 1 h and a second group of 19 subjects whose P0.1/PETCO2 slope was always less than control for the entire hour. Diazepam may, through effects on pulmonary mechanics and/or the central nervous system, sometimes enhance respiratory responses to CO2 rebreathing. Failure to select for such group effects when studying drug effects by CO2 rebreathing may obscure the severity and duration of respiratory depression that occurs in the majority of individuals. Resting PETCO2 indicated consistent depression of resting minute ventilation by diazepam and may be a more appropriate or sensitive measure of mild or subtle drug-induced respiratory effects.

Adult↗
PubMed1986

Computer-controlled optimization of positive end-expiratory pressure.

Positive end-expiratory pressure (PEEP) is a standard treatment for patients with refractory hypoxemia due to an acute restrictive pathology. The therapeutic range of PEEP can be quite narrow. PEEP therapy has been optimized using invasive variables such as oxygen transport and pulmonary shunt, and noninvasive variables such as compliance; however, the measurements are complex. We constructed a computerized PEEP-optimization system consisting of a Siemens 900C ventilator, Siemens prototype sulfur hexafluoride analyzer, Siemens 940 lung mechanics analyzer, and a DEC 11/23 microcomputer. The user may choose from three different noninvasive PEEP titration algorithms: maximizing static total respiratory system compliance (CTR), maximizing functional residual capacity(FRC)-based compliance (CFRC), and normalizing FRC. The device was tested in six dogs with pulmonary injury induced by oleic acid. The system was constrained to 3-cm H2O PEEP steps at 20-min intervals. The algorithm normalizing FRC reached optimal PEEP levels in 40 min, with a mean difference from the desired FRC of 15 +/- 48 (SEM) ml. This corresponds to a mean percent error of 1.0% +/- 2.63%. The CFRC and CTR algorithms reached optimal PEEP levels in 60 and 40 min, respectively, and maintained a maximal compliance for 85% of the time. This system provides fully automated noninvasive PEEP titration and is flexible enough to incorporate easily any other PEEP titration algorithms. It should improve patient care by guaranteeing that PEEP therapy is truly optimized throughout the patient's recovery.

Animals↗
PubMed1985

Transcutaneous PO2 poorly estimates arterial PO2 in adults during anesthesia.

We compared values of PaO2 and transcutaneous PO2 in 21 adult patients during anesthesia. In 282 simultaneous determinations during anesthetic periods of 3-10 h, transcutaneous PO2 was a poor predictor of absolute PaO2 and changes in PaO2. Transcutaneous PO2 monitoring in adults during anesthesia is of unproven value.

Adult↗
PubMed1982

Epinephrine-induced arrhythmias during halothane anesthesia with the addition of nitrous oxide, nitrogen, or helium in dogs.

The arrhythmogenicity of epinephrine was examined in 34 male mongrel dogs awake and during 1.1 MAC steady state halothane-O2 anesthesia with the addition of 50% N2O, nitrogen, or helium. All anesthetized dogs required more epinephrine than did awake dogs to produce ventricular extrasystoles. Dogs given halothane-N2O were more sensitive to the epinephrine infusion than those given halothane-nitrogen or halothane-helium. The dogs given halothane-N2O also showed a small, but statistically significant difference from dogs given halothane-O2. These results suggest that the addition of N2O to halothane increases the cardiac arrhythmic potential of epinephrine in the dog.

Animals↗