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PubMed2004

Biodegradable self-expanding poly-L/D-lactic acid vascular stent: a pilot study in canine and porcine iliac arteries.

PURPOSE: To report results of an in vivo pilot study to evaluate the biocompatibility and delivery system of a new biodegradable vascular stent and validate the study design. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) and a medical stainless steel stent (Wallstent) were implanted in the common iliac arteries of 2 postpuberal female pigs and 3 laboratory-bred beagle dogs. Specimens were harvested after 45 days in the dogs and 32 days in the pigs for histomorphometry of the stented iliac artery segments. Preliminary measurements were made to assess the reliability of the quantitative histomorphometric measurements before final measurements. RESULTS: Histomorphometry analyses showed that mean luminal diameter and area were decreased in the PLA stent group (1.97+/-0.48 mm and 14+/-6.4 mm2, respectively) compared to the control stent group (4.28+/-0.83 mm and 61+/-19 mm2, respectively). The intimal thickness was higher in the PLA stent group (0.65+/-0.07 mm) than in the control group (0.44+/-0.21 mm). The mean injury score was 0.19+/-0.12 in the PLA stent group and 0.78+/-0.39 in the controls. In the PLA stent group, the mean inflammation score was 1.46+/-0.78 compared to 0.58+/-0.40 in the control group. There were no differences observed between the animal models. CONCLUSIONS: The PLA stent showed increased neointimal formation and reduced patency during early follow-up. Mechanical properties of the new biodegradable vascular stents are still inadequate, and the stent and the delivery device require modifications. The study methods were assessed as reliable and reproducible.

Animals↗

PubMed1995

Biodegradable microspheres in drug delivery.

General aspects of biodegradable microspheres prepared from natural and synthesized polymers used in drug delivery systems are reviewed first from various viewpoints: characteristics of biodegradable polymers (physicochemical properties, bioerosion mechanism, biocompatibility), preparation method for the microspheres, drug release from parenteral products and briefly nonparenteral products. The relationship between release pattern and pharmacological activity of therapeutic peptides and proteins and rational controlled release design are also discussed. In the latter half, successful sustained release depot formulations of peptides, leuprorelin acetate, and thyrotropin-releasing hormone (TRH), utilizing poly(lactic acid) (PLA) and poly(lactic/glycolic acid) (PLGA) microspheres are reviewed with respect to preparation, drug release, biocompatibility, pharmacological effects, and results of clinical studies. Thereafter, studies on antitumor therapy by chemoembolization using PLGA microspheres containing an angiogenesis inhibitor (TNP-470) are described as an example of targeted drug delivery with biodegradable microspheres.

Animals↗

PubMed2005

Biodegradation of crude oil by Pseudomonas aeruginosa in the presence of rhamnolipids.

The potential biodegradation of crude oil was assessed based on the development of a fermentative process with a strain of Pseudomonas aeruginosa which produced 15.4 g/L rhamnolipids when cultured in a basal mineral medium using glycerol as a sole carbon source. However, neither cell growth nor rhamnolipid production was observed in the comparative culture system using crude oil as the sole carbon source instead. As rhamnolipid, an effective biosurfactant, has been reported to stimulate the biodegradation of hydrocarbons, 1 g/L glycerol or 0.22 g/L rhamnolipid was initially added into the medium to facilitate the biodegradation of crude oil. In both situations, more than 58% of crude oil was degraded and further converted into accumulated cell biomass and rhamnolipids. These results suggest that Pseudomonas aeruginosa could degrade most of crude oil with direct or indirect addition of rhamnolipid. And this conclusion was further supported by another adsorption experiment, where the adsorption capacity of crude oil by killed cell biomass was negligible in comparison with the biologic activities of live cell biomass.

Biodegradation, Environmental↗

PubMed2004

Enhancing the attenuation of explosives in surface soils at military facilities: combined sorption and biodegradation.

This research evaluated soil amendments designed to enhance the adsorption and biodegradation of explosives at military training facilities, thus minimizing their potential for transport to subsurface environments. Several carbon cosubstrates were tested in soil slurries for their ability to stimulate the biodegradation of 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (royal demolition exposive [RDX]), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (high-melting explosive [HMX]) by indigenous soil microorganisms. Crude soybean oil and molasses stimulated mineralization of RDX (30-40%) and HMX (approximately 10%). The TNT was not significantly mineralized in any of the treatments, but high-performance liquid chromatography (HPLC) analysis indicated extensive transformation of TNT to amino-containing compounds. The biodegradation of explosives was then examined in unsaturated soil microcosms amended with crude soybean oil and molasses combined with sphagnum peat moss and sawdust. Minimal TNT mineralization was observed, and HMX mineralization was only observed with molasses addition. In contrast, RDX mineralization was extensive in microcosms amended with soybean oil or molasses. The presence of peat moss decreased soybean oil-stimulated RDX mineralization by approximately 5%, but resulted in about 5% greater RDX mineralization compared with molasses only. Sawdust markedly decreased mineralization regardless of cosubstrate type. Mass balance results indicated that the formation of bound residues likely was occurring, especially for TNT. These results indicate that the application of inexpensive adsorbents and cosubstrates to soils may significantly improve the protection of groundwater resources underlying live fire ranges.

Adsorption↗

PubMed2004

Multiple mechanisms contribute to the biodegradation of benzo[a]pyrene by petroleum-derived multicomponent nonaqueous-phase liquids.

The presence of multicomponent nonaqueous-phase liquids (NAPLs) on contaminated sites critically alters the biodegradation susceptibility of many target pollutants, including polycyclic aromatic hydrocarbons. This study investigated the effects of petroleum-derived multicomponent NAPLs on biodegradation of benzo[a]pyrene by a bacterial consortium in liquid culture. When high-boiling point diesel fuel distillate (HBD)-NAPL was added to liquid culture, the consortium initiated benzo[a]pyrene mineralization after a lag period of several days. This lag period was not observed in the mineralization of phenanthrene, anthracene, and chrysene by the same consortium with HBD. Nonaqueous-phase liquids added to cultures pregrown before experimentation largely affected the extent of benzo[a]pyrene mineralization and the duration of lag period in subsequent experiments, suggesting that NAPL presence was important for maintaining the efficiency of the mineralizing consortium. Experiments using further fractionated oil components suggested that stimulation of benzo[a]pyrene mineralization by NAPLs was fraction dependent; an alkylated aromatic fraction was more effective than aromatic and aliphatic fractions. The effect of NAPL on benzo[a]pyrene biodegradation was determined to be multimechanistic; that is, NAPL acted as a cosolvent for polycyclic aromatic hydrocarbon dissolution, as a substrate to induce cometabolic degradative pathways, and as an agent to formulate the effective microbial consortium. Data suggest that the third mechanism was of particular importance for rapid benzo[a]pyrene mineralization.

Benzo(a)pyrene↗

PubMed2004

Bacterial energetics, stoichiometry, and kinetic modeling of 2,4-dinitrotoluene biodegradation in a batch respirometer.

A stoichiometric equation and kinetic model were developed and validated using experimental data from batch respirometer studies on the biodegradation of 2,4-dinitrotoluene (DNT). The stoichiometric equation integrates bacterial energetics and is revised from that in a previous study by including the mass balance of phosphorus (P) in the biomass. Stoichiometric results on O2 consumption, CO2 evolution, and nitrite evolution are in good agreement with respirometer data. However, the optimal P requirement is significantly higher than the stoichiometrically derived P, implying potentially limited bioavailability of P and the need for buffering capacity in the media to mitigate the adverse pH effect for optimal growth of DNT-degrading bacteria. An array of models was evaluated to fit the O2/CO2 data acquired experimentally and the DNT depletion data calculated from derived stoichiometric coefficients and cell yield. The deterministic, integrated Monod model provides the goodness of fit to the test data on DNT depletion, and the Monod model parameters (Ks, X0, mumax, and Y) were estimated by nonlinear regression. Further analyses with an equilibrium model (MINTEQ) indicate the interrelated nature of medium chemical compositions in controlling the rate and extent of DNT biodegradation. Results from the present batch respirometer study help to unravel some key factors in controlling DNT biodegradation in complex remediation systems, in particular the interactions between acidogenic DNT bacteria and various parameters, including pH and P, the latter of which could serve as a nutrient, a buffer, and a controlling factor on the bioavailable fractions of minerals (Ca, Fe, Zn, and Mo) in the medium.

Aerobiosis↗

PubMed2005

A new biodegradation prediction model specific to petroleum hydrocarbons.

A new predictive model for determining quantitative primary biodegradation half-lives of individual petroleum hydrocarbons has been developed. This model uses a fragment-based approach similar to that of several other biodegradation models, such as those within the Biodegradation Probability Program (BIOWIN) estimation program. In the present study, a half-life in days is estimated using multiple linear regression against counts of 31 distinct molecular fragments. The model was developed using a data set consisting of 175 compounds with environmentally relevant experimental data that was divided into training and validation sets. The original fragments from the Ministry of International Trade and Industry BIOWIN model were used initially as structural descriptors and additional fragments were then added to better describe the ring systems found in petroleum hydrocarbons and to adjust for nonlinearity within the experimental data. The training and validation sets had r2 values of 0.91 and 0.81, respectively.

Biodegradation, Environmental↗

PubMed2005

The prestige oil spill. I. Biodegradation of a heavy fuel oil under simulated conditions.

In vitro biodegradation of the Prestige heavy fuel oil has been carried out using two microbial consortia obtained by enrichment in different substrates to simulate its environmental fate and potential utility for bioremediation. Different conditions, such as incubation time (i.e., 20 or 40 d), oil weathering, and addition of an oleophilic fertilizer (S200), were evaluated. Weathering slowed down the degradation of the fuel oil, probably because of the loss of lower and more labile components, but the addition of S200 enhanced significantly the extension of the biodegradation. n-Alkanes, alkylcyclohexanes, alkylbenzenes, and the two- to three-ring polycyclic aromatic hydrocarbons (PAHs) were degraded in 20 or 40 d of incubation of the original oil, whereas the biodegradation efficiency decreased for higher PAHs and with the increase of alkylation. Molecular markers were degraded according to the following sequence: Acyclic isoprenoids > diasteranes > C27-steranes > betabeta-steranes > homohopanes > monoaromatic steranes > triaromatic steranes. Isomeric selectivity was observed within the C1- and C2-phenanthrenes, dibenzothiophenes, pyrenes, and chrysenes, providing source and weathering indices for the characterization of the heavy oil spill. Acyclic isoprenoids, C27-steranes, C1- and C2-naphthalenes, phenanthrenes, and dibenzothiophenes were degraded completely when S200 was used. The ratios of the C2- and C3-alkyl homologues of fluoranthene/pyrene and chrysene/benzo[a]anthracene are proposed as source ratios in moderately degraded oils. The 4-methylpyrene and 3-methylchrysene were refractory enough to serve as conserved internal markers in assessing the degradation of the aromatic fraction in a manner similar to that of hopane, as used for the aliphatic fraction.

Alkanes↗

PubMed2001

2,4-Toluene diamines--their carcinogenicity, biodegradation, analytical techniques and an approach towards development of biosensors.

2,4-Toluene diamine (TDA), a class A carcinogen, is a major raw material for the production of toluene diisocyanate (TDI), which is one of the precursors for the production of polyurethane foams (PU). This review deals with 2,4-toluene diamine's (TDA) carcinogenicity, analytical techniques, biodegradation and use as a biosensor for biogenic and synthetic amines, emphasizing various carcinogenicity studies by 2,4-TDA on animals and humans. This review reports some publications of the analysis of body fluid samples of workers from a PU producing factory for presence of TDA and TDI, since TDI gets absorbed into the worker's body, getting metabolized into TDA. Biodegradations of 2,4-TDA by various researchers are reported and also our own research experience with biodegradation of 2,4-TDA using Aspergillus nidulans isolated from soil site at a polyurethane foam dumping site have been discussed in this review. Biosensors for various biogenic and synthetic amines are discussed.

Animals↗

PubMedDate not supplied

Transport and biodegradation of perchlorate in soils.

Perchlorate (ClO4-) contamination of ground water and surface water is a widespread problem, particularly in the western United States. This study examined the effect of biodegradation on perchlorate fate and transport in soils. Solute transport experiments were conducted on two surface soils. Pulses of solution containing perchlorate and Br- were applied to saturated soil columns at steady state water flow. Perchlorate behaved like a nonreactive tracer in Columbia loam (coarse-loamy, mixed, superactive, nonacid, thermic Oxyaquic Xerofluvent) but was degraded in Yolo loam (fine-silty, mixed, superactive, nonacid, thermic Mollic Xerofluvent). Batch experiments demonstrated that perchlorate removal from solution in Yolo loam was caused by biodegradation. Other batch experiments with Yolo loam surface and subsurface soils, Columbia loam surface soil, and dredge tailings demonstrated that perchlorate biodegradation required anaerobic conditions, an adequate carbon source, and an active perchlorate-degrading microbial population. The sequential reduction of perchlorate and NO3- by an indigenous soil microbial community in Yolo loam batch systems was also studied. Nitrate reduction occurred much sooner than perchlorate reduction in soils that had not been previously exposed to perchlorate, but NO3- and perchlorate were simultaneously reduced in soils previously exposed to perchlorate. The results of this study have implications for in situ remediation schemes and for agricultural soils that have been contaminated by perchlorate-tainted irrigation water.

Biodegradation, Environmental↗

PubMedDate not supplied

Effects of oxygen on anoxic biodegradation of benzoate during continuous culture.

In this study, various amounts of oxygen were added to denitrifying chemostats receiving benzoate to mimic the input of oxygen to anoxic zones of biological nutrient removal systems. The effect of oxygen on the biodegradative capability of the mixed-microbial culture for benzoate was investigated. The anoxic benzoate biodegradative capability of the culture was not significantly changed as the mass flowrate of oxygen was increased to 40% of the input benzoate chemical oxygen demand (COD) mass flowrate, but was decreased approximately 70% when the mass flowrate of oxygen was increased to 70% of the input benzoate COD mass flowrate. The decrease in the anoxic benzoate biodegradative capability was due primarily to the loss of the denitrifying enzymes (measured by the anoxic pyruvate-degrading ability) and not to the loss of the key anoxic catabolic enzyme (benzoyl-coenzyme A reductase). The proportional increase in the concentration of nitrate as the residual terminal electron acceptor and the lack of synthesis of aerobic ring-cleavage enzymes as the oxygen input to the chemostat was increased suggest that the mixed microbial culture preferred oxygen to nitrate as the terminal electron acceptor, but degraded benzoate using the anoxic metabolic pathway. The concentration of the mixed microbial culture increased as the oxygen input to the chemostat was increased, suggesting that the oxygen was used by cytochrome cbb3 rather than quinol oxidase because the energetic yield of cytochrome cbb3 is higher than that of quinol oxidase or the nitrogen oxide reductases.

Anti-Infective Agents↗

PubMed1983

Slow release of insulin from a biodegradable matrix implanted in diabetic rats.

This report describes the development of a long-acting insulin accomplished by the slow release of hormone from an implantable, biodegradable matrix. Rats made diabetic with streptozotocin received a single subcutaneous implant of insulin-albumin microbeads that released biologically active insulin for periods up to 3 wk. The mean fasting blood glucose level for treated animals was 88 mg/dl as compared with 392 mg/dl for untreated diabetic controls. With a mean starting body weight of 187 g, treated animals gained weight reaching a mean weight of 228 g; in contrast, untreated animals lost weight to a mean of 175 g. When insulin-albumin microbeads were periodically implanted and removed, lower blood glucose levels were only associated with the presence of the implants. The microbead implants biodegraded in 4-8 wk, thus obviating the need for surgical removal. These results suggest that a long-acting insulin may be produced by the entrapment of insulin within a biodegradable matrix.

Animals↗

PubMedDate not supplied

In vitro biodegradation of polyhydroxybutyrate-hydroxyvalerate microcapsules exposed to Hank's buffer, newborn calf serum, pancreatin and synthetic gastric juice.

Spherical microporous reservoir-type microcapsules, fabricated using a W/O/W double emulsion technique with solvent evaporation and composed of 330 kD poly(beta-hydroxybutyrate-hydroxyvalerate (P(HB-HV)) (10.8% HV)/20% PCL II containing a range of bovine serum albumin (BSA) loadings, were incubated in Hank's buffer, pH 7.4, newborn calf serum (NCS), 1.5% pancreatin and synthetic gastric juice containing 10% pepsin over 30 days, and their percentage weight loss (PWL) and change in ultrastructural morphology monitored by gravimetry and stereoscan electron microscopy (SEM), respectively. The greatest percentage weight loss from microcapsules was observed after incubation in NCS and decreased in the other NCS > pancreatin > synthetic gastric juice > Hank's buffer. Only 5, 10 and 15% bovine serum albumin (BSA) loaded microcapsules incubated in Hank's buffer and synthetic gastric juice showed a significant increase in PWL with increasing percentage BSA loading. The overall sequence of changes in structural morphology due to biodegradation occurred at different rates in the different 'physiological' media. An initial increase in micropore diameter was followed by the coalescence of microspores to form macroporous pits (Hank's buffer). Further biodegradation in NCS, pancreatin and synthetic juice was characterized by significant surface and bulk erosion. Only in pancreatin and NCS did biodegradation proceed to a loss of spherical shape and partial (pancreatin) and almost total (NCS) disruption of microcapsule structure after 30 days.

Animals↗

PubMed1982

Insulin-albumin microbeads: an implantable, biodegradable system.

A feasibility study on developing an implantable, biodegradable insulin delivery system was carried out. Insulin-albumin microbeads (50-1,000 microns diameter) were implanted in diabetic rats. After a single subcutaneous implant of the glutaraldehyde crosslinked microbeads, elevated blood-insulin levels were detected in the diabetic animals for longer than two months. While the blood-insulin levels of the treated animals were sustained between 10 and 67 microU/ml during the initial two month post-implantation period, complete in-vivo biodegradation of the microbeads took longer than five months. The diabetic animals, with the insulin-albumin microbead implants, gained weight. In contrast, untreated diabetic controls lost weight. Fibrous capsules were found to have surrounded the microbeads when the implants were recovered at one and two months post-implantation. The results suggest that the fibrous capsules played a role in retarding insulin release from the albumin microbead system. Cross-linked serum albumin microbeads have the clinical potential of providing long-term in-vivo drug release. This system has the additional advantage of being biodegradable and also provides more options for the method and site of implantation.

Animals↗

PubMed1989

Segmental neogenesis of the dog esophagus utilizing a biodegradable polymer framework.

This study evaluated the ability of biodegradable implants fabricated from polymers and co-polymers of polylactic acid (PLA) and polyglycolic acid (PGA) to induce regeneration of surgically created defects in the dog esophagus. The study utilized 12 mongrel dogs that had a 5 cm segment of the esophagus removed. Implants were fabricated by spray casting the polymers on a spinning Teflon mandril. The defects were repaired by suturing the biodegradable implants to the proximal and distal ends of the esophagus. Ten of the dogs were sacrificed from 3 days to 8 weeks after surgery while 1 of the dogs died after 3 years and 1 dog was sacrificed 4 years after graft placement. Endoscopic and histologic examination of the grafts 3 days after placement showed minimal inflammatory response and an apparent seal between the esophagus and implant at the suture lines. Two weeks after surgery a fibrous connective tissue sheath, continuous with the proximal and distal segments of the esophagus, could be seen surrounding the graft. One month after placement, the implants were partially degraded leaving a connective tissue repair continuous with the proximal and distal ends of the esophagus. The repair area was lined with epithelium and enabled the dogs to drink freely and eat semisolid foods. In conclusion, it has been shown that it is possible to fabricate a biodegradable implant which can stimulate regeneration of a hollow organ and which is compatible with long term survival.

Animals↗

PubMed1993

Arthrodesis of the first metatarsophalangeal joint in rheumatoid arthritis. Biodegradable rods and Kirschner-wires in 39 cases.

The first metatarsophalangeal joint was arthrodesed in 39 patients with rheumatoid arthritis. Fixation material was either biodegradable self-reinforced poly-L-lactide rods or Kirschner-wires. There were 3 clinical nonunions in the biodegradable group, and none in the K-wire group, and radiographic nonunion in 5 and 2 cases, respectively. The fixator had to be removed in 3 cases in the K-wire group. The biodegradable rods did not seem to be any better than K-wires.

Adult↗

PubMed2000

Biodegradable poly (lactic acid) microspheres for drug delivery systems.

In connection with aim of maximizing the bio-availability of conventional drugs with minimum side-effects, new drug delivery systems (DDS) continue to attracted much attention. The controlled or sustained release of drugs represents one such approach, and in this regard report upon a study of DDS using biodegradable polymers which include poly (lactic acid) (PLA), poly (glycolic acid), and their copolymers (PLGA). Much attention is being paid to the controlled release of bio-active agents from microcapsules and microspheres made of biodegradable polymers, such as lactic acid homopolymers, as well as copolymers of glycolic acid. (11-21) Microcapsules or microspheres are injectable and able to provide pre-programmed durations of action, offering several advantages over the conventional dosage forms. This article reviews the results of a work program conducted in collaboration with a medical doctor upon DDS using biodegradable microspheres, such as PLA and PLGA.

Animals↗

PubMed1997

Repair of soft tissue to bone using a biodegradable suture anchor.

The medial collateral ligaments of 18 New Zealand rabbits were surgically detached from bone. In one knee, the ligament was repaired using a biodegradable suture anchor composed of a co-polymer of lactic and glycolic acid. The contralateral medial collateral ligament was not repaired. Animals were sacrificed at 4, 8, and 12 weeks after the operation, and the knee that had the ligament repair was compared with the contralateral control knee. All knees were tested manually tested for stability to valgus stress and then prepared for histologic examination. Medial collateral ligaments repaired using the biodegradable suture anchor demonstrated stability to valgus stress and anatomic healing at the bone-tendon junction. Resorption of the implant was virtually complete by 12 weeks. All specimens demonstrated less inflammatory reaction to the suture anchor than to the attached Vicryl suture. This contrasts with the control group, which was grossly unstable and demonstrated scarring in this nonanatomic position. These results demonstrate efficacy of this particular material of biodegradable implant and justify further investigative efforts.

Animals↗