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Severe aseptic synovitis of the knee after biodegradable internal fixation. A case report.

Biodegradable rods made of polyglycolide (Dexon, Biofix) or lactide-glycolide copolymer (Vicryl) have been used for the past 5 years for internal fixation of a variety of fractures and osteotomies (Böstman et al. 1989, 1990b). Experience from using such rods for fixation of intraarticular osteochondral lesions seems to be less extensive. We report a case of severe synovial reaction to biodegradable rods used for fixation of osteochondritis dissecans of the knee and discuss possible reasons for the increased risk of foreign-body reactions when these rods are used intraarticularly.

Adult↗

Malleolar fractures in alcoholics treated with biodegradable internal fixation. 6/16 reoperations in a randomized study.

29 alcohol abusers with displaced malleolar fractures were randomized to treatment with biodegradable self-reinforced polyglycolide screws or metallic implants. During an average follow-up time of 7 (0-15) months, 8 patients out of 16 treated with biodegradable fixation had postoperative redisplacement of the fracture and 6 were reoperated. 1 fracture in 13 patients with metallic fixation had a slight displacement postoperatively which did not require reoperation.

Adult↗

Comparison of biodegradable and metallic tension-band fixation for patella fractures. 38 patients followed for 2 years.

We compared the outcome of patella fractures fixed by biodegradable tension-band (B) with self-reinforced polyglycolide or self-reinforced poly-L-lactide plugs and polyester ligaments or by metallic tension-band (M) with Kirschner wires and metallic cerclage wire in a randomized study. 38 fractures (18 with B and 20 with M) were treated. The follow-up time was 24 (14-32) months. The fractures healed in all patients after a medium of 8 weeks. In the B group, the clinical outcome was good in 13, fair in 4, and poor in 1 patient. In the M group, the corresponding figures were 15, 3 and 2. There were no clinical or radiographic differences between the two methods. Patella fractures can be treated, successfully using biodegradable tension-band fixation with no need for a second operation to remove the implants after bone union.

Absorption↗

Potential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogels for skull bone regeneration.

Biodegradable gelatin hydrogels incorporating basic fibroblast growth factor (bFGF) were evaluated for their efficacy in bone regeneration using a rabbit model. Hydrogels with water contents of 85% and 98% were prepared using chemical crosslinking of gelatin with an isoelectric point of 4.9 in aqueous solution and, after freeze drying, were impregnated with an aqueous solution of bFGF to obtain bFGF-incorporated gelatin hydrogels. When they were implanted into bone defects measuring 6 mm in diameter in rabbit skulls (six animals/group), complete closure of the defect was observed at 12 weeks after implantation, regardless of the water content of the hydrogels. In contrast, bFGF did not enhance bone regeneration when applied to the skull defect in solution with phosphate-buffered saline (PBS). Also, gelatin hydrogels lacking bFGF were not effective in inducing bone formation, with fibrous tissue growing into the defect instead, similar to the skull defect seen in control rabbits treated with PBS. This indicates that the presence of hydrogels did not interfere with bone regeneration at the skull defect, probably because of their disappearance during biodegradation. It is concluded that the gelatin hydrogel is a promising matrix for effective induction of biological activity of bFGF for bone regeneration in skull and sinus defects.

Animals↗

Biodegradability and microbial activities during composting of poultry litter.

Poultry litter is composted to reduce odor and pathogens and to improve its quality as a soil amendment. Organic material, e.g., sawdust, is added to increase the C:N ratio to achieve optimum degradation of organic C and retention of N through microbial biomass formation. However, the relative biodegradabilities of the organic material in poultry litter and the amendment are usually not known. Furthermore, it is assumed that as microorganisms metabolize organic compounds and produce CO2, they increase in biomass and, therefore, retain N. In this study, bench-scale compost reactors were used to determine the relative contributions of poultry litter and of the amendment (sawdust) to the biodegradability of a compost mix. Approximately 29% of the volatiles lost from the poultry litter mix came from the sawdust. Fiber analyses revealed that only a small portion of cellulose was degraded. Although microbial subpopulations able to degrade selected macromolecules were present at varying levels, the overall level of microorganisms did not change markedly. Populations capable of degrading bacterial cell walls were present throughout the composting period, and microbiological assays indicated that inorganic nutrients were available to support limited microbial growth. These results suggest that N compounds and inorganic nutrients are recycled, rather than fixed during composting.

Animals↗

Broad-spectrum biodegradation of aliphatic and aliphatic-aromatic polyesters by Papiliotrema laurentii isolated from locust frass.

Biodegradable aliphatic and aliphatic-aromatic polyesters, such as poly(butylene adipate-co-terephthalate) (PBAT), polylactic acid (PLA), polycaprolactone (PCL), polybutylene succinate (PBS), and polyhydroxyalkanoates (PHA), are increasingly used as sustainable alternatives to petrochemical plastics. However, their depolymerization outside industrial composting facilities is often incomplete. This study characterized Papiliotrema laurentii strain 62UF-13, isolated from migratory locust frass, for broad-spectrum polyester hydrolysis. Emulsion assays demonstrated hydrolytic activity across all five polymers, with PCL and PBS showing the highest clearance rates. Solid-film assays revealed substantial gravimetric mass loss of PCL, PLA, and PHA cast films, whereas a commercial PBAT-PLA mulch film in minimal medium, underwent progressive fragmentation/disintegration, as assessed by the remaining film area. Incubation with the PBAT-PLA film was accompanied by the release of adipic acid (49.60 mg/L, week 1) and terephthalic acid (maximum 21.62 mg/L, week 4), followed by a decrease to 0.26 mg/L by week 8, coinciding with the emergence of putative 3,4-dihydroxymandelic acid and a putative acetylated derivative. Scanning electron microscopy (SEM) revealed pronounced pitting and erosion, while Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) indicated ester-bond scission and changes in crystallinity/melting behavior. Whole-genome sequencing identified eight candidate polyesterases, including cutinases and esterases, with ≥ 60% amino acid identity to known hydrolases active on PCL, PBS, PHA, and PLA. This study is the first report of P. laurentii degrading a broad range of aliphatic and aliphatic-aromatic polyesters, including partial biotransformation of terephthalate moieties from PBAT. Integration of phenotypic assays and genomic evidence positions P. laurentii 62UF-13 as a viable biocatalyst for decentralized management of biodegradable plastic waste under mild environmental conditions.

Papiliotrema laurentii↗

Development of composite porous scaffolds based on collagen and biodegradable poly(ester urethane)urea.

Our objective in this work was to develop a flexible, biodegradable scaffold for cell transplantation that would incorporate a synthetic component for strength and flexibility and type I collagen for enzymatic lability and cytocompatibility. A biodegradable poly(ester urethane)urea was synthesized from poly(caprolactone), 1,4-diisocyanatobutane, and putrescine. Using a thermally induced phase separation process, porous scaffolds were created from a mixture containing this polyurethane and 0%, 10%, 20%, or 30% type I collagen. The resulting scaffolds were found to have open, interconnected pores (from 7 to >100 um) and porosities from 58% to 86% depending on the polyurethane/collagen ratio. The scaffolds were also flexible with breaking strains of 82-443% and tensile strengths of 0.97-4.11 MPa depending on preparation conditions. Scaffold degradation was significantly increased when collagenase was introduced into an incubating buffer in a manner that was dependent on the mass fraction of collagen present in the scaffold. Mass losses could be varied from 15% to 59% over 8 weeks. When culturing umbilical artery smooth muscle cells on these scaffolds higher cell numbers were observed over a 4-week culture period in scaffolds containing collagen. In summary, a strong and flexible scaffold system has been developed that can degrade by both hydrolysis and collagenase degradation pathways, as well as support cell growth. This scaffold possesses properties that would make it attractive for future use in soft tissue applications where such mechanical and biological features would be advantageous.

Animals↗

Using biodegradable polymers in advanced drug delivery systems.

Research currently is under way to design novel drug delivery systems that enhance the duration of activity and that provide site-specific release of the drug. Biodegradable polymers represent an important class of materials used in the manufacture of these systems. This article discusses some major types of biodegradable polymers and reviews their applications in advanced drug delivery.

Biodegradation, Environmental↗

Development of a biodegradable antibiotic delivery system.

Antibiotic beads have been used as a drug delivery system for the treatment of various surgical infections. In this study, the copolymer 50:50 poly(DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form five types of biodegradable antibiotic beads. The beads were placed in 1 mL of phosphate buffered saline and incubated at 37 degrees C. The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days. The release was most marked during the first 48 hours. All copolymer 50:50 poly(DI lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks). The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100%. Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method. The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads. This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients.

Absorbable Implants↗

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.

BACKGROUND: The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS: Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). RESULTS: 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. CONCLUSIONS: This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].

Adolescent↗

Developing new methods for the treatment of malignant brain tumours: local delivery of anti-neoplastic agents using biodegradable polymers.

Controlled delivery of chemotherapeutic agents by biodegradable polymers is a new strategy that has been added to the arsenal available for the treatment of malignant neoplasms. This approach is particularly suitable for the management of brain tumours because of the constraints imposed by the blood brain barrier (BBB). The use of polymers for local drug delivery minimises systemic toxicity, while achieving prolonged elevation of intratumoural drug concentrations that results in improved efficacy. In addition, this strategy broadens the spectrum of drugs available for the treatment of neoplasms in the central nervous system to include agents whose efficacy is significantly limited by systemic toxicity or inability to penetrate the BBB. In this review, we discuss the rationale and background for the use of this novel approach. We also summarise the clinical trials and laboratory investigations leading to the development of local delivery of anti-neoplastic agents from biodegradable polymers for the treatment of malignant gliomas.

Animals↗

TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function.

BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle fabrication and after growth factor release. At an optimal TGF-beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells over 21 days of culture, with increased total cell number, alkaline phosphatase activity, and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor enhances marrow stromal cell proliferation and osteoblastic differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1 from PLGA/PEG microparticles is representative of emerging tissue engineering technologies that may modulate cellular responses to encourage bone regeneration at a skeletal defect site.

Animals↗

Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone.

BACKGROUND: Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. Collagen from animal sources has previously been the preferred carrier material in animal experiments. More recently, synthetic biodegradable polymers have been tested as a delivery vehicle for osteoinductive agents. In earlier studies performed in our laboratory, it was found that the polylactic acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery systems. METHODS: To obtain new PLA-PEG polymers that exhibit greater plasticity, the molecular sizes of PLA and PEG segments in the copolymer chains were increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650-PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral density (BMD) of the ectopic new bone were measured by means of single energy X-ray absorptiometry (SXA). RESULTS: All of the PLA6,500-PEG3,000 implants with 10 or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control implants that lacked rhBMP-2 did not show new bone formation. Radiographic and histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2 harvested 3 weeks after implantation had normal bone characteristics with hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2 were significantly higher than those obtained with the liquid PLA650-PEG200 polymers (p < 0.001 for each of the three values). CONCLUSIONS: These results indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works effectively as a BMP delivery system. These data suggest that the total molecular size and ratio of PLA size to PEG size is an essential factor in determining the efficacy of a BMP delivery system. After implantation, it is possible that the PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen, resulting in bone formation that exceeded the size of the original implants. This expansion characteristic is a potentially beneficial property, given the intended practical application of the polymer in the repair of bone defects. CLINICAL RELEVANCE: New synthetic biodegradable delivery systems will play an important role in the clinical applications of rhBMPs in which local formation of bone via an osteoinductive graft material is needed. Further pre-clinical and clinical work is necessary to establish the safety of these implants before they are adopted for widespread clinical use.

Animals↗

Aerobic biodegradation of gasoline oxygenates MTBE and TBA.

MTBE degradation was investigated using a continuously stirred tank reactor (CSTR) with biomass retention (porous pot reactor) operated under aerobic conditions. MTBE was fed to the reactor at an influent concentration of 150 mg/l (1.70 mmol/l). A second identical reactor was operated as a control under the same conditions with the addition of 2.66 g/l of sodium azide, to kill any biological activity. Results from these experiments suggest that biomass retention is critical to the degradation of MTBE. The rate of MTBE removal was shown to be related to the VSS concentration. MTBE removal exceeded 99.99% when the VSS concentration in the reactor was over 600 mg/l. Results obtained from batch experiments conducted on mixed liquor samples from the porous pot reactor indicate that the individual rates of biodegradation of MTBE and TBA were higher for initial concentrations of 15 mg/l than for concentrations of 5 mg/l. The presence of TBA at lower concentrations did not effect the rate of MTBE degradation, however higher concentrations of TBA did reduce the rate of biodegradation of MTBE. Denaturing Gradient Gel Electrophoresis (DGGE) analysis reveals that the culture consisted of a community of bacterial organisms of about 6 species.

Bacteria, Aerobic↗

Removal of chlorinated pollutants by a combination of ultrasound and biodegradation.

Chlorinated organic compounds are hazardous pollutants found in waste water, surface water, and ground water. Our study shows that a combination of ultrasonic pretreatment and biodegradation effectively removes the solvent chlorobenzene and the disinfectant 2,4-dichlorophenol, also reduces Adsorbable Organic Halogens (AOX) and Chemical Oxygen Demand (COD). In our experiments, the ultrasonic dechlorination was not influenced by the presence of other soluble organic compounds like acetate or glucose. Dechlorination of chlorobenzene by ultrasound did not lead to toxic or inhibiting reaction products. More than that, the ultrasonic pretreatment significantly reduced the toxicity of 2,4-dichlorophenol and biological activity was initiated after sonication. Residual organic pollutants after ultrasonic pretreatment were eliminated by biodegradation.

Anthelmintics↗

Identification of hydroxylamino-dinitroso-1,3,5-triazine as a transient intermediate formed during the anaerobic biodegradation of hexahydro-1,3,5-trinitro-1,3,5-triazine.

The metabolic fate of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in a mixed culture incubated under methanogenic conditions was studied. Analysis by high-performance liquid chromatography (HPLC) confirmed the loss of RDX and the formation of mono-, di-, and trinitroso-RDX as transient biodegradation intermediates. An additional peak observed in the HPLC chromatograms was identified by liquid chromatography-mass spectrometry as hydroxylamino-dinitroso-1,3,5-triazine. This is the first report identifying hydroxylamino-dinitroso-1,3,5-triazine as a transient intermediate produced during the anaerobic biodegradation of RDX.

Bacteria, Anaerobic↗

Wastewater COD characterization: biodegradability of physico-chemical fractions.

Physico-chemical and biological characterization methods were applied to wastewater samples originating from 7 French WWTPs. The settleable fraction (S), unsettleable-coagulable fraction (US-C) and unsettleable-uncoagulable fraction (US-UC) were separated. Special emphasis was put on the determination of hydrolysis kinetics associated with coagulable- and settleable-fractions in order to model their behaviour in activated sludge processes, as both these fractions are influenced by the SRT. The "soluble" fraction (i.e. US-UC) was composed of readily biodegradable COD (2 to 27%), readily hydrolysable COD (37 to 90%) and inerts (2 to 47%). The "colloidal" fraction (i.e. US-C) was composed of heterotrophic biomass (9 to 24%) and readily hydrolysable COD (6 to 82%), with the rest being inerts or very slowly biodegradable COD (0 to 70%). The "particulate" fraction (i.e. settleable) was composed of biomass (14 +/- 6%), readily hydrolysable COD (21 +/- 14%), slowly hydrolysable COD (about 45-50%) and 15 to 20% which can be considered as inert matter (X(I)). "Readily hydrolysable COD" was correctly modeled by a global first-order reaction. First-order constants (KH) were 9 +/- 2 d(-1) for raw-wastewater, 12 +/- 3 d(-1) for primary settled-wastewater and 16 +/- 5 d(-1) for coagulated-wastewater. "Slowly hydrolysable COD" was correctly modeled by a limited surface reaction. Concerning this fraction, the specific hydrolysis rate (kH) ranged from 0.25 to 1.05 d(-1), and the affinity constant (K(X)) ranged from 0.33 to 0.95 gCOD/gCOD based on settleable solids analysis.

Biodegradation, Environmental↗

[The biodegradation of poly-beta-hydroxybutyrate (PHB) by a model soil community: the effect of cultivation conditions on the degradation rate and the physicochemical characteristics of PHB].

The biodegradation of films made of poly-beta-hydroxybutyrate (PHB) with a molecular mass of 1500 kDa was studied using a model soil community in the presence and absence of nitrate and at different concentrations of oxygen in the gas phase. The biodegradation of PHB was investigated with respect to changes in its molecular mass, crystallinity, and some mechanical properties.

Biodegradation, Environmental↗