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A biodegradable electrical bioconductor made of polypyrrole nanoparticle/poly(D,L-lactide) composite: A preliminary in vitro biostability study.

The electrical stability of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite was studied in vitro and compared with that of PPy-coated polyester fabrics. Specimens were incubated in Ringer's solution at 37 degrees C for up to 8 weeks with or without the circulation of DC current under a constant 100 mV voltage. In situ current variation with incubation time was recorded. The AC volume electrical conductivity of the specimens before and after incubation in phosphate-buffered saline was recorded using a frequency analyzer. Water absorption and weight loss were monitored metrologically. Changes in the oxidation state of incubated PPy were analyzed with X-ray photoelectron spectroscopy. The morphological changes were observed with scanning electron microscopy, and the glass transition temperature of the PDLLA was investigated using differential scanning calorimetry. The PPy/PDLLA composite in Ringer's solution sustained a relatively stable conductivity up to 8 weeks after an initial period of "conditioning." The PPy-coated fabrics experienced a rapid loss of conductivity when subjected to electrical circulation and regained part of it when disconnected. The volume conductivity of the nonincubated PPy/PDLLA membrane behaved as a typical conductor in the low-frequency range. The mechanisms involved in the various electrical behaviours of the PPy/PDLLA composite and PPy-coated fabrics are discussed. In conclusion, the PPy/PDLLA composite was able to deliver a biologically significant electrical current in a simulated biological solution for up to 8 weeks and therefore may be considered as a first-generation synthetic biodegradable bioconductor.

Biocompatible Materials↗

Human osteoblast cells: isolation, characterization, and growth on polymers for musculoskeletal tissue engineering.

We performed a detailed examination of the isolation, characterization, and growth of human osteoblast cells derived from trabecular bone. We further examined the morphology, phenotypic gene expression, mineralization,and growth of these human osteoblasts on polyester polymers used for musculoskeletal tissue engineering. Polylactic-co-glycolic acid [PLAGA (85:15, 50:50, 75:25)], and poly-lactic acid (L-PLA, D,L-PLA) were examined. The osteoblastic expression of key phenotypic markers osteocalcin, alkaline phosphatase, collagen, and bone sialoprotein at 4 and 8 weeks was examined. Reverse transcription-polymerase chain reaction studies revealed that trabecular-derived osteoblasts were positive for all markers evaluated with higher levels expressed over long-term culture. These cells also revealed mineralization and maturation as evidenced by energy dispersive X-ray analysis and scanning electron microscopy. Growth studies on PLAGA at 50:50,75:25, and 85:15 ratios and PLA in the L and DL isoforms revealed that human osteoblasts actively grew, with significantly higher cell numbers attached to scaffolds composed of PLAGA 50:50 in the short term and PLAGA 85:15 in the long term compared with PLA (p < 0.05). We believe human cell adhesion among these polymeric materials may be dependent on differences in cellular integrin expression and extracellular matrix protein elaboration.

Biocompatible Materials↗

Poly-epsilon-caprolactone/hydroxyapatite composites for bone regeneration: in vitro characterization and human osteoblast response.

Polycaprolactone (PCL), a semicrystalline linear resorbable aliphatic polyester, is a good candidate as a scaffold for bone tissue engineering, due to its biocompatibility and biodegradability. However, the poor mechanical properties of PCL impair its use as scaffold for hard tissue regeneration, unless mechanical reinforcement is provided. To enhance mechanical properties and promote osteoconductivity, hydroxyapatite (HA) particles were added to the PCL matrix: three PCL-based composites with different volume ratio of HA (13%, 20%, and 32%) were studied. Mechanical properties and structure were analysed, along with biocompatibility and osteoconductivity. The addition of HA particles (in particular in the range of 20% and 32%) led to a significant improvement in mechanical performance (e.g., elastic modulus) of scaffold. Saos-2 cells and osteoblasts from human trabecular bone (hOB) retrieved during total hip replacement surgery were seeded onto 3D PCL samples for 1-4 weeks. Following the assessment of cell viability, proliferation, morphology, and ALP release, HA-loaded PCL was found to improve osteoconduction compared to the PCL alone. The results indicated that PCL represents a potential candidate as an efficient substrate for bone substitution through an accurate balance between structural/ mechanical properties of polymer and biological activities.

Alkaline Phosphatase↗

Poly(hexyl-substituted lactides): novel injectable hydrophobic drug delivery systems.

Poly(hexyl-substituted lactides) (PHLA) as new hydrophobic polyesters with controlled molecular weights and narrow distributions were synthesized by ring-opening polymerization (ROP) using tin(II) 2-ethylhexanoate (Sn(Oct)(2)) and benzyl alcohol as catalyst and initiator. Glass transition temperatures (T(g)) and zero shear viscosities (eta(0)) at 25 degrees C could be modulated from T(g)= -42 degrees C to -10 degrees C and 40 to 4850 Pa s, respectively, by varying the polymer molecular weight and the number of hexyl groups along the polymer chain. Degradation studies were performed in terms of both mass and molecular weight loss in the course of time. The degradation mechanism is shown to be of the "bulk erosion" type, and comparable to standard poly(D,L-lactide) (PLA). Despite the increased steric hindrance in the poly(monohexyl-substituted lactide) (PmHLA) due to the hexyl side groups, its degradation rate at pH 7.4 and 37 degrees C was found to be slightly higher than observed for the analogue standard PLA. This could be attributed to the flexible rubbery state of the hexyl-substituted polymer (T(g) approximately -15 degrees C) at the physiological temperature, which is favoring the degradation in comparison to the rigid and glassy standard PLA (T(g) approximately 40 degrees C). In contrast, degradation studies performed at 60 degrees C, where both polymers are above their glass transition temperature, confirmed that the degradation rate is lower for the sterically more hindered PmHLA. The degradation products were analyzed by ESI-MS. Hydrolysis lead first to the corresponding oligo-ester fragments and finally to the nontoxic 2-hydroxyoctanoic acid and lactic acid. Tetracycline was tested as a model drug for release studies. This drug was found to be released faster and in higher amounts in its active form from the PHLA matrix than from standard PLA. The results presented in this work demonstrate the potential of these hydrophobic polylactide-based semisolid materials as an alternative to conventional PLA/PLGA for injectable drug delivery systems.

Anti-Bacterial Agents↗

Composite prostheses used to repair abdominal wall defects: physical or chemical adhesion barriers?

In a composite prosthesis, the component placed at the peritoneal interface takes the form of a physical or chemical barrier. In this experimental study performed on the white New Zealand rabbit, several composites were examined to establish the effectiveness of these barriers at impeding adhesion formation. The biomaterials tested were two polypropylene prostheses (PP) with the physical barriers of expanded polytetrafluoroethylene or polyurethane (PP + ePTFE and PP + PU) and two prostheses (one polyester and the other PP) with the absorbable chemical barriers of polyethylene glycol/glycerol and hyaluronate, respectively (PO + gl and PP + hy). The composites were used to repair 7 x 5 cm defects created in the abdominal wall of the animals by placing the implant in contact with the visceral peritoneum and the subcutaneous tissue and fixing it to recipient tissue by 4/0 polypropylene running suture. Fourteen days after surgery the animals were sacrificed and specimens were taken for light microscopy and scanning electron microscopy. Adhesions developing at the prosthesis/visceral peritoneal interface were quantified. All the prostheses induced optimal mesothelialization. Composites with physical barriers behaved similarly in terms of provoking adhesions. However, the prostheses with chemical barriers differed in their effectiveness at preventing adhesions. Overall, the best results were obtained with the PP + PU composite.

Abdominal Wall↗

Vascular graft infections: in vitro and in vivo investigations of a new vascular graft with long-term protection.

We investigated a polyester vascular prosthesis (PET) coated with elemental silver (SC). Measurement of silver release over a period of 52 weeks by means of inductively coupled plasma atomic emission spectrometry of PET with (PET-G) and without (PET-N) gelatine impregnation revealed a silver release on the first day of 1.2 +/- 0.2 microg (PET-N) and 1.2 +/- 0.1 microg (PET-G) (calculated for 1 g of prosthesis); from the 90th day onward, it was between 0.22 +/- 0.14 microg (PET-N) and 0.18 +/- 0.12 microg (PET-G) per day. The prostheses were incubated with Staphylococcus aureus (S.a.), Staphylococcus epidermidis (S.e.), or Escherichia coli (E.c.) to investigate in vitro antibacterial efficacy. After 6 h of incubation, no colony-forming units were to be seen for any of the bacterial suspensions for PET with SC (p < 0.001). To investigate in vivo antibacterial efficacy, PET-G rings with and without SC contaminated with S.a., S.e., or E.c. were implanted in 18 albino rabbits and examined 7 days after agar culture for 48 h. The silver coating was associated with a significant reduction in bacterial growth (S.a., p = 0.001; S.e., p < 0.005; E.c., p < 0.001). The silver-coated prosthesis, with and without gelatine impregnation, had a significantly antibacterial effect with continuous release of silver.

Animals↗

Role of fluid dynamics on the healing of an in vivo tissue engineered vascular graft.

A polyester (PET) reinforced fibrin-FN-VEGF-TGFbeta vascular graft, formed by a four-step preclotting technique of a porous PET arterial graft, shows the overlapping inflammation, proliferation, and remodeling steps of normal wound healing when implanted in the descending thoracic aorta (DTA) position in the dog, forming a surface layer of endothelial cells. While the DTA grafts readily healed (i.e., endothelialized), similar grafts implanted in the carotid-femoral artery position did not fully heal. Since the initial phases of healing were shown to be dependent upon the transport of blood-borne constituents to the graft surface, the extent of healing appears to be dependent on the fluid dynamics present in the artery-graft-artery construct. The length of the noncompliant graft, the construction of the anastomoses, bends in the construct, graft diameter, and graft compliance can affect the fluid dynamics in the implant, and thus the healing of the graft. This has clinical relevance for the testing and development of new vascular graft materials.

Anastomosis, Surgical↗

Material model measurements and predictions for a random pore poly(epsilon-caprolactone) scaffold.

We investigated material models for a polymeric scaffold used for bone. The material was made by co-extruding poly(epsilon-caprolactone) (PCL), a biodegradable polyester, and poly(ethylene oxide) (PEO). The water soluble PEO was removed resulting in a porous scaffold. The stress-strain curve in compression was fit with a phenomenological model in hyperbolic form. This material model will be useful for designers for quasi-static analysis as it provides a simple form that can easily be used in finite element models. The ASTM D-1621 standard recommends using a secant modulus based on 10% strain. The resulting modulus has a smaller scatter in its value compared with the coefficients of the hyperbolic model, and it is therefore easier to compare differences in material processing and ensure quality of the scaffold. A prediction of the small-strain elastic modulus was constructed from images of the microstructure. Each pixel of the micrographs was represented with a brick finite element and assigned the Young's modulus of bulk PCL or a value of 0 for a pore. A compressive strain was imposed on the model and the resulting stresses were calculated. The elastic constants of the scaffold were then computed with Hooke's law for a linear-elastic isotropic material. The model was able to predict the small-strain elastic modulus measured in the experiments to within one standard deviation. Thus, by knowing the microstructure of the scaffold, its bulk properties can be predicted from the material properties of the constituents.

Bone Substitutes↗

Preparation and storage of "leukocyte-depleted single donor" platelet concentrate: a step forward in effective haemotherapy.

"Leukocyte-depleted" platelet concentrates (LD-SDPC) were prepared by cotton-wool and by polyester filtration of "leukocyte-poor" PC collected by the elutriation technique. The storage characteristics of LD-SDPC were comparable to those of the filtered pools of multiple donor platelet concentrates (LD-MDPC). However, LD-SDPC were less activated and less damaged than LD-MDPC over a 7-day storage period, as evidenced by beta-thromboglobin percent release and lactic dehydrogenase percent leakage in both products. LD-SDPC were prophylactically transfused to 12 thrombocytopenic patients; the mean bleeding time was shortened from 12 min 20 sec to 4 min 39 sec. Corrected count increment (CCI) was 22.8 at 1 hr and 14.1 at 24 hr compared to 15.5 and 10.0, respectively, with standard PCs.

Blood Component Transfusion↗

Comparison of the tissue response to absorbable self-reinforced polylactide screws and metallic screws in the fixation of cancellous bone osteotomies: an experimental study on the rabbit distal femur.

The availability of absorbable fracture-fixation devices for clinical use calls for better knowledge of the reaction of bone tissue to absorbable polyester implants as compared with similar metallic devices. To examine and compare the tissue response to biodegradable and metallic screws within cancellous bone, a transverse transcondylar osteotomy of the distal femur was fixed with absorbable self-reinforced polylevolactide screws in 35 rabbits and with stainless-steel screws in 35 rabbits. New bone formation and consolidation of the osteotomy were examined histologically, histomorphometrically, and microradiographically within standardized sample fields 1, 3, 6, 12, 24, 36, and 48 weeks postoperatively. The intact contralateral femur served as the control. A vigorous osteoconductive response to the polylevolactide screws was observed at 3 weeks postoperatively, and the osteoid surface fraction was significantly higher in all follow-ups than in the contralateral femora. In the femora with metallic screws, new bone formation was seen 3, 6, and 12 weeks postoperatively, but at 24, 36, and 48 weeks the osteoid surface fraction did not differ significantly from that of the intact control femora. The total bone area was significantly larger in the femora with self-reinforced polylevolactide screws than in the control bone 6-48 weeks postoperatively; in the femora with metallic screws, this was found only at 6 and 12 weeks. After 48 weeks, the femora fixed with metallic screws had statistically smaller total bone area than the intact control femora. Solid bone union was seen in 84% of the osteotomies in the self-reinforced polylevolactide group and in 76% of those in the metallic group after 3 weeks or more. No signs of degradation of the self-reinforced polyleuolactide implant and only a mild foreign-body reaction with no accumulations of inflammatory cells to either self-reinforced polylevolactide or metallic screws were observed during the follow-up period. Both types of screws seemed to induce an osteostimulatory response around their threads. This phenomenon was transient for metallic screws but lasted for at least 48 weeks for self-reinforced polylevolactide screws. The polylevolactide screw does not seem to cause osteopenia at the implantation site. The fixation properties of both self-reinforced polylevolactide screws and metallic screws appear to be sufficient for the fixation of small fragments of cancellous bone.

Animals↗

Novel biodegradable copolyesters containing blocks of poly(3-hydroxyoctanoate) and poly(epsilon-caprolactone): synthesis and characterization.

Novel biodegradable polyester block copolymers have been synthesized by using well-defined poly(3-hydroxyoctanoate) (PHO) oligomers having a hydroxyl end group and an ester end group with M(n) values of 800, 2,500, 5,300, 8,000, or 20,000 as an elastomeric soft segment and poly(epsilon-caprolactone) as a more crystalline segment. These PHO oligomers prepared by methanolysis were subjected to block copolymerization with epsilon-caprolactone. The chemical structure of the copolymers was confirmed by (1)H NMR and (13)C NMR spectroscopy. All the copolyesters are semi-crystalline and two T(g) were observed by differential scanning calorimetry when the molecular weight of the PHO block is about 20,000.

Animals↗

Controlled release of goserelin from microporous polyglycolide and polylactide.

Two microporous biodegradable polyesters, i.e., PGA and PDLLA, were obtained by solid-state polymerization reaction from the sodium salts of the corresponding alpha-hydroxycarboxylic acids after washing out the by-product sodium chloride. The polymers were shaped by cold uniaxial pressing, by hot uniaxial pressing, and by extrusion at elevated temperature. Due to the special microporosity of the polymers, the introduction of drugs is possible at moderate temperature. The release kinetics of the model drug Phe and of the anti-tumor drug goserelin (an LH-RH agonist) from compacted polymer samples were fast (approx. 2 d). The release kinetics of goserelin were corrected for the decomposition of the drug. External coatings with PDLLA or PLLA obtained by immersion in polymer solution strongly slowed down the release kinetics in the case of the PDLLA coating, giving an almost linear release during 100 d. A coating with PLLA was unsuitable to slow down the release kinetics.

Antineoplastic Agents, Hormonal↗

Biodegradable injectable in situ depot-forming drug delivery systems.

The scope of drug-delivery systems has expanded significantly in recent years providing new ways to deliver life saving therapeutics to patients. The development of new injectable drug-delivery systems has provided new vistas and opened up unexplored horizons in the field of science, particularly in controlled drug delivery since these systems possess unique advantages over traditional ones, which include ease of application, and localized and prolonged drug delivery. In the past few years, an increasing number of such systems has been reported in the literature for various biomedical applications, including drug delivery, cell encapsulation, and tissue repair. These are injectable fluids that can be introduced into the body in a minimally invasive manner prior to solidifying or gelling within the desired site. For this purpose both natural (chitosan, alginates) as well as synthetic polymers (PEGylated polyesters, ricinoleic acid-based polymers) have been utilized. These systems have been explored widely for the delivery of various therapeutic agents ranging for anti-neoplastic agents like paclitaxel to proteins and peptides such as insulin, almost covering every segment of the pharmaceutical field. This manuscript focuses on the recent advancements in the area of in situ forming biodegradable polymeric drug-delivery systems.

Antineoplastic Agents, Phytogenic↗

Environmental scanning electron microscopy of personal and household products.

The ability to forego sample preparation and to make observation directly in the environmental scanning electron microscope has benefited both household and personal product research at Unilever Research. Product efficacy on biological materials such as microcomedones was easily ascertained. Skin biopsies were examined in a moist state with no sample preparation. Effects of relative humidity on detergents were visually determined by recreating the necessary conditions in the microscope. Effects of cooling rates on the morphology of softener sheet actives that remained on polyester fabric were characterized via dynamic experimentation.

Acne Vulgaris↗

Physiology, regulation, and limits of the synthesis of poly(3HB).

The properties of poly(3-hydroxybutyrate) combined with the fact that it can be produced easily by numerous prokaryotes from renewable resources and even from potentially toxic waste products using well-known fermentation processes have generated keen interest in this biopolyester as a substitute for chemo-synthetic petroleum-derived polymers in many applications. However, the high price of poly(3HB) compared with the conventional synthetic materials currently in use has restricted its availability in a wide range of applications. If the economic viability of poly(3HB) production and its competitiveness are to be improved, more must be found out about the phenotypic optimization and the upper limits of bacterial systems as the factory of poly(3HB). In this chapter, two aspects of poly(3HB) are reviewed--poly(3HB) formation as a physiological response to external limitations and overcoming internal bottlenecks, and poly(3HB) as a commercially attractive polyester. From a physiological viewpoint, the ability to synthesize and degrade poly(3HB) is considered an investment in the future and provides organisms with a selective advantage. Poly(3HB) is presented as a strategic survival polymer, and it is shown that growth-associated synthesis is not as rare as reported. The influence of the efficiency and velocity of cell multiplication and product formation, of poly(3HB) content and of productivity on the overall yield, and finally on the economics of the whole process are discussed and evaluated from the technological or consumer's point of view. The specific production rate and poly(3HB) content appear to be more important than the yield coefficients.

Chemical Engineering↗

Capillary sprouts in ovaries of immature superstimulated golden hamsters: a SEM study of microcorrosion casts.

A new polyester resin of low viscosity was used to study the three-dimensional structure of capillary sprouts of mature follicles and of corpora lutea. Vascular microcorrosion casts were obtained from ovaries of immature golden hamsters between days 4 and 7 after stimulation with pregnant mares' serum gonadotrophin (PMSG). On days 4 and 5 after PMSG, a nodular appearance of the organ was due to mature follicles and corpora lutea. Capillary sprouts were seen as dead-ending structures originating from the thecal capillary network. The sprouts were either concentrated around (follicle type 1) or towards (follicle type 2) the center of the antrum. Increased vascular permeability resulted in resin leakage only in type 2. Intact corpora lutea were characterized by radially grown capillary sprouts. Regressing corpora lutea showed a marked reduction of the vascular bed as displayed by filling defects in casts on day 6 and 7 after PMSG. It is assumed that: 1. Dead-ending capillary structures, resin leakage, and filling defects are not always artifacts of the microcorrosion cast technique, but can express functional microcirculatory changes. 2. The concentric growth of thecal capillary sprouts may be related to the presence of an intact follicular basal membrane, and the radial growth of sprouts be taken as a sign of a digested basal membrane.

Animals↗

Intraosseous cellular response to biodegradable fracture fixation screws made of polyglycolide or polylactide.

As biodegradable pins and screws have increasingly been used in the internal fixation of fractures, sterile inflammatory reactions have occasionally occurred. The aim of the present experimental study was to assess the cellular response within cancellous bone to biodegradable polyester screws. In 45 rabbis a transverse distal femoral osteotomy was fixed with a 4.5 x 30 mm screw made either of polyglycolide (PGA, in 20 rabbits) or polylactide (PLA, in 25 rabbits). The follow-up times were 3, 6, 12, 36 or 48 weeks. The time-related and spatial characteristics of the cellular response were examined histomorphometrically using standardised sample fields under polarised-light microscopy. Polymorphonuclear granulocytes and mononuclear round cells were scarce in all follow-up groups. The occurrence of phagocytic cells (mononuclear macrophages and foreign-body giant cells) was highest in the PGA-fixed 12-week specimens. The giant cells seemed to adhere to the implant surface at an early stage, whereas the ultimate digestion and clearing of the decomposing polymeric material later on were performed by macrophages invading the implant body. No PGA was left in the 36-week specimens, while the gross geometry of the PLA screws was still intact at 48 weeks. In conclusion, the inflammatory response to these polymers was quite mild. Thus it seems probable that some other additional factors must influence the occurrence of the clinical inflammatory reactions.

Animals↗

An experimental study of tensile strength of six different suture techniques.

Tests were carried out on the strength of six different suture techniques used to join polyester lace ends, for example, in interscapulo-scapulocostal scapulopexy. The following sutures were used: four 5-cm rows of a continuous suture, four 2.5-cm rows of a continuous suture, two 5-cm rows of a continuous suture, 4 or 8 interrupted sutures, and 4 U-sutures. The laces were tested in tension, and load and elongation recorded. The strongest techniques involved a suture of four 5-cm rows of continuous thread (average maximum load at point of failure 1484 N). This was higher than the maximum load at failure of the point of attachment to the scapula.

Analysis of Variance↗