Timo Nevalainen

Drug-eluting biodegradable poly-D/L-lactic acid vascular stents: an experimental pilot study.

Purpose: To evaluate in vivo a new drug-eluting biodegradable vascular stent with respect to biocompatibility, neointimal hyperplasia formation, and reliability. Methods: Self-expanding biodegradable poly-96L/4D-lactic acid (PLA) stents with 2 drugs (PLA + dexamethasone [DEX] and PLA + simvastatin [SIM]) and 2 different coatings (PLA + P(D,L)LA and PLA + polycaprolactone [PCL]) were compared with a self-expanding stainless steel Wallstent. The stents were implanted in both common iliac arteries of 8 pigs. Prior to sacrifice at 1 month, angiography was performed to determine patency. Specimens were harvested for quantitative histomorphometry; vascular injury and inflammation scores were assigned to the stented iliac segments. Results: All stented arteries were angiographically patent. The mean luminal diameter (3.05 mm) and area (30.36 mm2) of DEX-eluting PLA stents were decreased compared to other stents (PLA + P(D,L)LA: 3.66 mm and 43.92 mm2 PLA + SIM: 4.21 mm and 56.48 mm2 PLA + PCL: 4.19 mm and 54.64 mm2 Wallstent: 5.01 mm and 81.19 mm2). Wallstents and DEX-eluting PLA stents induced minimal intimal hyperplasia: PLA + DEX: 0.16 mm, PLA + P(D,L)LA: 0.35 mm, PLA + SIM: 0.33 mm, PLA + PCL: 0.29 mm, and Wallstent: 0.18 mm. The vascular injury scores demonstrated only mild vascular trauma for all stents. Only mild to moderate inflammatory reaction was noted around stent struts with a vascular inflammation score. Conclusions: Biodegradable polymer stents appear to be biocompatible and reliable, causing minimal neointimal hyperplasia. Furthermore, the new biodegradable poly-D/L-lactic acid stent can be used as a local drug delivery vehicle. The DEX-eluting PLA stent reduces neointimal hyperplasia. The findings show a need for further investigation to prove the efficacy and safety of this new biodegradable drug-eluting stent.

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.

Histology of injected autologous fascia in the paralyzed canine vocal fold

Objective To evaluate the histology of minced and injected autologous fascia graft in the augmentation of unilateral vocal fold paralysis.

Implementing the 3Rs in Neuroscience Research: A Reasoned Approach

The 3Rs--replacement, reduction, and refinement--are aimed at minimizing the welfare costs to animals used in research. Some neuroscientists fear that implementing the 3Rs will prohibit essential studies. Others view them as fundamental ethical principles that improve the quality of research. A regulatory system that integrates science and welfare is most likely to deliver public confidence.

Fixation of distal femoral osteotomy with an intramedullary rod: Early failure of carbon fibre composite implant in rabbits

A novel composite material with an ultra-high strength and a low elastic modulus, comprising a carbon fibre reinforced liquid crystalline polymer (LCP/CF) has been developed. An experimental osteotomy of the distal femur in nineteen rabbits weighing on average 4.8 (3.7-6.3) kg was fixed with an intramedullary LCP/CF rod of 3.2 mm in diameter and 50 mm in length. The initial mechanical properties of the rods had a mean shear strength of 180 MPa, a flexural strength of 450 MPa, and a flexural modulus of 40 GPa. The rods were implanted for periods of 3, 6, 12, 24, and 52 weeks. The healing of the osteotomy was analyzed by radiographic, histological, microradiographic, and oxytetracycline fluorescence studies. The strength retention of the LCP/CF rods was measured by mechanical testing. Solid union of the osteotomy was seen within 6 weeks. The implants retained their original strength properties up to 52 weeks. In three rabbits, a non-union with granulation tissue and carbon fibre particles was noticed at the osteotomy site, where disruption of the implant surface was seen at the level of the osteotomy. Further studies with a special interest in the fabrication process of the LCP/CF-implants are needed.

Comparison of ear tattoo, ear notching and microtattoo in rats undergoing cardiovascular telemetry

Individual and permanent identification of experimental animals is a common and often essential research practice. There is little information available on the short-term effects of these procedures on the animals. In this study, seven rats were implanted with telemetric devices. The effects of three different identification methods (ear tattoo, ear notching and microtattoo) were compared. Cardiovascular data were collected for 24 h after the procedures. Time periods of 0–1, 1–4, 4–16 h (dark) and 16–24 h after the procedure were analysed separately. The most pronounced differences in measured parameters were observed during the first hour after the procedures were performed. Mean arterial pressure (MAP) was significantly higher (P < 0.012) following the ear tattoo than the microtattoo procedure by a difference of approximately 5 mmHg. Heart rate (HR) was significantly elevated (P < 0.001) after ear tattoo compared with both ear notching (Δ = 31 beats per minute [bpm]) and microtattoo (Δ = 44 bpm). During the 1–4 h period and the following dark period, the MAP was highest in the ear notching group, but no differences were observed in the HRs. During the following dark period (4–16 h) and the next day (16–24 h) differences in MAP and HR were minor. In conclusion, microtattoo appears to cause the mildest changes in HR and blood pressure. Based on these results, ear tattoo and ear notching should be replaced by microtattoo whenever possible.

Fixation of femoral shaft osteotomy with an intramedullary composite rod: An experimental study on dogs with a two-year follow-up

A novel composite material with an ultra-high strength and a low elastic modulus called carbon fibre-reinforced liquid crystalline polymer (LCP/CF) has been developed. An experimental diaphyseal osteotomy of the proximal femur in fourteen Beagle dogs was fixed with an intramedullary LCP/CF rod of 4.5 mm in diameter and 80 mm in length. The radiological follow-up intervals were 1, 3, 6, 12, 24, 52, and 104 weeks. Five dogs were killed at 1 year and three dogs at 2 years for histological studies; six dogs were retained for longer follow-up. Radiographs showed an uncomplicated healing of the diaphyseal osteotomy with an external callus formation in all dogs in 12 weeks. Histological analysis revealed a benign host tissue response with few inflammatory cells. Both bone and fibrous tissue were seen at the LCP/CF-host tissue interface. The cross-sectional cortical area of the operated femur was slightly greater than that of the control femur in the 2-year follow-up. LCP/CF showed promising properties for high-load applications.

The effect of an intramedullary carbon-fiber-reinforced liquid crystalline polymer implant on bone : An experimental study on rabbits

A novel composite material with an ultra-high strength and a low elastic modulus called carbon-fiber-reinforced liquid crystalline polymer (LCP/CF) has been developed. We studied the effects of an intramedullary LCP/CF rod on bone in rabbits. A LCP/CF rod of 3.2 mm in diameter and 50 mm in length was introduced into the intramedullary canal of the right femur in ten rabbits weighing an average of 3.6 (3.1-4.2) kg. The follow-up intervals were 3 and 52 weeks. No signs of deformity or osteopenia were seen in the operated femurs in the radiographic, histological, and histomorphometric studies. Histologically, the implant was enclosed by cancellous bone in the metaphyseal area and by a thin cancellous bone cuff in medullary cavity. Bone was able to grow in direct contact with the LCP/CF rod. No signs of degradation of the implants or of adverse tissue reaction were seen. The intramedullary LCP/CF rod had no harmful effects on bone in rabbits. The biocompatibility of the LCP/CF appeared to be good. This novel composite material demonstrates properties that may be useful in orthopedic applications.

Food and water intake, growth, and adiposity of Sprague-Dawley rats with diet board for 24 months

Ad libitum (AL) feeding of rats leads to obesity and increased result variability, as well as premature morbidity and mortality. It may also alter metabolism and responses to foreign compounds. Moderate dietary restriction (DR) reduces these untoward effects without compromising the sensitivity of rodent bioassays. The diet board (DB) is a novel method for achieving moderate DR in group housing. Food pellets are firmly attached into grooves in an aspen board, and rats have to gnaw the wood in order to eat. Food is available continuously, but due to the effort involved rats eat less. This study simulated a chronic safety test to assess the long-term effects of DB feeding. A total of 146 male and female outbred Sprague-Dawley rats, nine weeks old at onset, were housed in groups of three and fed either AL or with DBs for two years. Food and water consumption were measured at six time points. The rats were weighed every one to two weeks. Body and tibial lengths and epididymal fat weight were measured at necropsy. Modified body mass index was calculated at five time points after one year of age. DB feeding reduced body weight and fat tissue moderately, more so in males. DB males ate less than AL males, but no differences were seen in the total food consumption in the females. There was no consistent difference in the within-group variations of the measured parameters. DB is a workable DR method, albeit some modification could enhance and standardize its DR effects, especially in female rats.

Refining cage change routines: comparison of cardiovascular responses to three different ways of cage change in rats

Cage change is one of the unavoidable routines in laboratory rodent care. However, cage change disrupts the rodents’ olfactory environment and can evoke stress reactions. In this study, the short-term cardiovascular responses to three different cage change procedures were compared with telemetric monitoring. These procedures were: placing the rats into a new, clean cage (NEW), transferring the old cage lid into the clean cage (LID) and transferring an enrichment object into the clean cage (ENR) with the animals. Seven outbred rats (four Hsd:Sprague-Dawley and three HsdBrlHan:WIST) were instrumented with telemetric transmitters. The reactions were recorded during the 24 h following the cage change procedures. All cage change procedures (and also simple handling) caused elevated heart rate and mean arterial pressure levels for up to 5 h after the procedure, with the largest effect seen during the first hour. The reactions observed after cage change were significantly (P < 0.05) greater than those observed after simple handling. The reactions after NEW were significantly higher than the reactions after ENR or LID, though the results were dependent on the stock. In Wistar rats the LID procedure resulted in smaller reactions than ENR. In Sprague-Dawley rats, the differences between ENR and LID were not so clear, but the transfer of scent-marked material into the new cage decreased the reactions compared with the NEW procedure also in this stock. Based on these results, using the old cage lid on the new cage could reduce the disturbance of cage change in rats.