Tissue restoration after implantation of polyglycolide, polydioxanone, polylevolactide, and metallic pins in cortical bone: an experimental study in rabbits.

We performed qualitative and histoquantitative investigations of tissue restoration after implanting polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins in the intramedullary canal of rabbit femurs. The effect of bioabsorbable devices on healing of a cortical bone defect was also assessed. The cortical bone defect was created in the right femur of 80 rabbits. Bioabsorbable and metallic pins in 60 and two metallic pins alone were implanted in 20 intramedullary canals; 80 left femurs served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. At all time points, collagenous connective tissue, including bone trabeculae, surrounded the implant at the tissue-implant interface, replacing hematopoiesis and fat of the intramedullary canal. The groups did not differ in the area and trabecular bone area fraction of the resulting callus. Residual fragments of PGA and PDS were observed at 24 weeks, and complete degradation occurred within 52 weeks. PGA, PDS, PLLA, and metallic implants induced a bony and fibrous walling-off response in the intramedullary cavity. No inflammation was observed. Complete tissue restoration did not occur within the follow-up, even after complete degradation of PGA and PDS, which had shorter degradation times than PLLA. The cortical bone healing effect was not different between bioabsorbable pins and metallic wires. Thus, these polymers had no specific osteostimulatory or osteoinhibitory properties compared to stainless steel. Within the follow-up period, there were no significant differences in biocompatibility between the implants and no adverse inflammatory foreign-body reactions.

Tissue response to polyglycolide, polydioxanone, polylevolactide, and metallic pins in cancellous bone: An experimental study on rabbits.

The purpose of this study was to investigate, qualitatively and histoquantitatively, the tissue response of rabbit femur cancellous bone to polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins under identical conditions. Eighty knees in 50 rabbits were operated on by inserting bioabsorbable pins (PGA, PDS, or PLLA) together with metallic Kirschner wire in 60, and two metallic Kirschner wires alone in 20 knees, while 20 knees served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. Cancellous bone tissue response to implants was studied using histological, histomorphometrical, microradiographical, and oxytetracycline fluorescence methods. Residual fragments of PGA and PDS were seen at 24 weeks. Complete degradation of these polymers had taken place before 52 weeks. No signs of degradation of the PLLA pins were observed within the entire follow-up period. The osteoid formation surfaces at tissue implant-interface were statistically larger in all test groups as compared to intact controls. The number of macrophages at tissue implant-interfaces increased in all bioabsorbable implant specimens until 6 weeks, and with PGA until 12 weeks. No differences in the osseous response emerged when comparing groups of bioabsorbable implants with each other or with stainless steel group. Bioabsorbable pins and metallic Kirschner wires evoked an osteoconductive response in the cancellous bone surrounding implant, but the response intensity between implants displayed no differences. This suggests a simple, nonspecific walling-off new-bone front type of response. Consequently, the polymers possessed no specific osteostimulatory or osteoinhibitory properties. Within the follow-up, no significant differences in biocompatibility between the implants appeared, and no frank inflammatory foreign-body reactions occurred. The small-volume pins obviously did not exceed the local tissue tolerance and clearing capacity of the bone.

Long-term tissue response to bioabsorbable poly-L-lactide and metallic screws: an experimental study.

Late, clinically manifest, adverse inflammatory reactions have sometimes occurred after the use of slowly degrading bioabsorbable poly-l-lactide (PLLA) devices in clinical series of bone fixation. In this study, long-term tissue response to bioabsorbable fracture fixation screws made of poly-l-lactide and to similar metallic screws in cancellous bone was examined and compared with intact bone. The postoperative evaluation of the rabbit femora was performed by using plain radiography, microradiography, histology, histomorphometry, and oxytetracycline labeling studies. The follow-up times were 36 and 51 months in groups of 15 and 14 rabbits, respectively. A walling-off response by formation of trabecular bone which outlined the screw profile was observed in the PLLA and metallic groups both. Connective tissue between this bone front and the implant was seen only in the PLLA group. There was no difference in the thickness of the layer between the two follow-up groups. Between the surgically handled femora and the intact control bone, there was no statistically significant difference in the amount of trabecular bone. The osteoid formation activity in the tissue-implant interface showed no differences between the groups. However, active osteoblasts were visible only in the PLLA group. The amount of birefringent PLLA material diminished between the 36-month and the 51-month follow-up groups. Within the follow-up times of this study, both the PLLA screws and the metallic screws were rather inert. Also, long-term walling-off was a typical response to both PLLA and metallic screws in cancellous bone. PLLA screws did not evoke any osteostimulatory reaction over the long-term follow-up. The findings clearly demonstrated that the overall degradation process of PLLA was very slow and accompanied by fibrous tissue formation. Macrophage activity seemed to be related to the slow degradation process of PLLA and might be associated with the formation of connective tissue replacing the original implant. The results of this study showed no significant differences between the bioabsorbable PLLA screws and the metallic screws in biocompatibility, and no signs of inflammatory foreign-body reactions occurred during the follow-up.

Surgical decompression in dogs with thoracolumbar intervertebral disc disease and loss of deep pain perception: A retrospective study of 46 cases.

The case details and outcome after surgical decompression of 46 dogs with thoracolumbar intervertebral disc disease with loss of deep pain perception prior to surgery were reviewed. Nineteen dogs (41.3%) recovered with a median follow-up period of 12.5 months. Recovery was defined as an ambulatory paraparesis, or better, with urinary and fecal continence. There was a better outcome in dogs with loss of deep pain for less than 24 hours prior to surgery (19/41; 46.3% recovered) than in dogs without deep pain perception for more than 24 hours (0/5; 0% recovered). Dogs with deep pain perception present at two weeks postoperatively had significantly higher success rate (8/12; 66.7% recovered) than dogs without deep pain perception at this time period (1/10; 10.0% recovered). The return of deep pain perception by two weeks postoperatively can be a useful positive prognostic indicator.

Enzymic degradation of a beta-lactam antibiotic, ampicillin, in the gut: a novel treatment modality.

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.

Platelet-derived growth factor receptor inhibition reduces allograft arteriosclerosis of heart and aorta in cholesterol-fed rabbits.

BACKGROUND: Crosstalk between pro-inflammatory cytokines and platelet-derived growth factor (PDGF) regulates smooth-muscle-cell proliferation in cardiac-allograft arteriosclerosis. In this study, we tested the effect of STI 571, a novel orally active protein tyrosine kinase (PTK) inhibitor selective for PDGF receptor (PDGF-R) on transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. METHODS: Cardiac allografts were transplanted heterotopically from Dutch Belted to New Zealand White rabbits. A 0.5% cholesterol diet was begun 4 days before transplantation. Recipients received STI 571 5 mg/kg per day or vehicle intraperitoneally throughout the study period of 6 weeks. Cyclosporine A was given as background immunosuppression. RESULTS: In cardiac allografts of vehicle-treated rabbits, 76.2+/-2.1% of medium-sized arteries were affected by intimal thickening, and the percentage of arterial occlusion was 45.0+/-5.0%. Treatment with STI 571 reduced the incidence of affected medium-sized arteries to 41.2+/-8.1% (P <0.05) and the arterial occlusion to 27.6+/-5.0% ( P<0.05). In addition, we observed that STI 571 treatment reduced intimal lesion formation in proximal ascending aorta of transplanted hearts from 72.3+/-19.9 to 12.7+/-1.9 microm ( P<0.05). Our results also show that STI 571 significantly inhibited accelerated arteriosclerosis in medium-sized arteries of recipients' own hearts. CONCLUSIONS: The results of the present study suggest that PDGF-R activation may regulate the development of transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. Thus, PTK inhibitors may provide new strategies for prevention of these fibroproliferative vascular disorders.

The diagnostic value of contrast-enhanced magnetic resonance imaging in the detection of experimentally induced anular tears in sheep.

STUDY DESIGN: An investigation of the visualization of experimental anular tears using contrast-enhanced magnetic resonance imaging. OBJECTIVES: To investigate how different kinds of experimentally induced anular tears can be visualized on contrast-enhanced magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: Because the outer part of the anulus is innervated, tears of this part of disc are considered one cause for lumbar back pain. Moreover, clinical and experimental studies suggest that anular injuries may lead to a progressive degeneration of the entire disc. In the human disc, vascularized anular tears associated with disc degeneration can be visualized with contrast-enhanced magnetic resonance imaging, but acute peripheral anular injuries, probably caused by sudden trauma, have not been studied with this method. METHODS: Two adjacent lumbar discs in adult sheep (n = 11) were injured with a scalpel blade. The L2-L3 discs were injured superficially, whereas in the L3-L4 discs, the incision reached the nucleus pulposus (full-thickness injury). In seven animals, only a stab incision was made to the disc, and in four animals, a small fragment (5 x 2 x 3 mm) of anulus was cut and removed. The animals were killed 3 weeks (acute injury, n = 5) and 3 months (subacute injury, n = 6) after surgery. Five minutes before death, gadolinium-diethylenetriaminepentaacetic acid was injected intravenously. After death, the whole lumbar spines were excised and 1.5-T high-field magnetic resonance imaging was immediately performed. Thereafter, the disc samples were examined histologically to determine the existence of blood capillaries. RESULTS: In all injured discs, the injured area was macroscopically visible. Histologically, blood capillaries, lamellar destruction, and granulation tissue were clearly seen in every injured anulus. Contrast-enhanced magnetic resonance imaging showed that the superficial injuries were only occasionally visible in magnetic resonance imaging (3 of 11), whereas the full-thickness injuries were visible in a majority of the discs (8 of 11). In magnetic resonance imaging, the size of the injury did not relate to the enhancement intensity. The subacute injuries, particularly the full-thickness injuries, were more often visualized than the acute ones. CONCLUSION: Even though macroscopically visible and histologically evident, it was not always possible to demonstrate experimental anulus injuries by contrast-enhanced magnetic resonance imaging. This experimental study shows that further research work is needed to develop more sensitive methods to detect peripheral, relatively small, but probably clinically important disc injuries.

Healing of subcapital femoral osteotomies fixed with self-reinforced poly-L-lactide screws: an experimental long-term study in sheep.

Subcapital femoral osteotomies of ten young adult sheep were fixed with two bioabsorbable, self-reinforced, poly- L-lactide (SR-PLLA) lag screws of 4.5 mm in diameter. At 3 weeks radiographs were taken to check the reduction and fixation achieved. After follow-up periods of 12 weeks, 1 year and 3 years with three sheep in each group, and of 7 years and 4 months with one sheep, the sheep were killed, and the healing of the osteotomies, degradation and tissue response of the implants were examined radiographically, histologically and microradiographically. All osteotomies healed with a firm bony union. There was no dislocation or wound infection. Histologically, there was no marked tissue response in the bone tissue. At 12 weeks the implants were grossly intact, at 1 year granulation tissue and new bone formation had started to penetrate into the implant, and at 3 years the implant area was mostly replaced by connective tissue and new bone, but implant material was still seen as little islands surrounded by some lymphocytes. At 7 years and 4 months, the implant material had been degraded and replaced by tight bone. Self-reinforced poly- L-lactide lag screws seem to possess adequate mechanical properties and good biocompatibility for this demanding fixation.

Hereditary and clinical characteristics of lateral luxation of the superficial digital flexor tendon in Shetland sheepdogs.

A study was conducted to define the mode of inheritance of lateral luxation of the superficial digital flexor (SDF) tendon in different lines of Shetland sheepdogs by examination of pedigree data. This pedigree analysis included affected and unaffected dams, sires, and offspring; common clinical signs; and age at onset. The clinical, histopathologic, and radiographic features of the disease were also studied. Of the 14 offspring from five matings of an affected sire to unrelated affected females, 100% were affected with lateral luxation of the SDF tendon. Of the 59 offspring from the same affected sire to unrelated, unaffected females, 44% were affected. The mating between normal parents produced 61% unaffected and 39% affected offspring. Application of the phenotypic findings in this study to a Mendelian genetic model of inheritance suggests that lateral luxation of the superficial digital tendon in Shetland sheepdogs is inherited as a simple autosomal recessive trait.

Transmission electron microscopic visualization of the degradation and phagocytosis of a poly-L-lactide screw in cancellous bone: a long-term experimental study.

The increasing clinical use of biodegradable implants in orthopedic surgery makes it necessary to determine their long-term behavior in tissues. In this study, a biodegradable screw made of poly-L-lactide (PLLA) was inserted axially into the right distal femur in 18 rabbits. The degradation and phagocytosis process of PLLA was assessed histologically and by transmission electron microscopy (TEM). The follow-up times were 3 and 4.5 years for groups of nine and eight animals, respectively. Abundant birefringent polymeric material was still present in the center of the implant channel in all specimens in both follow-up groups. The PLLA material studied appeared to be a biologically relatively inert material, with only sparse reactive cellular activity at the tissue-implant boundary. In the TEM specimens, polymeric particles of an average area of 2 microm2 were seen to be located intracellularly within phagocytic cells. The spheric and polygonal particles were membrane-bound and to a great extent filled up each phagocyte. In the 4.5-year specimens, the size of the polymeric particles, measured as area and perimeter, was significantly smaller (p < 0.02) than that of the 3-year specimens. The findings indicate that the ultimate degradation process of PLLA is much longer than it previously was thought to be. Complete degradation probably still would have taken years after the 4.5-year span of this study.