Riitta-Mari Tulamo

Consolidation of craniotomy lines after resorbable polylactide and titanium plating : A comparative experimental study in sheep

&NA; The consolidation process of craniotomy lines in a skeletally immature large mammal was studied. A traditional narrow titanium miniplate was compared with a 0.5‐mm‐thick, 12‐mm‐wide absorbable punched self‐reinforced poly‐L‐lactide (SR‐PLLA) plate, both fixed with titanium miniscrews over bilateral parietal 2.5‐mm‐wide stable transosseous craniotomies on nine female sheep (16 to 20 months old). After 6, 12, 20, 52, and 104 weeks, cross‐sectional histology, histomorphometry, and oxytetracycline chloride fluorescence studies were done to compare the healing process of the craniotomy lines and to study the biocompatibility and the degradation process of the SR‐PLLA plate. The consolidation pattern supported the principle of guided tissue regeneration: under the wide, resorbable plate osseous bridging proceeded evenly throughout the line, whereas titanium plating led to bulky, uneven growth in the bone margins. All SR‐PLLA‐plated osteotomy lines had healed completely by 20 weeks, whereas none of the titanium‐plated lines had consolidated during a follow‐up of 1 year. The nonossified gaps were filled with dense connective tissue. Histomorphometric analysis showed that osseous bridging proceeded significantly faster on the resorbable plate side compared with the titanium side (p < 0.001). The osteoid surface fraction over the total trabecular surface was highest at 6 weeks, being 63 percent on the SR‐PLLA side and only 36 percent on the titanium side. The oxytetracycline chloride fluorescence studies confirmed these findings. After 52 weeks, there was no osteoid or oxytetracycline chloride fluorescence left as a sign of terminated ossification, even in the nonconsolidated titanium sides. Microscopic cracking of the plate was evident at 12 to 20 weeks, and the first signs of active resorption were present at 52 weeks. After 2 years, the plate had disappeared and tiny polylactide particles were being actively resorbed. The biocompatibility of SR‐PLLA and titanium was good, and no adverse cellular reactions to these materials were noted, except a clinical foreign body reaction caused by loosened titanium miniscrews. A densely punched, 0.5‐mm‐thick self‐reinforced PLLA plate seems to retain its integrity for a sufficiently long time to complete osseous healing of a 2.5‐mm‐wide craniotomy line in the sheep calvarial area. A thin, wide fixation plate enables superior healing, especially in osseous defects. The degradation process of the SR‐PLLA plate begins within 1 year and is far advanced after 2 years. By using absorbable SR‐PLLA fixation plates instead of metallic plates, a subsequent operation for the removal of the implants can be avoided. SR‐PLLA devices could thus be a potential additive or even alternative to metallic implants in craniofacial surgery. (Plast. Reconstr. Surg. 101: 123, 1998.)

Material properties of a

A study was carried out to investigate changes in mechanical properties and degradation of self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) rods in vitro and in vivo. The viscosity-average molecular weight, Mv, of the intact sterile (gamma irradiated) rods was around 50 000 g mol-1. The SR-PLA96 rods of diameter 1.1 mm by 30 mm and diameter 4.5 mm by 50 mm were immersed in phosphate-buffered saline or implanted in the dorsal subcutis of rabbits. Bending, shear and torsion strength and bending modulus, together with the changes of viscosity and crystallinity, were measured up to 24 wk. The strength values showed only a slight decrease during the follow-up period with the exception of torsion strength, that decreased to 52% of the initial value during 24 wk. There were no statistically significant differences in the strength retention between in vitro and in vivo groups. Crystallinity increased over time, being 46–49% at 24 wk. The Mv of the rods decreased over 50% by 24 wk. These promising results motivated us to continue the studies with the fixation of experimental cortical bone osteotomies with SR-PLA96 intramedullary rods.

Pathology of Natural Cases of Equine Endocrinopathic Laminitis Associated With Hyperinsulinemia

Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were described in 14 laminitic horses and ponies that had hyperinsulinemia (>20 mIU/l), with reference to 25 age- and breed-matched controls. The type and severity of lesions noted had no correlation with reported clinical duration and in at least some cases must have preceded it. Lesions were largely localized abaxially within the lamellar tissue and included apoptotic cell death, as well as lamellar fusion, hyperplasia, and partial replacement with aberrant keratin containing nucleated debris and proteinaceous lakes. The lesions resulted in irregular margins between the inner horn and the lamellar tissue. Acute separation originated from the abaxial region, with minimal associated inflammation. Axially, epidermal lamellar tapering was the most frequent morphological observation. The lesions in these chronic cases of laminitis were similar to those described in some inflammatory laminitis models and contained features seen in developmental phases of hyperinsulinemic models. These findings support the theory that repeated episodes of subclinical laminitis occur prior to clinical presentation. In addition, the pathology does not include extensive basement membrane failure seen in some inflammatory models.

Evaluating Complementary Therapies for Canine Osteoarthritis Part I: Green-lipped Mussel (Perna canaliculus)

A green-lipped mussel (GLM) preparation was evaluated in a randomized, double-controlled and double-blinded clinical trial. It was hypothesized that the treatment effect would be less than that of the positive control (carprofen) but more than that of the negative control (placebo). Forty-five dogs with chronic pain and a radiographic diagnosis of osteoarthritis that were randomly allocated into one of three groups completed the study. All dogs were fed the test products or placebo for 8 weeks. The dogs were evaluated four times, at 4-week intervals. Six different variables were assessed: veterinary-assessed mobility index, two force plate variables, owner-evaluated chronic pain index and pain as well as locomotion visual analogue scales (VASs). Intake of extra carprofen was also evaluated. A chi-squared and a Mann–Whitney test were used to determine significance between groups. When changed to dichotomous variables, there were more dogs in the GLM than in the placebo group that improved, according to veterinary-assessed mobility, owner-evaluated chronic pain index and pain VAS (P = 0.031, P = 0.025, P = 0.011, respectively). For the same three, the odds ratio and their confidence interval were over one. The extent of improvement was significantly different between the GLM and the control in veterinary-assessed mobility (P = 0.012) and pain VAS (P = 0.004). In conclusion, GLM alleviated chronic orthopedic pain in dogs although it was not as effective as carprofen. As no side-effects were detected, GLM may be beneficial in dogs e.g. when non-steroidal anti-inflammatory drugs cannot be used.

Intramedullary fixation of cortical bone osteotomies with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) rods in rabbits.

Osteotomies of the femoral diaphysis were fixed with absorbable self-reinforced fibrillated poly-96L/4D-lactide (SR-PLA96) intramedullary rods (4.5 mm x 50-60 mm) in 43 adult rabbits. Follow-up times varied from 3 weeks to 3 yr. After sacrifice histological, oxytetracycline-fluorescence and microradiographic studies of the bones were performed. Strength characteristics and changes in crystallinity and molecular weight of the rods were also measured. All osteotomies were evaluated radiographically. Thirty-six osteotomies (84%) healed uneventfully. The implant disappeared almost totally within 3 yr and histology showed only a minor foreign body reaction. From 6 weeks on, the bending force needed to break the osteotomy was comparable to the bending force needed to break the control bone. The shear strength of the rods displayed only minor changes for the first 24 weeks. Subsequently, the rods rapidly lost their strength and at 48 weeks there was practically no shear strength left, which is ideal for healing of an osteotomy. The present investigation demonstrated, that absorbable. fibrillated SR-PLA96-rods can be used for the intramedullar fixation of simple cortical bone osteotomies in rabbits. These results have encouraged us to continue our studies with the fixation of experimental cortical bone osteotomies in larger species.

Biodegradable and titanium plating in experimental craniotomies: a radiographic follow-up study.

Plain film radiography and computed tomography (CT) were evaluated in assessing the consolidation of experimental craniotomy lines covered with titanium miniplates or biodegradable self-reinforced poly-L-lactide (SR-PLLA) plates. Two sagittal (2.3–2.5 mm wide and 22 mm long) symmetrical craniotomy lines were made in the skulls of eight young sheep. One craniotomy line was covered with a biodegradable SR-PLLA plate and the other with a titanium miniplate. Both plates were fixed with four titanium miniscrews. Consolidation of the osteotomies was studied using plain film radiography and CT 6,12, 20, and 52 weeks postoperatively. Microradiography and histology were used for reference. Plain film was not reliable in assessing osseous consolidation because false-positive results were obtained in three osteotomies. Osseous consolidation was more reliably assessed by CT, which showed consolidation on the SR-PLLA side within 20 weeks, whereas none of the titanium-plated lines was consolidated by 52 weeks. Superior consolidation under the resorbable plate was confirmed in histology and microradiography. The radiolucent SR-PLLA plates did not interfere with CT, whereas the titanium plates caused minor CT artifacts.

Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate

Objective: To study the short and long term effects of radiosynovectomy on articular cartilage in growing and mature rabbits. Methods: The articular cartilage of the distal femurs of rabbits was examined four days, two months, and one year after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate ([166Ho]FHMA). Arthritic changes were evaluated from histological sections by conventional and polarised light microscopy, and glycosaminoglycan measurements using safranin O staining, digital densitometry, and uronic acid determination. Proteoglycan synthesis was studied by metabolic [35]sulphate labelling followed by autoradiography, and electrophoretic analysis of extracted proteoglycans. Northern analyses were performed to determine the mRNA levels of type II collagen, aggrecan, and Sox9 in cartilage samples. Results: Radiosynovectomy had no major effect on the histological appearance of articular cartilage in mature rabbits, whereas more fibrillation was seen in [166Ho]FHMA radiosynovectomised knee joints of growing rabbits two months after treatment, but not after one year. Radiosynovectomy did not cause changes in the glycosaminoglycan content of cartilage or in the synthesis or chemical structure of proteoglycans. No radiosynovectomy related changes were seen in the mRNA levels of type II collagen, whereas a transient down regulation of aggrecan and Sox9 mRNA levels was seen in young rabbits two months after [166Ho]FHMA radiosynovectomy. Conclusions: [166Ho]FHMA radiosynovectomy caused no obvious chondrocyte damage or osteoarthritic changes in mature rabbits, but in growing rabbits some transient radiation induced effects were seen—for example, mild cartilage fibrillation and down regulation of cartilage-specific genes.

Intraosseous plating: a new method for biodegradable osteofixation in craniofacial surgery.

Biodegradable miniplates and screws offer special possibilities for surgical techniques because the removal operation is avoided. In areas beneath thin skin, intraosseous plating could be preferable to avoid palpability and transient swelling during resorption. The tissue reaction to a 0.5-mm-thick self-reinforced poly-L-lactide (SR-PLLA) plate fixed with an SR-PLLA miniscrew was studied histologically and histomorphometrically after implantation into the calvarium of six young sheep. After follow-up periods of 6, 20, and 52 weeks, no signs of adverse tissue reaction such as clinically manifest foreign body reaction or histologically manifest osteolysis were noted. By 52 weeks the implants were largely in direct contact with remodeled, dense bone tissue. No signs of fragmentation or resorption were noted in the intraosseous parts of the implants, whereas the screw head had been fragmented and was undergoing resorption at 52 weeks. The screw head is unnecessary in this plating method and could have been removed with a hot wire loop. The excellent biocompatibility of the mechanically strong, resorbable SR-PLLA plate with miniscrew fixation provides a possibility for intraosseous plating in less loaded craniofacial areas, especially in areas with very thin soft-tissue coverage.

Long-term bone tissue reaction to polyethylene oxide/polybutylene terephthalate copolymer (Polyactive®) in metacarpophalangeal joint reconstruction

The poly-L/D-lactide 96/4 joint scaffolds are used to engineer fibrous tissue joints in situ for the reconstruction of metacarpophalangeal joints. In this experimental study, a supplementary elastomeric stem made of Polyactive 1000PEO70PBT30 (a segmented block copolymer of polyethylene oxide and polybutylene terephtalate with 70/30 PEO/PBT ratio) was used to anchor the joint scaffold in the arthroplasty space. Eleven resected fifth metacarpophalangeal joints of minipig were reconstructed and evaluated radiologically and histologically for 3 years. Plain joint scaffold and Swanson silicone implant arthroplasties (11 of each) in metacarpophalangeal joints of minipig served as controls. Altogether fore limbs of eighteen minipigs were operated for the study. Deleterious tissue reaction with dramatic signs of osteolysis and inflammatory foreign-body reaction was observed around the Polyactive stems. The mean maximum diameter of the osteolytic stem cavity was statistically wider when compared to the mean maximum diameter of Swanson implant group during the first postoperative year. Numerous osteoclasts were found at the margins of the osteolytic areas. No direct bone contact could be seen. At 1 year osteoblastic regeneration and formation of new trabecular bone followed. Finally the foreign-body reaction settled, but the adjoining bones were at this stage highly sclerotic and composed of coarse trabeculae. In contrary to previous in vivo studies suggesting biocompatibility, osteoconductivity and capability to bond to bone, Polyactive 1000PEO70PBT30 stem in this setting caused massive osteolytic lesions and foreign-body reactions.

Evaluating Complementary Therapies for Canine Osteoarthritis—Part II: A Homeopathic Combination Preparation (Zeel®)

A homeopathic combination preparation (HCP) for canine osteoarthritic pain was evaluated in a randomized, double-controlled and double-blinded clinical trial. Forty-four dogs with osteoarthritis (OA) that were randomly allocated into one of three groups completed the study. All dogs were fed test products or placebo for 8 weeks. The dogs were evaluated at the clinic four times, with 4-week intervals. Six different variables were assessed: veterinary-assessed mobility, two force plate variables, an owner-evaluated chronic pain index and pain and locomotion visual analogue scales (VASs). Intake of extra non-steroidal anti-inflammatory drugs was also evaluated. A Chi-squared test and a Mann–Whitney test were used to determine significant improvement between groups. When changed into dichotomous responses of ‘improved’ or ‘not improved’ three out of the six variables showed a significant difference (P = 0.016, P = 0.008, P = 0.039) in improved dogs per group, between the HCP group and the placebo group. The odds ratios were over one for the same variables. As extent of improvement in the variables from start to end of treatment, the HCP product was significantly more improved in four (P = 0.015, P = 0.028, P = 0.049, P = 0.020) of the six variables, compared with the placebo. Our results indicated that the HCP Zeel® was beneficial in alleviating chronic orthopedic pain in dogs although it was not as effective as carprofen.