The bisphosphonate ibandronate accelerates osseointegration of hydroxyapatite-coated cementless implants in an animal model

Background There is evidence that bisphosphonates can improve fixation of cementless metal implants by enhancing the extent of osseointegration. The current preclinical study examined whether the nitrogen-containing bisphosphonate ibandronate can accelerate this process, resulting in early achievement of secondary stability and sealing of the bone–implant interface to prevent wear debris migration. Methods The study was conducted on 88 female Sprague-Dawley rats in which uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the medullary canal of each femur. The animals were randomly assigned to receive subcutaneous treatment with 1.0, 2.5, or 5.0 μg/kg per day ibandronate or saline solution as a control. The extent of osseointegration expressed by the osseointegrated implant surface was quantified by histomorphometry at eleven time points during the study period. To determine the time course of osseointegration, the data were expressed using third-order polynomial regression analysis. Results For hydroxyapatite-coated implants, the highest dose of ibandronate (5 μg) reduced the time for a sufficient implant fixation of 60% osseointegrated implant surface to 18 days compared to 38 days in the control group. This reduction of 20 days (52.6%) represents a halving in the time required for sufficient osseointegration of the implant. For hydroxyapatite-coated implants and low-dose ibandronate application (1 μg, 2.5 μg) and for uncoated titanium implants, acceleration of osseointegration was not observed in any of the study arms. Conclusion Continuous treatment with 5 μg/kg per day ibandronate is potent in accelerating osseointegration of hydroxyapatite-coated implants. As a result, improved early secondary stability and prevention of wear debris migration by the sealing of the implant–bone interface can be expected, therefore prolonging the long-term survival of the implant.     

Migration of polyethylene particles around stable implants in an animal model

The aim of this study was to test the hypothesis that a tight seal between bone and implant will eliminate the avenue of particle migration around stable implants. Three types of implants were used in rabbits (polished press-fit Ti-6Al-4V or plasma-sprayed hydroxyapatite [HA]-coated Ti-6Al-4V) or doughy stage polymethyl methacrylate (PMMA). Implants were placed in the condylar notch. Each animal received an intra-articular injection of high density polyethylene (PE) particles (10(8) in 0.4 mL; mean size 4.7 microns) at 4 and 6 weeks postoperatively. Eight weeks postoperatively, peri-implant tissues were examined for PE particles and osteolysis. In all cases, intracellular PE particles were seen at the bone-implant interface and within marrow. No osteolysis was observed. Bone apposition was determined by computerized image analysis. There was no significant difference in the percentage of bone apposition (+/- SD) among the three groups of implants: Ti-6Al-4V (68% +/- 19%), HA-coated Ti-6Al-4V (70% +/- 10%), and PMMA (59% +/- 12%). These results indicate that a polished Ti-6Al-4V surface is as effective as PMMA or HA coating in limiting migration of PE particles around stable osseointegrated implants in rabbits.     

Goats as an osteopenic animal model.

A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.     

Antigenicity of polyester (Dacron) vascular prostheses in an animal model.

Objectives to investigate the specific humoral immune response to three different polyester (Dacron) prostheses in pigs. Design, materials and methods twenty-four growing pigs were randomly divided into three groups. The infrarenal aorta was replaced by a segment of collagen-impregnated woven polyester prosthesis (low, medium and high porosity). Serum antibodies were detected by modified enzyme immunoassay using non-impregnated prosthesis as the target for the blood samples taken on experimental days 1, 10, 17, 24, 62 and 116 of the 22 pigs followed over the whole observation period. Results significantly enhanced (p <0.05) mean IgG antibody binding against polyester was detected on experimental days 10, 17, 24 and 62 with antibody prevalences of 41%, 41%, 32% and 37%, respectively. Antibody positive pigs were divided into early responders (n =9) and late responders ( n =5) with antibody detection on day 10 and/or 17 vs day 62 and/or 116. No significant differences between the three different prostheses were found. The formation of specific IgG antibodies against polyester in the animals investigated demonstrates a broad individual variability. Conclusions polyester is an antigenic polymer. Specific antibodies, reflecting the inflammatory response, might be not only a parameter for testing biomaterials but also for determining individual bio(in)compatibility for long-term biomaterial function.     

Development of an animal model for assessment of the hemostatic efficacy of fibrin sealant in vascular surgery

PURPOSE: Sustained hemostatic function of fibrin sealant (FS) is crucial when it is used in cardiovascular surgery. The purpose of this study was to develop a model that can determine the long-term hemostatic efficacy of tissue sealants in a vascular surgery. METHODS: To determine the ability of the model to detect differences in FS performance, various concentrations of FS were prepared and tested. Tensile strength of FS clots was determined in vitro using a tensiometer. Laparotomy was performed on 49 anesthetized rabbits, and a segment of the aorta was occluded, transected, and then sutured in an end-to-end fashion with four or eight interrupted 9-O sutures. The four-suture repair was covered with FS or placebo, and blood flow restored. Spilled blood was absorbed with gauze and weighed to estimate blood loss. Four weeks after surgery the animals were euthanized and the vessels recovered for histology. RESULTS: Average tensile strength of FS clots at 120, 90, and 60 mg/ml topical fibrinogen complex (TFC) concentration was 0.42 +/- 0.07 N, with no significant difference among them. The lowest TFC concentration, 30 mg/ml, produced weaker clots than either 120 or 90 mg/ml (P < 0.05). All rabbits with four-suture anastomoses that were treated with placebo bled to death after the vessel was unclamped (n = 6). Treatment of suture line with standard FS concentration (120 mg/ml TFC, n = 8) sealed the anastomosis and prevented blood loss. Hemostasis was sustained for 4 weeks, allowing vascular healing. All rabbits with the eight-suture anastomosis survived the operation but lost 42 +/- 9.2 ml blood (n = 5). Hemostatic efficacy of FS was unchanged when TFC was diluted to 90 mg/ml (n = 6) but further dilution to 60 mg/ml with water (n = 8) produced significantly less effective clots, with an average blood loss of 5.5 +/- 7.6 ml (P < 0.05) and two fatal clot failures postoperatively. When FS was diluted to 60 mg/ml TFC with a buffer, it maintained its hemostatic strength (n = 6). Further TFC dilution to 30 mg/ml led to consistent bleeding with an average blood loss of 35.3 +/- 10.3 ml (P < 0.001, n = 6). CONCLUSIONS: The four-suture anastomosis of rabbit aorta offers a consistent and reliable method for evaluating the short- and long-term hemostatic efficacy of FS products. This model is not only able to determine the functional differences in various concentrations of FS, but it is also sensitive to detect the subtle changes in FS preparation (e.g., medium composition) that is not detected by in vitro testing.     

Tissue expander capsule as an induced vascular bed to prefabricate an axial vascularized buccal mucosa-lined flap for tubularized posterior urethral reconstruction: preliminary results in an animal model

Surgical repair of complex posterior urethral disruptions remains one of the most challenging problems in urology.The efficacy of using a tissue expander capsul...     

建立更加稳定和有效的兔耳瘢痕模型

目的：建立更加稳定和有效的兔耳瘢痕模型。方法：选用16只新西兰大耳白兔,分别在兔耳腹侧中段作1cm×1cm的全层皮肤缺损共192个,以形态学、瘢痕增生指数及羟脯氨酸（HPr）的含量变化对创面愈合后形成的增生块,进行动态组织病理学、细胞增殖活性及胶原纤维合成等检测。结果：兔耳腹侧中段创面可产生类似于人类的增生性瘢痕,其发生率为91．5％,增生块最长持续时间可达120多天。结论：采用本实验的模型复制方法,可以得到更加稳定和有效的兔耳增生性瘢痕。     

建立一种兔耳增生性瘢痕的动物模型

目的　建立由动物自身产生的与人增生性瘢痕类似的增生性动物模型。方法　选用2 4只新西兰大耳白兔 ,分别在兔耳腹侧、背侧面作直径 1.5cm的全层皮肤缺损各 14 4个、72个 ,对创面愈合后形成的增生块进行组织病理学、层黏连蛋白 (LN)mRNA及整合素 β1mRNA检测等检查。结果　兔耳腹侧创面可产生类似人增生性瘢痕样的过度增生 ,其发生率为 71% ,以兔耳腹侧面中部为著 ,增生块最长持续时间超过伤口愈合后 15 0d ,而兔耳背侧面的创面增生块发生率不到3 0 % ,且增生块持续时间短 ,为 76d。切片镜下显示 ,增生块的真皮层存在大量成纤维细胞 ,与人增生性瘢痕结构类似。结论　兔耳腹侧面尤其腹侧面的中部可产生类似人增生性瘢痕样病理改变 ,可望成为研究瘢痕的动物模型。     

Extra-projected implants as an alternative surgical model for breast reconstruction. Implantation strategy and early results

The present study reports on patients who underwent breast reconstructions with extra-projection implants. Two-hundred and thirty-four women were treated for 238 breast reconstructions irrespectively of breast shape and size. In this series we aimed to reconstruct for all women a bilateral cosmetic medium-size breast (between 400 and 500cc), highly projected, with a little to moderate ptosis rather then a ptotic one exactly matching the contra-lateral. This is demonstrated by volume of implants that ranged from 397cc for ladies with small breast who received an augmentation, to 533cc for those who side required a reduction surgery. Eighty-six percent of patients received contra-lateral procedures. Complication rate was 8.4% and 66% of reconstructions were rated as good in the patients' opinion. Extra-projection implants, coupled with contra-lateral breast surgery, provide a good aesthetic outcome and avoid myocutaneous flaps only on the basis of breast size and shape.     

The avascular talus: revascularization in an animal model

Avascular necrosis of bone such as the talus can lead to collapse and loss of function. To avoid this, early revascularization has been proposed as an important event. Revascularization can occur either by vessel growth directly through the bony surface, or by vessel growth into the periosteum or ligaments with secondary reconnection to the bone. The ability to attract new vessels (angiogenesis) of the bony surface and the connective tissue was compared in an animal model. A talus isograft (all cortical surface, periosteum, and ligaments remaining; n = 11) or a sector of a femoral head isograft (cancellous surface, no connective tissue; n = 12) of adult mice was implanted into dorsal skinfold chambers of mice of the same strain. The implants were observed by intravital microscopy every 12 hours. First indicators of angiogenesis were hemorrhages around the implants (tali: 11 of 11, 72 +/- 12 hours; femoral heads: 6 of 12, 84 +/- 24 hours). Next, a sudden redness of the transplant indicated marrow hemorrhage (tali: 9 of 11 after 84 +/- 36 hours; femoral heads: 10 of 12 after 96 +/- 36 hours). Histology showed clear growth of capillaries into the cancellous surface of the femoral heads and possible growth of capillaries into the ligament stumps (tali). However, there was widespread necrosis of the marrow cells indicating failure of recirculation. A cancellous bony surface as well as the soft tissues attached to the bone provided a stimulus to rapid revascularization of the grafts. This model was able to evaluate differing rates of early partial revascularization for various bone surfaces, which may have implications for studying treatment options for certain fracture dislocations (e.g., in the talus).     

Dual effect of nitrate therapy for cyclosporine-induced hypertension on vascular and platelet morphofunctional markers; an animal model

The present study sought to evaluate the prevention and reversion effects of isosorbide-5-mononitrate (Is-5-Mn) on the development of hypertension (HT) and on the underlying vascular and platelet morphofunctional disturbances, using an animal model of cyclosporine (CsA)-induced HT. The following rat groups (n = 8) were tested: (1) a control group (orange juice, for 7 weeks); (2) the CsA group (5 mg/kg/d for 7 weeks); (3) the Is-5-Mn group (150 mg/kg/d, twice a day for 7 weeks); (4) the prevention group (Is-5-Mn + CsA) treated for 2 weeks with Is-5-Mn only and thereafter with both drugs for 7 weeks; (5) the curative group (CsA + Is-5-Mn) beginning 7 weeks after CsA and following thereafter with both drugs for 5 weeks. Blood pressure, lipid profile, vascular lesion, platelet aggregation and morphology, and platelet thromboxane A(2)/vascular prostacyclin equilibrium were evaluated. Is-5-Mn + CsA therapy prevented (systolic blood pressure [SBP]: 114.3 +/- 1.9 mm Hg, P < .001; diastolic blood pressure [DBP]: 97.0 +/- 3.3 mm Hg, P < .001) the CsA-induced HT (SBP: 146.2 +/- 4.5 mm Hg, P < .001; DBP: 124.9 +/- 4.5 mm Hg, P < .001 vs control: SBP: 111.6 +/- 0.7 mm Hg; DBP: 94.6 +/- 1.0 mm Hg), as well as the vascular lesion and the platelet morphofunctional disturbances. The curative group did not show attenuated CsA-induced BP increase; it showed further enhancement of the HT effect (SBP: 159.7 +/- 5.5 mm Hg, P < .05; DBP: 132.8 +/- 2.8 mm Hg), as well as worsened vascular lesions and platelet function, namely a disruption in the TXA(2)/PGI(2) equilibrium. Our data suggested that Is-5-Mn therapy may be a valid choice to prevent the morphofunctional changes associated with CsA-induced HT, when used as a preventive therapy. A careful evaluation of the impact of nitrate therapy should be considered, particularly the negative effect on cardiovascular hemodynamics, when considering its use after previous CsA disturbances have been established.     

Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model.

An animal model was developed to study the pathophysiology of erectile dysfunction due to atherosclerotic vascular disease. Thirty one New Zealand white male rabbits were divided into control (n = 5) and treatment groups (n = 26). The control group was placed on a regular diet while the treatment group underwent balloon de-endothelialization of the aorto-iliac arteries and received 1.6% cholesterol and 4% triglyceride diet for eight weeks. After eight weeks in the control animals (n = 5), blood levels of cholesterol, triglycerides and low density lipoproteins, radiologic studies as well as hemodynamic parameters of erectile function were all normal. In the surviving treatment animals (n = 21) after the same time period, a significant increase in blood levels of cholesterol, triglyceride and low density lipoprotein were observed. In addition, 62% of these animals developed hypertension which was not observed in the control group. Angiographically, 10 animals (48%) demonstrated severe atherosclerotic lesions (75% to 100% occlusion of common or internal iliac arteries on one side and over 50% occlusion of the opposite side), five (24%) had moderate lesions (50 to 75% luminal occlusion of right and left common iliac or internal iliac arteries) and 6 revealed minimal lesions (less than 50% occlusion of the right and left common iliac or internal iliac arteries). Of the 15 animals with 50% or greater luminal occlusion of the iliohypogastric arteries, erectile dysfunction was found in 93% of cases. Due to the development of erectile dysfunction in 33% of animals with minimal occlusive lesions, it appears that factors, other than large vessel luminal occlusion, may exist in this animal model which adversely influence erectile function. This model may therefore be of further benefit in the study of other factors associated with atherosclerosis and impotence, such as the possible concomitant hypercholesterolemic and atherosclerotic-induced alterations in the local reactivity of corpus cavernosum smooth muscle and lacunar space endothelial cells.     

Skin toxicity of sodium lauryl sulfate as evidenced in an animal model

This study presents the toxic effects of a very known and used compound in pharmaceutical products and from cosmetic market, a detergent (surface-active) anionic. The presented data underlined the effects of an ointment base with sodium lauryl sulfate, with various concentrations of this detergent, respectively: 0.5%, 1% and 3%, in a long term utilization of this, on an animal model with Sprague Dawley rats.     

Tongue replantation in an animal model

Although the tongue is not a vital organ in sustaining life, it may be a vital organ in sustaining the will to live in many people. As carcinoma of the tongue represents the majority of the 30,000 oral cavity cancers diagnosed per year in the United States, many patients face the potential consequences of resection of part or all of the tongue for cure. To date, reconstructive options do not restore optimal tongue function including articulation, swallowing, taste, or sensation. With the ultimate goal of improving tongue reconstruction, we report on a successfully performed autograft transplantation of the tongue in an animal model. Before undertaking allograft transplantation of the tongue, an autograft tongue transplant would be attempted to identify the feasibility of such a procedure and to determine the similarity of an animal model with human techniques. The dog's neck, tongue, and oral anatomy represent an excellent animal model for tongue reconstruction. This procedure can be performed successfully in an animal model. The only previously published replantation of the tongue involved the reattachment of the anterior portion of a human tongue after physical trauma. To our knowledge, the enclosed report represents the first successful total excision and replantation of the tongue in either a human or animal model.     

The incisor absent rat: an animal model for the study of otosclerosis

The incisor absent (ia) rat is introduced as an animal model for the study of otosclerosis. Previous animal models have failed to accurately reflect the dynamic nature of this disease. Auditory brainstem response testing suggested a conductive hearing loss in the incisor absent rat as compared to age-matched normal controls. The hearing loss, which was manifested during puberty, was progressive in nature up to 18 weeks of age. Microscopic dissection of the middle ear revealed bony abnormalities of the ossicles and oval window in the incisor absent rat. Scanning electron microscopy of the ossicles demonstrated bony lesions at the incudostapedial joint and stapes footplate. Histologic examination demonstrated thickened spongiotic bone involving the otic capsule and ossicles. The incisor absent rat model possesses an inheritable defect of the otic capsule and ossicles that results in a progressive conductive hearing loss. The genetically transmitted lesion appears histologically similar to otospongiosis. The bony pathology in the incisor absent rat is caused by defective osteoclasts and transplantation of bone marrow cells from normal rats to the incisor absent rats corrects the cellular abnormality. The incisor absent rat may represent the best animal model to date for the study of otosclerosis, its cause, and clinical treatment.     

The development of an animal model of glioma for use in experimental neuro-oncology

A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro in vivo model of human glioma. This paper describes the growth characteristics of tumours produced after intracerebral or subcutaneous inoculation of 497-P(1) cells into syngeneic VM mice. The results show that cell line 497-P(1) provides the basis for a reproducible animal model of glioma which fulfils many of the criteria required for experimental therapy studies.