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At least 19 recordsLinked to original sources

PubMed2005

Histologic and mechanical evaluation of impaction grafting for femoral component revision in a goat model.

A goat model of revision hip arthroplasty was used to examine the histology and mechanical performance of impaction grafting using two femoral stems varying in stem surface finish. There were no significant mechanical or qualitative histologic differences between smooth, tapered, polished stems and step-cut, grit-blasted stems. Allograft distribution, bone incorporation, and cement mantle thickness were not uniform within the femoral canal. Efforts to improve the impaction grafting technique may be more important than stem design.

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PubMed1997

In vivo forces during remodeling of a two-segment anterior cruciate ligament graft in a goat model.

An existing goat model was used to measure in vivo graft forces during walking, to determine if the forces set at surgery change over time under the same external load and if the forces in the graft during in vivo function can be dictated by the forces set at surgery. The anterior cruciate ligament was reconstructed in 12 goats with use of a composite graft consisting of a bone-patellar tendon-bone autograft and a synthetic augmentation segment. The forces in the graft segments were established intraoperatively by a force-setting technique. In five animals, the tendon segment was set to carry 90% of the total graft force, and in the seven other animals, the augmentation segment was set to carry 90% of the total force. The total graft force was the same in all animals. Graft forces due to anterior tibial loads of 67 N were measured before and after fixation and 6 weeks after surgery with the use of buckle transducers mounted extra-articularly over the anterior tibia. They were also measured during straight, level walking at 6 weeks. The forces changed significantly from just after surgery to 6 weeks later, such that the initially set load-sharing was eliminated by 6 weeks. At 6 weeks, a relatively smooth gait had been achieved, and the maximum total graft force in each animal during walking averaged 35 N and was of similar magnitude to forces generated by the anterior tibial loads of 67 N with the animal anesthetized. After fixation, forces in the tendon graft segments were significantly different between the group with high set forces and that with low set forces. At 6 weeks, when functional joint loads were approaching normal levels, the graft segment forces for the two groups were not significantly different. Load-sharing between tendon and augmentation segment and load in the tendon segment at 6 weeks could not be dictated at surgery.

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PubMed2006

Evaluation of novel Brucella melitensis unmarked deletion mutants for safety and efficacy in the goat model of brucellosis.

Pregnant goats were employed to assess unmarked deletion mutant vaccine candidates BMDeltaasp24, BMDeltacydBA, and BMDeltavirB2, as the target host species naturally infected with Brucella melitensis. Goats were assessed for the degree of pathology associated with the vaccine strains as well as the protective immunity afforded by each strain against abortion and infection after challenge with wild-type Brucella melitensis 16M. Both BMDeltaasp24 and BMDeltavirB2 were considered safe vaccine candidates in the pregnant goat model because they did not cause abortion or colonize fetal tissues. BMDeltaasp24 was isolated from the maternal tissues only, indicating a slower rate of clearance of the vaccine strain than for BMDeltavirB2, which was not isolated from any maternal or fetal tissues. Both strains were protective against abortion and against infection in the majority of pregnant goats, although BMDeltaasp24 was more efficacious than BMDeltavirB2 against challenge infection.

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PubMed2006

Primary spinal segment stability with a stand-alone cage: in vitro evaluation of a successful goat model.

BACKGROUND: Interbody cages have been developed to restore disk height and to increase stability of the spinal segment, and thereby enhance fusion. However, they often prove inadequate as a stand-alone device. It is unknown how much primary stability is required to facilitate fusion. In various goat studies, we have obtained spinal fusion routinely with a stand-alone cage device. However, data covering the mechanical conditions under which these fusions have been obtained are lacking. In this study, we addressed the issue of primary stability. METHODS: We used an established goat model for spinal fusion in vitro. 48 native lumbar spine segments were mechanically tested in flexion/extension, axial torsion (left/right), anterior/posterior shear, and left/right lateral bending. Then all segments were provided with a titanium cage using the exact surgical procedure of our earlier in vivo studies, and the mechanical tests were repeated. Under shear force and axial torsion, a significant loss of stiffness was seen in the operated segments as compared to nonoperated controls. No increase in stiffness was found in any of the loading directions. INTERPRETATION: Cage implantation in a lumbar spinal segment does not increase immediate postoperative stability as compared to the native segment in this goat model. This is attributable to both the annular damage during cage implantation and the subsequent loss of segment height. Yet previous in vivo studies using this goat model have generally shown fusion. This implies that high primary segment stability is not required for fusion or, alternatively, that the tested range of motion of the spinal segment in vitro does not occur at these magnitudes in vivo.

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PubMed2003

A biomechanical and histological evaluation of the structure and function of the healing medial collateral ligament in a goat model.

This study evaluated the healing process of an isolated medial collateral ligament (MCL) rupture at 12 weeks in a goat model. Using a robotic/UFS testing system, knee kinematics in multiple degrees of freedom and in situ forces in the healing MCL in response to (1) a 67-N anterior tibial load and (2) a 5-Nm valgus moment were evaluated as a function of angles of knee flexion. Then a uniaxial tensile test of femur-MCL-tibia complexes (FMTCs) was preformed to obtain the structural properties of the FMTC and mechanical properties of the healing MCL substance. The histological appearance of the healing MCL was also examined for collagen and cell organization. The anterior tibial translation in response to a 67-N anterior tibial load was found to range from 1.9 to 2.4 mm, which was not significantly different from the sham-operated, contralateral control knee. In response to a 5-Nm valgus moment, however, MCL injury caused a 40% or more increase in valgus rotations over sham-operated controls for all angles of knee flexion tested. The magnitudes of the in situ forces in the healing MCLs for neither external loading conditions differed from sham-operated controls. For the structural properties of the healing FMTC, the stiffness returned to sham-operated control levels, but ultimate load at failure remained 60% of sham-operated control values. In terms of mechanical properties of the healing MCL, its tangent modulus and stress at failure were only 40% of sham-operated control values. Histologically, the collagen and cell organization at the femoral and tibial insertions as well as the midsubstance remained disorganized. Comparing these data to those previously reported at 6 weeks, there was a marked improvement in the in situ forces in the healing MCL and of the stiffness of the FMTC. Also, the data obtained for the goat model revealed a faster healing process than those for the rabbit model. These findings suggest that greater post-injury activity levels may render the goat to be a better animal model for studying the healing process of the MCL.

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PubMed2007

Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device.

The purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) with a carboxymethylcellulose-stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly-L-lactic acid (PLLA) interbody cage packed with either rhOP-1 and its carrier or autologous bone graft. The carrier material was bovine collagen type-1 stabilized with carboxymethylcellulose. The fusion segments were retrieved at 3 or 6 months postimplantation and evaluated by radiographic and histologic analyses. The rhOP-1 graft substitute, used in combination with the resorbable PLLA cage, showed inferior results as compared to autologous bone graft in the goat lumbar fusion model. Whereas four out of five segments from the autograft group were fused after 6 months, none of the four segments receiving the rhOP-1 graft substitute were fused at this time point. Bone ingrowth into the cage was delayed or absent in the experimental group, whereas all autograft specimens showed advanced bone ingrowth (3 months) or fusion (6 months). We suggest that the fusion process was inhibited, because cells were unable to penetrate the rhOP-1 graft material. This led to delayed bone formation and in some cases inadequate tissue formation.

Absorbable Implants↗

PubMed2026

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

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PubMed1999

Evaluation of cervical laminectomy and laminoplasty. A longitudinal study in the goat model.

STUDY DESIGN: An evaluation of the longitudinal radiologic changes up to 6 months induced by multilevel laminectomy and laminoplasty and the biomechanical responses in the goat model, complemented by biomechanical studies of intact specimens. OBJECTIVES: To determine the long-term radiographic differences and biomechanical responses of laminectomy and laminoplasty in an in vivo animal model. SUMMARY OF BACKGROUND DATA: Previous clinical and laboratory studies have indicated that multilevel laminectomy can cause increased flexibility in the cervical spinal column. Although the potential for laminoplasty to resolve these changes has been suggested, other evaluations have not supported this contention. Clarification of this controversy with long-term in vivo studies has not been performed. METHODS: Ten adult goats were divided into two groups, one undergoing C3-C5 laminectomy and the other open-door laminoplasty. Lateral cervical spine radiographs were obtained at 4-week intervals for a 6-month period. After the goats were killed, biomechanical testing was performed using pure moment loading on the surgically treated specimens and on three intact (without surgery) cervical spinal columns. RESULTS: In the laminectomy preparations, the cervical curvature index was noted to decrease by 59% at 16 weeks (P < 0.028) and by 70% at 24 weeks (P < 0.002), whereas the decrease in laminoplasty was not significantly different. Biomechanical testing indicated a significantly increased sagittal-plane slack motion in the laminectomy group (55 degrees) compared with that in intact specimens (39 degrees), but no significant difference between the laminoplasty and intact groups with respect to this motion. Laminectomy was found to be significantly stiffer (36%) in flexion than in extension, whereas the contrary was true for laminoplasty (37%). CONCLUSIONS: Radiographic and biomechanical results in the goat model suggest that laminoplasty is superior to laminectomy in maintaining cervical alignment and preventing postoperative spinal deformities.

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PubMed2005

Biopharmaceutics of intrathecal baclofen-loaded microparticles in a goat model.

The goal of this study was to develop a goat model allowing reliable pharmacokinetic (PK) studies of intrathecal baclofen (ITB) sustained release dosage forms using an implanted silicone catheter. ITB PK parameters (clearance, volume of distribution) following intrathecal bolus injection were determined for doses ranging from 100 to 560 microg and a comparison to human data was made. Baclofen-loaded microparticles were then implanted in the intrathecal space of goats and the resulting baclofen levels were determined during 28 days. Finally, PK parameters were used to predict cerebrospinal fluid (CSF) baclofen rates from in vitro release profiles of baclofen-loaded microspheres. The catheter was well tolerated and did not interfere with behavioral testings. Baclofen CSF clearance (mean = 8.59+/-2.43 ml/h) and volume of distribution (21.06+/-13.32 ml) were not significantly affected by the increase of the dose (p > 0.05). In vivo, the baclofen levels in CSF were stabilized at 200 microg/l after a period of 3 days. The predictive value of the in vitro release studies was good since the theoretical levels ranged between 128 and 257 microg/l. In conclusion, a large animal model was developed and allowed the biopharmaceutic evaluation of baclofen microparticles injected via intrathecal route.

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PubMed2006

Application of polylactides in spinal cages: studies in a goat model.

Spinal cages are currently made of non-resorbable materials, but they only have a temporary function: after fusion, resorption is desirable both from a biological and mechanical point of view. We studied different polylactides in stand-alone condition in a goat model. Cages were made of 100% poly(L-lactic acid) (PLLA) or 70/30 poly(L/DL-Lactic acid) (PLDLLA); titanium served as control. After six months, all titanium cages showed non-unions comparable to that observed in a clinical retrieval, thus showing validity of the goat model. PLLA cages maintained their mechanical integrity for six months, enough to allow fusion. After that, the material resorbed within 48 months without adverse tissue reactions. Bone formation was faster in PLDLLA cages, but these already failed within three months, thus losing their stabilising function: 50% ended in pseudo-arthrosis. Additional internal fixation provided enough stability for fusion (83%). Biocompatibility of both PLLA and PLDLLA was excellent. The long-term results show that PLLA cages can be used for stand-alone interbody fusion, and that PLLA is an improvement over titanium in terms of fusion rate. PLDLLA showed enhanced bone formation, but also earlier failure of the implant. Chances for spinal fusion were better with additional internal fixation.

Absorbable Implants↗

PubMed2003

Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation.

Autologous chondrocyte implantation (ACI) is an established technique to repair joint surface defects. Although there is some indirect evidence that the expanded chondrocytes are required to achieve proper healing, the role they play in the repair process is not clear yet. To monitor the persistence and the phenotype of the injected chondrocytes in the repair tissue (RT) we have optimized a fluorescent labeling protocol for articular chondrocytes, which allows cell tracking in vivo for up to 14 weeks, using the fluorescent dye PKH26. We have combined in vivo cell tracking, with the immune-detection of collagen type II protein in a goat model of ACI. Our data indicate that the implanted cells can persist for at least 14 weeks in the defects, can participate in the integration with the surrounding tissues, and become structural part of the RT, rich in collagen type II and sulfated proteoglycans. Albeit with a small number of samples, our data provide proof of principal that the implanted chondrocytes can contribute to structural cartilage repair in a goat model of ACI.

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PubMed2004

"All-inside" meniscal repair devices: an experimental study in the goat model.

BACKGROUND: Although the use of "all-inside" absorbable meniscal repair devices has become popular, numerous complications have been reported. The authors applied their well-established goat model to evaluate three "all-inside" meniscal repair devices. METHODS: A "tear" was created in the medial meniscus of both knees in 26 goats. The animals were randomized into four groups, and the meniscus was treated as follows: (A) meniscal repair with Mitek Fastner, (B) meniscal repair with BioStinger, (C) meniscal repair with Mitek Clearfix Screw, and (D) no repair. All animals were sacrificed at 6 months postoperatively, and all specimens were carefully evaluated and results recorded and compared with historical results of meniscal repair with suture in this same animal model. RESULTS: Meniscal repair results with all three all-inside devices studied were inferior to suture repair. Chondral injury was present in 75% to 100% of repairs with all-inside devices and none of the control specimens. DISCUSSION: / CONCLUSION: Although new all-inside meniscal repair devices are relatively quick and easy, results may not be as good as with traditional suture techniques. The high rate of chondral injury associated with these devices in the goat model is worrisome for chondral damage in humans, especially in patients with smaller or tighter knees.

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PubMedDate not supplied

Biologic remodeling after anterior cruciate ligament reconstruction using a collagen matrix derived from demineralized bone. An experimental study in the goat model.

A matrix of demineralized cortical bone was used to reconstruct the anterior cruciate ligament in the goat model. This graft underwent considerable site-specific remodeling and transformation from a Haversian system at time zero into a ligament-like structure at 1 year. This transformation included new bone formation filling the osseous tunnels and replacing the demineralized matrix, development of a ligament-like transition zone within the graft, and ligamentous collagen orientation with crimp in the intraarticular portion of the graft. One year after surgery, the mean anterior-posterior translation in the reconstructed stifle joints at 30 N of tibial loading was 2.1 +/- 0.4 (+/- SEM). The mean ultimate force to failure for the reconstructed ligament at 1 year was 474 +/- 146 N compared with the time-zero (initial) strength of the matrix of 73 +/- 9 N. The cellular repopulation of the graft had no associated inflammatory cells. The potential clinical significance of these findings includes 1) replacement of a collagen matrix with bone within the osseous tunnels, 2) establishment of a more physiologic fibrocartilage transition at the graft insertion site, 3) the time-zero structural properties of a collagen matrix increasing to more desired values with biologic remodeling, and 4) a sterile biologic allograft with essentially no long-term inflammatory response.

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PubMed2004

An evaluation of the quasi-linear viscoelastic properties of the healing medial collateral ligament in a goat model.

The viscoelastic properties of the healing medial collateral ligament (MCL) at 12 weeks after isolated injury were investigated in a goat model. The stress-strain relationships, static and cyclic stress-relaxation behaviors of the healing MCL up to 5% strain were determined experimentally using a femur-MCL-tibia complex. These experimental data were used in combination with the quasi-linear viscoelastic (QLV) theory of Fung (1972) to characterize the reduced relaxation function, G(t) (described by constants C, tau1, and tau2) and the elastic response, sigmae(epsilon) (described by constants A and B) of this tissue. It was found that the percentage of stress relaxation for the healing MCLs was significantly greater than those for sham-operated controls (49.0 +/- 12.1% vs. 26.5 +/- 8.1%, respectively; p < 0.05). The product of constants A x B, i.e. the initial slope of the stress-strain curves, was found to be significantly lower for healing MCLs compared to those for sham-operated controls (32.9 +/- 15.8 MPa vs. 118.8 +/- 48.3 MPa; p < 0.05). The dimensionless constant C, i.e. the magnitude of the viscous response, was nearly three times greater for healing MCLs, while constant tau1 was found to be similar between the two groups (0.80 +/- 0.43 s vs. 0.89 +/- 0.52 s, respectively). Constant tau2 for the healing MCL was significantly less than the controls (1269 +/- 38 s vs. 1845 +/- 431 s; p < 0.05) indicating that the stress relaxation reached a plateau earlier. These constants of the QLV theory used to describe the healing MCL were validated for the strain level utilized in this experiment (approximately equal to 4.5%) by predicting the peak stresses during a cyclic stress-relaxation experiment. The theoretically determined values closely matched the experimentally measured values. Thus, this study demonstrates that the QLV theory could be successfully used to describe the viscoelastic behavior of the MCL during the early phases of healing.

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PubMed2004

Follow-up of osteochondral plug transfers in a goat model: a 6-month study.

BACKGROUND: Osteochondral transfer procedures are increasingly used to resurface full-thickness articular cartilage defects. There has not been long-term assessment/description of autogenous donor and recipient sites. HYPOTHESIS: The healing process occurs at the donor/host cartilage and bone interfaces. STUDY DESIGN: Histologic, biochemical, and biomechanical changes were assessed 6 months after an osteochondral transfer in a goat model. METHODS: Eight adult goats were studied. In the 6 osteochondral transfer goats, 2 autogenous plugs were transferred from the femoral trochlea to defects in the weightbearing portion of the medial femoral condyle. The goats were allowed free range for 6 months. Randomly assigned plugs were assessed. RESULTS: Knees of the sacrificed animals had preservation of the joint space with mild chondromalacic changes in both transfer and contralateral control groups. Histologically, no evidence of cartilage (host/donor) healing was seen. Subchondral bone of the plug was contiguous with the surrounding recipient bone. Cellular viability in the autogenous osteochondral plug was seen, and 35SO4 uptake of the articular cartilage was not statistically different from the contralateral control condyle. The indentation stiffness of the transfer plug (mosaicplasty) and the contralateral donor site were similar--much stiffer than normal cartilage including surrounding condylar cartilage. Large structural stiffness of transferred cores and donor sites appeared to be related to their thinner cartilage layer. CONCLUSIONS: At 6-month follow-up, a cleft between host and transferred articular regions remained, with no integration between the two. CLINICAL RELEVANCE: Autogenous transplantation of osteochondral plugs is possible with integration of subchondral bone and preservation of chondral viability.

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PubMed2002

Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: part 1.

BACKGROUND: The acute effects of cardiomyoplasty in an experimental model of chronic dilated heart have not been thoroughly investigated. Therefore, a model of chronic left ventricular (LV) dilatation was created to accurately determine actual changes shortly after passive and active wrapped skeletal muscle. METHODS: A carotid-jugular shunt model in 8 goats was used to induce progressive dilatation of the cardiac ventricles. Geometric modifications induced by the arteriovenous shunt were monitored by transthoracic echocardiography. After 8 weeks, cardiomyoplasty was performed, and the acute hemodynamic changes obtained with static cardiomyoplasty soon after the wrapping procedure were determined. Hence, hemodynamic variables recorded during assisted cardiac beats were then compared with data collected with unassisted cardiac beats using the conductance catheter method to generate pressure-volume loops. RESULTS: During electrical stimulation of the unconditioned skeletal muscle wrapped around the dilated left ventricle, a significant increase in stroke volume (117 +/- 48 mL versus 87 +/- 38 mL; p < 0.05) was observed. Early wrapped latissimus dorsi muscle activation also induced a reduction in LV end-systolic volume (from 51 +/- 28 mL to 27 +/- 14 mL; p < 0.05) when compared with unassisted LV contraction. CONCLUSIONS: In a chronic model of cardiac dilatation, acute dynamic cardiomyoplasty was shown to increase LV contractile performance and reduce LV volume. Further evaluation is necessary to show the effects of a conditioned wrapped muscle on LV systolic function and dimensions in the long-term.

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PubMed2000

Interaction between the ACL graft and MCL in a combined ACL+MCL knee injury using a goat model.

The optimal treatment for the MCL in the combined ACL and MCL-injured knee is still controversial. Therefore, we designed this study to examine the mechanical interaction between the ACL graft and the MCL in a goat model using a robotic/universal force-moment sensor testing system. The kinematics of intact, ACL-deficient, ACL-reconstructed, and ACL-reconstructed/ MCL-deficient knees, as well as the in situ forces in the ACL, ACL graft, and MCL were determined in response to two external loading conditions: 1) anterior tibial load of 67 N and 2) valgus moment of 5 N-m. With an anterior tibial load, anterior tibial translation in the ACL-deficient knee significantly increased from 2.0 and 2.2 mm to 15.7 and 18.1 mm at 30 degrees and 60 degrees of knee flexion, respectively. The in situ forces in the MCL also increased from 8 to 27 N at 60 degrees of knee flexion. ACL reconstruction reduced the anterior tibial translation to within 2 mm of the intact knee and significantly reduced the in situ force in the MCL to 17 N. However, in response to a valgus moment, the in situ forces in the ACL graft increased significantly by 34 N after transecting the MCL. These findings show that ACL deficiency can increase the in situ forces in the MCL while ACL reconstruction can reduce the in situ forces in the MCL in response to an anterior tibial load. On the other hand, the ACL graft is subjected to significantly higher in situ forces with MCL deficiency during an applied valgus moment. Therefore, the ACL-reconstructed knee with a combined ACL and MCL injury should be protected from high valgus moments during early healing to avoid excessive loading on the graft.

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PubMed2002

Resorbable cages for spinal fusion: an experimental goat model.

A biomechanical cadaver study and an in vivo monosegmental spinal fusion study were performed to evaluate a novel bioresorbable poly-L-lactic acid (PLLA) cage. The yield strength of a spinal segment was chosen as the main design parameter for the resorbable cages to be used in a goat model. A 3-year in vivo study revealed a significantly faster and more complete fusion using PLLA cages as compared to titanium cages with the same dimensions. In the PLLA group, the intervertebral grafting height did not change and bone remodeling within the cage was completed 2 years after implantation. In terms of degradation of the PLLA, similar features were observed in vivo and in vitro. Degradation was almost completed 3 years after implantation. Tissue reaction was mild during the 3-year period.

Absorbable Implants↗