Biomechanical properties of Achilles tendon repair augmented with a bioadhesive-coated scaffold.

The Achilles tendon is the most frequently ruptured tendon. Both acute and chronic (neglected) tendon ruptures can dramatically affect a patient's quality of life, and require a prolonged period of recovery before return to pre-injury activity levels. This paper describes the use of an adhesive-coated biologic scaffold to augment primary suture repair of transected Achilles tendons. The adhesive portion consisted of a synthetic mimic of mussel adhesive proteins that can adhere to various surfaces in a wet environment, including biologic tissues. When combined with biologic scaffolds such as bovine pericardium or porcine dermal tissues, these adhesive constructs demonstrated lap shear adhesive strengths significantly greater than that of fibrin glue, while reaching up to 60% of the strength of a cyanoacrylate-based adhesive. These adhesive constructs were wrapped around transected cadaveric porcine Achilles tendons repaired with a combination of parallel and three-loop suture patterns. Tensile mechanical testing of the augmented repairs exhibited significantly higher stiffness (22-34%), failure load (24-44%), and energy to failure (27-63%) when compared to control tendons with suture repair alone. Potential clinical implications of this novel adhesive biomaterial are discussed.

rhBMP-2 modulation of gene expression in infected segmental bone defects.

The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which received either bovine collagen carrier with 200 mug rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls at weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time.

Osteogenic protein-1 overcomes inhibition of fracture healing in the diabetic rat: a pilot study.

Type I diabetes mellitus inhibits fracture healing and leads to an increase in complications. As a pilot study, we used a closed fracture model in the diabetic rat to address the question of whether osteogenic protein-1 (OP-1) in a collagen carrier can overcome this inhibition by increasing the area of the newly mineralized callus and femoral torque to failure compared with diabetic animals with fractures treated without OP-1. Diabetes was created in 54 rats by injection of streptozotocin. After 2 weeks, a closed femur fracture was created using a drop-weight impaction device. Each fracture site was immediately opened and treated with or without 25 microg OP-1 in a collagen carrier. Animals were euthanized after 2 or 4 weeks. Fracture healing was assessed by callus area from high-resolution radiographs, callus strength from torsional failure testing, and undecalcified histologic analysis. The area of newly mineralized callus was greater in diabetic animals treated with 25 microg OP-1/carrier compared with diabetic animals with untreated fractures and with fractures treated with carrier alone. This increase in callus area did not translate into an equivalent increase in torque to failure. Osteogenic protein-1 showed some evidence of overcoming the inhibition of fracture healing in the diabetic rat.

Union of a chronically infected internally stabilized segmental defect in the rat femur after debridement and application of rhBMP-2 and systemic antibiotic.

OBJECTIVES: The goal of this study was to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would induce new bone formation in an internally stabilized segmental defect with a chronic bacterial infection in the rat femur and whether treatment with systemic antibiotic would enhance this effect. METHODS: A 6-mm unilateral femoral segmental defect was surgically created in 120 Sprague-Dawley rats, internally stabilized with a polyacetyl plate and 6 Kirschner wires, and contaminated with 10(4) colony-forming units of Staphylococcus aureus. After 2 weeks, all defects were surgically debrided and implanted with 0, 20, or 200 microg of rhBMP-2 in a type 1 bovine collagen sponge. Half of the animals in each treatment group received 4 weeks of systemic antibiotic, and half did not. Animals were euthanized at 4 or 12 weeks after debridement. Bone formation within and adjacent to the defect was assessed using microcomputed tomography, torsional failure testing and undecalcified histology. RESULTS: No substantial callus formed in the infected defects without rhBMP-2. Significantly more mineralized callus was induced with the higher dose of rhBMP-2 than with the lower dose (P = 0.001), with systemic antibiotic therapy than without (P < 0.001), and at 12 weeks after debridement compared with 4 weeks (P < 0.001). CONCLUSIONS: Recombinant human bone morphogenetic protein-2 maintained its osteoinductive capability in the presence of a chronic infection, and this property was enhanced by systemic antibiotic. This study presents an intervention that may potentially accelerate fracture healing in the presence of infection and colonized hardware, thereby permitting earlier removal of the hardware, and more timely and effective treatment of infection.

In vitro comparison of bioresorbable and titanium anterior cervical plates in the immediate postoperative condition.

Bioresorbable plates have recently been used with anterior cervical discectomy and fusion (ACDF). Compared with metallic plates, bioresorbable plates provide segmental stabilization with minimal imaging artifact, eventual resorption, and increased load sharing. The objectives of the present study were to determine whether a bioresorbable plate can withstand simulated physiologic static and cyclic loading, to compare the reduction in flexibility provided by bioresorbable and titanium plates, and to quantify load sharing between the plate and spine with graft. Sixteen human cervical motion segments were tested to +/-2.5 Nm in flexion-extension, lateral bending, and axial rotation. Range of motion (ROM) was measured (1) in the intact state, (2) with ACDF without plating, (3) after addition of either a bioresorbable or titanium plate, and (4) after 500 cycles of combined flexion-extension and axial torsion. Load sharing was evaluated by applying the same fixed rotation both without and with the plate, and was calculated as the moment resisted by the uninstrumented ACDF expressed as a percentage of the plated ACDF state. No plate failures or graft migration occurred during testing. Compared with the uninstrumented ACDF, bioresorbable plates reduced mean ROM by 49% in flexion-extension and 25% in lateral bending, with very little change in torsion. Titanium plates reduced uninstrumented ACDF ROM by 69% in flexion-extension, 45% in lateral bending, and 27% in torsion. Differences between bioresorbable and titanium plates were significant in flexion-extension and lateral bending. Cyclic loading did not significantly change ROM for either plate. More moment was shared in lateral bending by the spine/graft with bioresorbable plates (78%) compared with titanium plating (63%). Bioresorbable plates contained an intervertebral graft, provided some stabilization, remained intact throughout the simulated immediate postoperative loading, and shared more load with the graft and osteoligamentous spine than titanium plates.

Recombinant human osteogenic protein-1 induces bone formation in a chronically infected, internally stabilized segmental defect in the rat femur.

BACKGROUND: Recombinant human osteogenic protein-1 (rhOP-1), combined with a collagen carrier, has been shown to induce new-bone formation in a variety of animal models. The purpose of the present investigation was to test the hypotheses that rhOP-1 would accelerate bone formation in an internally stabilized, chronically infected, critical-size defect in the rat femur and that this effect would be enhanced by the administration of systemic antibiotic. METHODS: A 6-mm segmental defect was created surgically, stabilized with a polyacetyl plate and six Kirschner wires, and contaminated with 10(4) colony-forming units of Staphylococcus aureus in one femur in each of 168 Sprague-Dawley rats. After two weeks, these infected defects were débrided surgically and were assigned to one of six treatment groups. The defects in the thirty animals in the first group received lyophilized collagen carrier mixed with 200 microg of rhOP-1 dissolved in buffer, the defects in the thirty animals in the second group received carrier with 20 microg of rhOP-1 in buffer, and the defects in the twenty-four control animals in the third group received carrier mixed with buffer without rhOP-1. The last three groups were treated identically to the first three groups, except that the animals also received the antibiotic ceftriaxone for twenty-eight days after débridement. The animals were killed at two, four, eight, or twelve weeks after débridement. Newly mineralized callus within the defect, and adjacent to and bridging the outside of the defect, was assessed with use of quantitative high-resolution radiography, microcomputed tomography, torsional failure testing, and histological analysis of undecalcified sections. RESULTS: Bacterial cultures confirmed the presence of a chronic infection during the study period in all animals. At the later time-points, significantly more newly mineralized callus was present within and adjacent to the débrided defects that had been treated with 200 microg of rhOP-1, whereas minimal amounts of callus were present within and adjacent to the defects that had been treated without rhOP-1 and with 20 microg of rhOP-1. At eight and twelve weeks after débridement, there was significantly more newly mineralized callus in the group that had been treated with 200 microg of rhOP-1 with antibiotic than in the group that had been treated with 200 microg of rhOP-1 without antibiotic (p < 0.05). At twelve weeks, the values for torque, energy to failure, and linear stiffness for femora that had been treated with 200 microg of rhOP-1 with antibiotic were not significantly different from the values for intact, contralateral control femora, whereas the values for femora that had been treated with 200 microg of rhOP-1 without antibiotic remained significantly lower than those for the intact, contralateral controls (p < 0.05). CONCLUSIONS: Recombinant human osteogenic protein-1 maintained its osteoinductive capability in the presence of chronic infection, and this property was enhanced by antibiotic therapy. No substantial callus formed in the infected defects without a sufficiently high dose of rhOP-1. CLINICAL RELEVANCE: The treatment of an infection at the site of a fracture often necessitates removal of internal fixation. However, internal fixation is needed for fracture stability. This study presents an intervention that may accelerate fracture-healing in the presence of infection and colonized hardware, thereby permitting earlier removal of the hardware and more timely and effective treatment of the infection.

Precooling an acetabular liner makes its insertion into a metal shell easier.

Temporary shrinkage of an acetabular polyethylene liner due to precooling could reduce the force required to snap the liner into its metal shell. This study documented cooling and heating rates of liners with a particular locking mechanism design, determined forces required to seat liners in their shells as a function of temperature, and quantified the force surgeons can exert with their thumbs when seating a liner. It took up to 8 minutes to cool 58- and 70-mm liners in an ice-water bath from room temperature to near 0 degrees C, and up to 24 minutes to subsequently warm these liners to near body temperature. Forces required to seat liners were greater at room and body temperatures than at 0 degrees C. Liners precooled to 0 degrees C required insertion forces that could be generated manually by surgeons.

Validation, reliability, and complications of a tethering scoliosis model in the rabbit.

This study was conducted to refine a small animal model of scoliosis, and to quantify the deformities throughout its growth period. Subcutaneous scapula-to-contralateral pelvis tethering surgery was selected due to its minimally invasive nature and potential applicability for a large animal model. The procedure was performed in 7-week-old New Zealand white rabbits. Group A animals (n=9) underwent the tethering procedure with a suture that spontaneously released. Group B animals (n=17) had the identical procedure with a robust tether and pelvic fixation, which was maintained for 2 months during growth. All animals developed immediate post-operative scoliosis with a Cobb angle of 23 degrees (range, 6-39 degrees) in group A and 59 degrees (range, 24-90 degrees) in group B animals. During the 2 month post-tethering, group A animals lost their tether and scoliosis resolved, whereas all animals in group B maintained their tether until scheduled release at which time the mean scoliosis was 62 degrees. Immediately after tether release, group B scoliosis decreased to a mean 53 degrees. Over the following 4 months of adolescent growth, the scoliosis decreased to a mean of 43 degrees at skeletal maturity; the decrease usually occurred in animals with less than 45 degrees curves at tether release. Radiographs revealed apical vertebral wedging (mean 19 degrees ) in all group B animals. Sagittal spinal alignment was also assessed, and for group B animals, the scoliotic segment developed mild to moderate kyphosis (mean 28 degrees) and torsional deformity, but the kyphosis resolved by 4 months after tether-release. Complications specific to this technique included a high rate of transient scapulothoracic dissociation and cases of cor pulmonale. In conclusion, this tethering technique in immature rabbits consistently produced scoliosis with vertebral wedging when the tether was intact through the first 2 months of the protocol. The transient exaggeration of kyphosis suggests that the production of scoliosis is not necessarily dependent on lordosis in this model. Because this technique does not violate thoracic or spinal tissues, it may be useful in the investigation of secondary physiologic effects of mechanically-induced scoliosis, and may be scalable to larger animal species.

In vitro, biomechanical comparison of an anterior lumbar interbody fusion with an anteriorly placed, low-profile lumbar plate and posteriorly placed pedicle screws or translaminar screws.

STUDY DESIGN: An in vitro biomechanical comparison of anteriorly placed lumbar plates, pedicle screws, and translaminar screws in the anterior lumbar interbody fusion (ALIF) setting. OBJECTIVES: To determine whether an anteriorly placed lumbar plate reduces the flexibility in terms of neutral zone and range of motion of a simulated ALIF, and to compare this reduction in flexibility to that provided by posteriorly placed pedicle screws and translaminar screws. SUMMARY OF BACKGROUND DATA: Pedicular and translaminar facet fixation add stability and increase fusion rates, compared with ALIF alone. An anteriorly placed lumbar plate has been introduced to provide stability without the need for a secondary approach. However, this plate has not been evaluated biomechanically. METHODS: Seven intact, cadaveric lumbar motion segments were tested to +/- 7.5 Nm in flexion-extension, lateral bending, and axial torsion. Specimens were retested after ALIF, and after subsequent instrumentation with pedicle screws, translaminar screws, and anterior lumbar plates. The range of motion and neutral zone were measured from resulting flexibility curves. RESULTS: Mean (+/- standard deviation) flexion-extension range of motion for intact segments (9.9 degrees +/- 3.1 degrees ) was significantly reduced to 7.7 degrees +/- 1.8 degrees after ALIF (P = 0.02), and was further reduced to 3.0 degrees +/- 0.9 degrees with lumbar plates (P < 0.001), 1.5 degrees +/- 0.6 degrees with pedicle screws (P < 0.001), and 0.9 degrees +/- 0.4 degrees with translaminar screws (P < 0.001). All 3 devices also reduced flexion-extension neutral zone and torsion neutral zone and range of motion, compared with ALIF alone (P < 0.05). Lumbar plates did not decrease lateral bending range of motion or neutral zone (P > 0.05), whereas pedicle and translaminar screws did (P < 0.05). CONCLUSIONS: Although not as rigid as pedicle or translaminar screws, anterior lumbar plating does add significant stability to an ALIF and may provide a valuable, single-approach alternative to supplemental posterior fixation.

Characterization of a chronic infection in an internally-stabilized segmental defect in the rat femur.

The aim of this study was to characterize a new model of chronic osteomyelitis with clinically relevant features. A segmental defect of critical size was surgically created in the rat femur, stabilized with a polyacetyl plate and Kirschner wires, and contaminated with bacteria. The animals were allowed to recover while the contamination progressed to a chronic infection. At a later point in time, the defect was surgically débrided without removing the implant. Further treatments of interest, such as antibiotic therapy or application of an osteogenic agent, could be introduced at this time. To implement this model, an initial experiment was performed to determine the bacterial inoculum and time from contamination that would reliably result in an infected defect without causing excessive bone damage by the time débridement surgery was performed. The number of recovered bacteria, degree of radiographic bony lysis, and torsional stiffness of the defect fixation were measured in 192 rats as a function of 4 inocula of Staphylococcus aureus (10(3), 10(4), 10(5) or 10(6) CFUs) and 4 times from contamination (1, 2, 3 or 4 weeks). A 10(4) CFU inoculum over 2 weeks was found to consistently create an infection without severe lysis and loss of fixation stability. Based on these values, a second experiment was performed in 96 rats to characterize the débrided defect over time (2, 4, 8 and 12 weeks after débridement), with and without 4 weeks of the antibiotic ceftriaxone, in terms of the same outcome variables. Infection was persistent in all animals in spite of débridement and antibiotic therapy. Antibiotic therapy did not reduce the degree of bony lysis. Compared with animals not given antibiotic, bacterial counts significantly decreased during the period of antibiotic therapy, but then rebounded to significantly higher levels at 12 weeks. This model allows us to perform further studies on differing regimens of antibiotic therapy and their relationship to surgical débridement, and on the efficacy of osteogenic agents in the presence of infection.

Posterior augmentation of an anterior lumbar interbody fusion: minimally invasive fixation versus pedicle screws in vitro.

STUDY DESIGN: An in vitro biomechanical comparison of four posterior fixation techniques in the setting of an anterior lumbar interbody fusion (ALIF). OBJECTIVE: To compare the initial stability, in terms of range of motion and neutral zone, provided by pedicle screws, facet screws, translaminar facet screws, and H-graft plus interspinous cables in the presence of an anteriorly placed femoral ring allograft. SUMMARY OF BACKGROUND DATA: Pedicular fixation has been used to increase ALIF fusion rates but has also been linked with increased morbidity. Alternative posterior fixation options are available, but comprehensive biomechanical comparisons of these techniques do not exist. METHODS.: Twelve cadaveric lumbar motion segments were loaded to 5 Nm in unconstrained flexion-extension, lateral bending, and axial torsion. Specimens were tested intact, after ALIF, and after applying pedicle screws, translaminar screws, facet screws, and H-graft plus cables. The resulting neutral zones and ranges of motion were measured. RESULTS: The mean (+/-SEM) range of motion for each construct in flexion-extension was as follows: intact: 6.39 degrees (+/-0.47 degrees); ALIF alone: 3.31 degrees (+/-0.22 degrees); (ALIF+) pedicle screws: 0.6 degrees (+/-0.06 degrees); facet screws: 0.75 degrees (+/-0.12 degrees); translaminar screws: 0.61 degrees (+/-0.09 degrees); and H-graft: 1.74 degrees (+/-0.26 degrees). Pedicle, translaminar facet, and facet screws significantly decreased range of motion and neutral zone compared to ALIF alone in flexion-extension, lateral bending, and axial torsion (all at P < 0.04, except translaminar screws in torsion neutral zone where P = 0.09). H-graft decreasedflexion-extension range of motion and neutral zone only (P < 0.01) and resulted in a significantly greater neutral zone than pedicle and facet screws in torsion and lateral bending neutral zones (P < 0.03). CONCLUSIONS: In the ALIF setting, facet screw and translaminar screw techniques, which may be associated with less morbidity than pedicle screws clinically, provided initial posterior stabilization similar to pedicular fixation in this in vitro study.

Osteogenic protein-1 induces bone formation in the presence of bacterial infection in a rat intramuscular osteoinduction model.

OBJECTIVE: Evaluate the ability of osteogenic protein-1 to induce formation of de novo bone in the presence of bacterial infection and metal in an intramuscular osteoinduction model in the rat. DESIGN: Prospective experimental design with assessment time points of up to 4 weeks. SETTING: Intramuscular pocket surgically created along each side of the spine. ANIMALS: One-hundred-twenty adult male Sprague-Dawley rats. INTERVENTIONS: Each intramuscular pocket received 0, 10, or 25 microg of osteogenic protein-1 combined with a lyophilized collagen carrier, and 0 or 5 x 10 colony-forming units of Staphylococcus aureus. Pockets in 48 animals received a metal implant. Animals were killed at 1, 2, 3, or 4 weeks. MAIN OUTCOME MEASUREMENTS: High-resolution radiographs of resulting nodules of bone/soft tissue were digitized, and areas of newly formed bone were quantified using an image analysis workstation. The nodules were decalcified for histology, and calcium content of the decalcifying solution was quantified by flame atomic absorption spectrophotometry. RESULTS: There were minimal levels of calcium and area of new bone formation in nodules from pockets containing collagen carrier without osteogenic protein-1, for both infection and noninfection conditions. Calcium content and area of newly formed bone were significantly greater: 1) in infected pockets with osteogenic protein-1, compared to infected pockets without osteogenic protein-1; and 2) in noninfected pockets with osteogenic protein-1, compared to infected pockets with osteogenic protein-1. The presence of metal did not have a significant effect. CONCLUSION: Osteogenic protein-1 maintained its osteoinductive capability in a contaminated intramuscular pocket in the rat, albeit at a lower level than without infection. This finding supports further study using a more clinically realistic model.

Osteogenic protein-1 induced bone formation in an infected segmental defect in the rat femur.

The goal of this study was to use a segmental defect model in the rat femur to determine if osteogenic protein-1 (OP-1) is capable of inducing bone formation in the presence of bacterial contamination. A 6 mm segmental defect was surgically created and stabilized with a polyacetyl plate and Kirschner wires in one femur in each of 126 Sprague-Dawley rats. The animals were divided into eight groups in which the defect was either left untreated, or subjected to various combinations of OP-1 (11 or 50 microg), lyophilized bovine type I collagen (carrier for the OP-1), and 10(5) colony-forming units of Staphylococcus aureus. The animals were euthanized at either 2, 4, or 9 weeks. Quantitative radiographic and histologic analyses were performed on the harvested tissue. The initial contamination progressed to infection in all animals receiving bacteria, as determined by qualitative bacteriology. There was very little, if any, bone formation in the untreated defects, and in the contaminated defects with or without collagen carrier. Bone formation was significantly greater in contaminated defects with either dose of OP-1, compared with contaminated defects without OP-1. The 50 microg dose of OP-1 induced significantly more bone formation than the 11 microg dose, both with and without bacteria. This investigation has demonstrated that OP-1 maintains its osteoinductive capability in a contaminated segmental defect. OP-1 may potentially be used in the clinical management of contaminated fractures.

In vitro stability of cemented and cementless femoral stems with compaction.

Rigidity of initial fixation is a key factor contributing to the longevity of cemented and cementless femoral components in total hip arthroplasty. The objective of this study was to measure the initial stability of primary cemented and cementless femoral components under load when 15 pairs of cadaveric femurs were prepared by outward compaction of femoral cancellous bone in situ or by conventional extraction broaching. Three-dimensional micromotion was measured at proximal and distal locations on the femoral components using a device with spherical targets and linear variable differential transformers. External loads simulating the stance phases of level walking and stair ascent were applied to the femoral components by a materials test machine. Bone preparation method significantly affected each of the translation and rotation components of micromotion with cemented and cementless fixation. Micromotion with broaching was consistently greater than with compaction. Compared with compaction, the magnitude of the micromotion translation vector for broaching was an average of 3.9 (standard deviation, 3.1) times greater with cemented fixation, and an average of 2.3 (standard deviation, 1.4) times greater with cementless fixation. The results of this study showed the effectiveness of compaction of femoral cancellous bone in improving the initial stability of cemented and cementless femoral components in primary total hip arthroplasty.