Kirk C. McGilvray

Augmentation of a Rotator Cuff Suture Repair Using rhPDGF-BB and a Type I Bovine Collagen Matrix in an Ovine Model

Background Rotator cuff tears are a common source of shoulder pain. High rates (20%-94%) of structural failure of the repair have been attributed to multiple factors, including poor repair tissue quality and tendon-to-bone integration. Biologic augmentation using growth factors has potential to promote tendon-to-bone integration, improving the function and long-term success of the repair. One such growth factor is platelet-derived growth factor–BB (PDGF-BB), which has been shown to improve healing in tendon and bone repair models. Hypothesis Recombinant human PDGF-BB (rhPDGF-BB) combined with a highly porous type I bovine collagen matrix will improve the biomechanical function and morphologic appearance of the repair in a dose-dependent manner, relative to a suture-only control, after 12 weeks in an acute ovine model of rotator cuff repair. Study Design Controlled laboratory study. Methods An interpositional graft consisting of rhPDGF-BB and a type I collagen matrix was implanted in an ovine model of rotator cuff repair. Biomechanical and histologic analyses were performed to determine the functional and anatomic characteristics of the repair after 12 weeks. Results A significant increase in the ultimate load to failure was observed in repairs treated with 75 μg (1490.5 ± 224.5 N, P = .029) or 150 μg (1486.6 ± 229.0 N, P = .029) of rhPDGF-BB, relative to suture-only controls (910.4 ± 156.1 N) and the 500-μg rhPDGF-BB group (677.8 ± 105.9 N). The 75-μg and 150-μg rhPDGF-BB groups also exhibited increased tendon-to-bone inter-digitation histologically. No differences in inflammation or cellularity were observed among treatments. Conclusion This study demonstrated that an interpositional graft consisting of rhPDGF-BB (75 or 150 μg) and a type I collagen matrix was able to improve the biomechanical strength and anatomic appearance in an ovine model of rotator cuff repair compared to a suture-only control and the 500-μg rhPDGF-BB group. Clinical Relevance Recombinant human PDGF-BB combined with a type I collagen matrix has potential to be used to augment surgical repair of rotator cuff tears, thereby improving clinical success.

Biomechanical Analysis of an Ovine Rotator Cuff Repair via Porous Patch Augmentation in a Chronic Rupture Model

Background Rotator cuff repair is a commonly performed procedure, but many of these repairs fail in the postoperative term. Despite advances in surgical methods to optimize the repair, failure rates still persist clinically, thereby suggesting the need for novel mechanical or biological augmentation strategies. Nonresorbable implants provide an appealing approach because patch materials may confer acute mechanical stability and act as a conductive scaffold for tissue ingrowth at the site of the tendon insertion. Hypothesis The polyurethane scaffold mesh will confer greater biomechanical function relative to a nonaugmented repair after 12 weeks in vivo using a chronic ovine model of rotator cuff repair. Study Design Controlled laboratory study. Methods After development of the chronic rupture model, the tensile failure properties of the nonresorbable mesh-augmented repair (n, 9) were compared with those of a surgical control in an ovine model (n, 8). Results Rotator cuff repair with the scaffold mesh in the chronic model resulted in a significant 74.2% increase in force at failure relative to the nonaugmented surgical control (P = .021). Apparent increases in stiffness (55.4%) and global displacement at failure (21.4%) in the mesh-augmented group relative to nonaugmented controls were not significant (P = .126 and P = .123, respectively). At the study endpoint, the augmented shoulders recovered 37.8% and 40.7% of the force at failure and stiffness, respectively, of intact, nonoperated controls. Conclusion Using the previously described chronic rupture model, this study demonstrated that repair of a chronic tendon tear with the polyurethane scaffold mesh provides greater mechanical strength in the critical healing period than that of traditional suture anchor repair. Clinical Relevance This device could be used to enhance the surgical repair of the rotator cuff and consequently improve long-term clinical outcome.

Pedicle screw placement in the lumbar spine: effect of trajectory and screw design on acute biomechanical purchase.

OBJECT Low bone mineral density in patients undergoing lumbar spinal surgery with screws is an especially difficult challenge because poor bone quality can severely compromise the maximum achievable purchase of the screws. A relatively new technique, the cortical bone screw trajectory, utilizes a medialized trajectory in the caudocephalad direction to engage a greater amount of cortical bone within the pars interarticularis and pedicle. The objectives of this cadaveric biomechanical study were to 1) evaluate a cortical screw system and compare its mechanical performance to the traditional pedicle screw system; 2) determine differences in bone quality associated with the cortical screw trajectory versus the normal pedicle screw insertion technique; 3) determine the cortical wall breach rate with both the cortical and traditional screw trajectories; and 4) determine the performance of the traditional screw in the cortical screw trajectory. METHODS Fourteen fresh frozen human lumbar spine sections (L1-5) were used in this study (mean age 57 ± 19 years). The experimental plan involved drilling and tapping screw holes for 2 trajectories under navigation (a traditional pedicle screw and a cortical screw) in both high-and low-quality vertebrae, measuring the bone quality associated with these trajectories, placing screws in the trajectories, and evaluating the competence of the screw purchase via 2 mechanical tests (pullout and toggle). The 3 experimental variants were 1) traditional pedicle screws placed in the traditional pedicle screw trajectory, 2) traditional pedicle screws placed in the cortical screw trajectory, and 3) cortical screws placed in the cortical screw trajectory. RESULTS A statistically significant increase in bone quality was observed for the cortical trajectories with a cortical screw (42%; p < 0.001) and traditional pedicle screw (48%; p < 0.001) when compared to the traditional trajectory with a traditional pedicle screw within the high-quality bone group. These significant differences were also found in the lowquality bone cohort. All mechanical parameter comparisons (screw type and trajectory) between high-quality and lowquality samples were significant (p < 0.01), and these data were all linearly correlated (r ≥ 0.65) to bone mineral density. Not all mechanical parameters determined from pullout and toggle testing were statistically significant between the 3 screw/trajectory combinations. The incidence of cortical wall breach with the cortical or traditional pedicle screw trajectories was not significantly different. CONCLUSIONS The data demonstrated that the cortical trajectory provides denser bone that allows for utilization of smaller screws to obtain mechanical purchase that is equivalent to long pedicle screws placed in traditional pedicle screw trajectories for both normal- and low-quality bone. Overall, this biomechanical study in cadavers provides evidence that the cortical screw trajectory represents a good option to obtain fixation for the lumbar spine with low-quality bone.

A biomechanical analysis of venous tissue in its normal and post-phlebitic conditions

Although biomechanical studies of the normal rat vein wall have been reported (Weizsacker, 1988; Plante, 2002), there are no published studies that have investigated the mechanical effects of thrombus formation on murine venous tissue. In response to the lack of knowledge concerning the mechanical consequences of thrombus resolution, distinct thrombus-induced changes in the biomechanical properties of the murine vena cava were measured via biaxial stretch experiments. These data served as input for strain energy function (SEF) fitting and modeling (Gasser et al., 2006). Statistical differences were observed between healthy and diseased tissue with respect to the structural coefficient that represents the response of the non-collagenous, isotropic ground substance. Alterations following thrombus formation were also noted for the SEF coefficient which describes the anisotropic contribution of the fibers. The data indicate ligation of the vena cava leads to structural alterations in the ground substance and collagen fiber network.

Deformation of the equine pelvis in response to in vitro 3D sacroiliac joint loading.

REASONS FOR PERFORMING STUDY Sacroiliac joint injuries can cause poor performance; however, the interaction between pelvic mechanics and the sacroiliac joint is poorly understood. OBJECTIVE To measure pelvic displacement during 3D sacroiliac joint loading. METHODS Nine reflective triads were attached rigidly to bony prominences in sacropelvic specimens harvested from 14 horses for stereophotogrammetric analysis of triad displacements and joint kinematics. The sacrum was coupled to a load cell and mounted vertically within a material testing system (MTS). A pneumatic actuator was used to apply 90 Nm moments to the ischial arch to simulate nutation-counternutation and left and right lateral bending of the sacroiliac joints. Axial rotation of the sacrum was induced by torsion of the upper MTS fixture. Vectors of marker displacement within orthogonal planes of motion were measured during loading of the sacropelvic specimens. Comparisons in the magnitude and direction of triad displacements were made between paired left-right markers and paired loading conditions. RESULTS Nutation-counternutation of the sacroiliac joint caused vertical displacement of the ischial tuberosities and cranial-caudal displacement of the wings of the ilium. Lateral bending induced rotational displacement within the horizontal plane of all pelvic landmarks, relative to the sacrum. Axial rotation of the sacrum caused elevation of the wing of the ilium ipsilateral to the direction of sacral rotation and depression of the contralateral ilial wing. Significant paired left-right differences occurred during most sacroiliac joint loading conditions. Comparable magnitudes of pelvic displacement were measured during nutation-counternutation, left and right lateral bending, and left and right axial rotation. CONCLUSIONS The equine pelvis is not a rigid structure and asymmetric pelvic deformation occurs during most sacroiliac joint movements. CLINICAL RELEVANCE Bony pelvic deformation should be considered a normal response to any sacroiliac joint movement.

Implantable microelectromechanical sensors for diagnostic monitoring and post-surgical prediction of bone fracture healing.

The relationship between modern clinical diagnostic data, such as from radiographs or computed tomography, and the temporal biomechanical integrity of bone fracture healing has not been well‐established. A diagnostic tool that could quantitatively describe the biomechanical stability of the fracture site in order to predict the course of healing would represent a paradigm shift in the way fracture healing is evaluated. This paper describes the development and evaluation of a wireless, biocompatible, implantable, microelectromechanical system (bioMEMS) sensor, and its implementation in a large animal (ovine) model, that utilized both normal and delayed healing variants. The in vivo data indicated that the bioMEMS sensor was capable of detecting statistically significant differences (p‐value <0.04) between the two fracture healing groups as early as 21 days post‐fracture. In addition, post‐sacrifice micro‐computed tomography, and histology data demonstrated that the two model variants represented significantly different fracture healing outcomes, providing explicit supporting evidence that the sensor has the ability to predict differential healing cascades. These data verify that the bioMEMS sensor can be used as a diagnostic tool for detecting the in vivo course of fracture healing in the acute post‐treatment period.

Partial gravity unloading inhibits bone healing responses in a large animal model

The reduction in mechanical loading associated with space travel results in dramatic decreases in the bone mineral density (BMD) and mechanical strength of skeletal tissue resulting in increased fracture risk during spaceflight missions. Previous rodent studies have highlighted distinct bone healing differences in animals in gravitational environments versus those during spaceflight. While these data have demonstrated that microgravity has deleterious effects on fracture healing, the direct translation of these results to human skeletal repair remains problematic due to substantial differences between rodent and human bone. Thus, the objective of this study was to investigate the effects of partial gravitational unloading on long-bone fracture healing in a previously-developed large animal Haversian bone model. In vivo measurements demonstrated significantly higher orthopedic plate strains (i.e. load burden) in the Partial Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28-day healing period due to inhibited healing in the reduced loading environment. DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4 times lower than that of the FL Group (p<0.01), while µCT and histomorphometry demonstrated reduced periosteal callus area (p<0.05), mineralizing surface (p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as increased periosteal osteoclast number (p<0.05). These data provide strong evidence that the mechanical environment dramatically affects the fracture healing cascade, and likely has a negative impact on Haversian system healing during spaceflight.

An In Vivo Ovine Model of Bone Tissue Alterations in Simulated Microgravity Conditions

Microgravity and its inherent reduction in body-weight associated mechanical loading encountered during spaceflight have been shown to produce deleterious effects on important human physiological processes. Rodent hindlimb unloading is the most widely-used ground-based microgravity model. Unfortunately, results from these studies are difficult to translate to the human condition due to major anatomic and physiologic differences between the two species such as bone microarchitecture and healing rates. The use of translatable ovine models to investigate orthopedic-related conditions has become increasingly popular due to similarities in size and skeletal architecture of the two species. Thus, a new translational model of simulated microgravity was developed using common external fixation techniques to shield the metatarsal bone of the ovine hindlimb during normal daily activity over an 8 week period. Bone mineral density, quantified via dual-energy X-ray absorptiometry, decreased 29.0% (p < 0.001) in the treated metatarsi. Post-sacrifice biomechanical evaluation revealed reduced bending modulus (-25.8%, p < 0.05) and failure load (-27.8%, p < 0.001) following the microgravity treatment. Microcomputed tomography and histology revealed reduced bone volume (-35.9%, p < 0.01), trabecular thickness (-30.9%, p < 0.01), trabecular number (-22.5%, p < 0.05), bone formation rate (-57.7%, p < 0.01), and osteoblast number (-52.5%, p < 0.001), as well as increased osteoclast number (269.1%, p < 0.001) in the treated metatarsi of the microgravity group. No significant alterations occurred for any outcome parameter in the Sham Surgery Group. These data indicate that the external fixation technique utilized in this model was able to effectively unload the metatarsus and induce significant radiographic, biomechanical, and histomorphometric alterations that are known to be induced by spaceflight. Further, these findings demonstrate that the physiologic mechanisms driving bone remodeling in sheep and humans during prolonged periods of unloading (specifically increased osteoclast activity) are more similar than previously utilized models, allowing more comprehensive investigations of microgravity-related bone remodeling as it relates to human spaceflight.

Bony ingrowth potential of 3D-printed porous titanium alloy: a direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model

BACKGROUND CONTEXT: There is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that three-dimensional (3D)-printed interbody cages using porous titanium material can provide more consistent bone ingrowth and biological fixation. PURPOSE: The purpose of this study was to provide an evidence-based approach to decisionmaking regarding interbody materials for spinal fusion. STUDY DESIGN: A comparative animal study was performed. METHODS: A skeletally mature ovine lumbar fusion model was used for this study. Interbody fusions were performed at L2-L3 and L4-L5 in 27 mature sheep using three different interbody cages (ie, polyetheretherketone [PEEK], plasma sprayed porous titanium-coated PEEK [PSP], and 3D-printed porous titanium alloy cage [PTA]). Non-destructive kinematic testing was performed in the three primary directions of motion. The specimens were then analyzed using micro-computed tomography (μ-CT); quantitative measures of the bony fusion were performed. Histomorphometric analyses were also performed in the sagittal plane through the interbody device. Outcome parameters were compared between cage designs and time points. RESULTS: Flexion-extension range of motion (ROM) was statistically reduced for the PTA group compared with the PEEK cages at 16 weeks (p-value=.02). Only the PTA cages demonstrated a statistically significant decrease in ROM and increase in stiffness across all three loading directions between the 8-week and 16-week sacrifice time points (p-value≤.01). Micro-CT data demonstrated significantly greater total bone volume within the graft window for the PTA cages at both 8 weeks and 16 weeks compared with the PEEK cages (p-value<.01). CONCLUSIONS: A direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, μ-CT, and histologic performance in an ovine model. The 3Dprinted porous titanium interbody cage resulted in statistically significant reductions in ROM, increases in the bone ingrowth profile, as well as average construct stiffness compared with PEEK and PSP.

Evaluation of a polyetheretherketone (PEEK) titanium composite interbody spacer in an ovine lumbar interbody fusion model: biomechanical, microcomputed tomographic, and histologic analyses

BACKGROUND CONTEXT The most commonly used materials used for interbody cages are titanium metal and polymer polyetheretherketone (PEEK). Both of these materials have demonstrated good biocompatibility. A major disadvantage associated with solid titanium cages is their radiopacity, limiting the postoperative monitoring of spinal fusion via standard imaging modalities. However, PEEK is radiolucent, allowing for a temporal assessment of the fusion mass by clinicians. On the other hand, PEEK is hydrophobic, which can limit bony ingrowth. Although both PEEK and titanium have demonstrated clinical success in obtaining a solid spinal fusion, innovations are being developed to improve fusion rates and to create stronger constructs using hybrid additive manufacturing approaches by incorporating both materials into a single interbody device. PURPOSE The purpose of this study was to examine the interbody fusion characteristic of a PEEK Titanium Composite (PTC) cage for use in lumbar fusion. STUDY DESIGN/SETTING Thirty-four mature female sheep underwent two-level (L2-L3 and L4-L5) interbody fusion using either a PEEK or a PTC cage (one of each per animal). Animals were sacrificed at 0, 8, 12, and 18 weeks post surgery. MATERIALS AND METHODS Post sacrifice, each surgically treated functional spinal unit underwent non-destructive kinematic testing, microcomputed tomography scanning, and histomorphometric analyses. RESULTS Relative to the standard PEEK cages, the PTC constructs demonstrated significant reductions in ranges of motion and a significant increase in stiffness. These biomechanical findings were reinforced by the presence of significantly more bone at the fusion site as well as ingrowth into the porous end plates. CONCLUSIONS Overall, the results indicate that PTC interbody devices could potentially lead to a more robust intervertebral fusion relative to a standard PEEK device in a clinical setting.