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Because intubation-mediated cervical spine and spinal cord injury are likely determined by intubation force magnitude, understanding the determinants of intubation force magnitude is clinically relevant. With direct (Macintosh) laryngoscopy, when glottic view is less favorable, anesthesiologists apply greater force. We hypothesized that, when compared with direct (Macintosh) laryngoscopy, intubation force with an optical indirect laryngoscope (Airtraq) would be less dependent on glottic visualization.Using data obtained in a prior clinical study, we tested whether the slope of the intubation force versus glottic view relationship differed between intubations performed in 14 patients who were intubated twice, once with a Macintosh and once with an Airtraq videolaryngoscope. Slopes were compared using least-squares linear regression and robust regression.The slope of the intubation force (N) versus glottic view (%) relationship with the Macintosh (-0.679 [standard error {SE}, 0.147]) was significantly more negative than that of the Airtraq (-0.076 [SE, 0.246]). The least-squares regression difference in slopes was -0.603 (SE, 0.287); P = .046. The robust regression difference in slopes was -0.747 (SE, 0.187); P = .0005. Thus, when compared with the Macintosh, intubation force magnitude with Airtraq laryngoscopy was less dependent on glottic visualization.Previously, we reported that intubation force with the Airtraq was less in magnitude compared with the Macintosh. Our current study adds that intubation force also is less dependent on glottic view with Airtraq compared with the Macintosh.

The increasing evidence of stress-strain hysteresis in large animal or human myocardium calls for extensive characterizations of the passive viscoelastic behavior of the myocardium. Several recent studies have investigated and modeled the viscoelasticity of the left ventricle while the right ventricle (RV) viscoelasticity remains poorly understood. Our goal was to characterize the biaxial viscoelastic behavior of RV free wall (RVFW) using two modeling approaches. We applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) theories to experimental stress relaxation data from healthy adult ovine. A three-term Prony series relaxation function combined with an Ogden strain energy density function was used in the QLV modeling, while a power-law formulation was adopted in the NLV approach. The ovine RVFW exhibited an anisotropic and strain-dependent viscoelastic behavior relative to anatomical coordinates, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. From the QLV fitting, the relaxation term associated with the largest time constant played the dominant role in the overall relaxation behavior at most strains from early to late diastole, whereas the term associated with the smallest time constant was pronounced only at low strains at early diastole. From the NLV fitting, the parameters showed a nonlinear dependence on the strain. Overall, our study characterized the anisotropic, nonlinear viscoelasticity to capture the elastic and viscous resistances of the RVFW during diastole. These findings deepen our understanding of RV myocardium dynamic mechanical properties. STATEMENT OF SIGNIFICANCE: Although significant progress has been made to understand the passive elastic behavior of the right ventricle free wall (RVFW), its viscoelastic behavior remains poorly understood. In this study, we originally applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) models to published experimental data from healthy ovine RVFW. Our results revealed an anisotropic and strain-dependent viscoelastic behavior of the RVFW. The parameters from the NLV fitting showed nonlinear relationships with the strain, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. These findings characterize the anisotropic, nonlinear viscoelasticity of RVFW to fully capture the total (elastic and viscous) resistance that is critical to diastolic function.

BACKGROUND The purpose of this study was to evaluate the mechanical, structural, and histologic quality of rotator cuff repairs augmented with an interposition electrospun nanofiber scaffold composed of polyglycolic acid (PGA) and poly-L-lactide-co-e-caprolactone (PLCL) in an acute sheep model. METHODS Forty acute infraspinatus tendon detachment and repair procedures were performed in a sheep infraspinatus model using a double-row transosseous-equivalent anchor technique either with an interposition nanofiber scaffold composed of polyglycolic acid-poly-L-lactide-co-e-caprolactone or with no scaffold. Animals were euthanized at the 6-week (20 samples) and 12-week (20 samples) postoperative time points to assess the biomechanical and histologic properties of the repairs and to compare differences within each group. RESULTS Within the scaffold-treated group, there was a significant increase in ultimate failure force (in newtons) from 6 to 12 weeks (P < .01), a significant increase in ultimate failure load from 6 to 12 weeks (P < .01), and a significant increase in ultimate failure stress (in megapascals) from 6 to 12 weeks (P < .01). At 6 weeks, the tendon-bone attachment was most consistent with an "indirect" type of insertion, whereas at 12 weeks, a visible difference in the progression and re-formation of the enthesis was observed. Compared with controls, animals in the scaffold-treated group displayed an insertion of the fibrous tendon with the humeral footprint that was beginning to be organized in a manner similar to the "native" direct/fibrocartilaginous insertion of the ovine infraspinatus tendon. In the majority of these animals treated with the scaffold, prominent perforating collagen fibers, similar to Sharpey fibers, were present and extending through a region of calcified fibrocartilage and attaching to the humeral footprint. No surgical complications occurred in any of the 40 sheep, including delayed wound healing or infection. CONCLUSIONS In a sheep acute rotator cuff repair model, securing a nanofiber scaffold between the tendon and the bone using a double-row transosseous-equivalent anchor fixation technique resulted in greater failure strength. Additionally, at the enthesis, Sharpey fiber-like attachments (ie, collagen fibers extending from the tendon into the calcified fibrocartilage of the humerus) were observed, which were not seen in the control group.

To develop an in vivo experimental model for bone marrow lesions (BMLs) in ovine femorotibial joints.Randomized, prospective experimental study.Eighteen healthy, skeletally-mature Dorper cross ewes.One medial femoral condyle was penetrated with a 1.1 mm pin, and the contralateral medial femoral condyle was treated with transcutaneous extracorporeal shockwave (ESW) at 0.39 ± 0.04 mJ/mmPin penetration induced a BML detected on MRI within 2 weeks and lasted at least 12 weeks. BMLs were not observed in ESW-treated condyles. Histologically, BMLs were characterized by hemorrhage and inflammatory cellular infiltrate, and progressed to more dense fibrous tissue over time. Pathological changes were not observed in the articular cartilage overlying the region of BMLs.Direct, focal trauma to all layers of the osteochondral unit was sufficient to create an experimentally-induced BML which persisted for at least 90 days. The protocol used for ESW in this study did not induce BMLs.Experimental induction of BMLs is possible and mimicked naturally occurring disease states. Volumetric imaging is a sensitive method for characterization of the dynamic nature of these lesions.

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Objective Rotator cuff tendon tears are the most common soft tissue injuries in the shoulder joint. Various animal models have been described for this condition, but all current translational animal models have inherent weaknesses in their ability to generate chronically degenerated rotator cuff tendons. The objective of this study was to evaluate a partial infraspinatus tendon transection model as a means of creating a chronically degenerated rotator cuff tendon in an ovine model and compare the injury characteristics of this model to those observed in human patients with severe chronic rotator cuff tendon injuries. Study Design The infraspinatus tendons of six sheep were partially detached followed by capping of the detached medial section of the tendon with Gore-Tex. Human tissue samples of the supraspinatus tendon were harvested from patients undergoing primary reverse shoulder arthroplasty and served as positive controls of chronic rotator cuff tendinopathy. Results Transected sheep tendons were characterized predominantly by an acute reactive and reparative pathological process as compared with the chronic degenerative changes observed in the human tendons. In contrast, the non-transected portion of the ovine tendon showed histological changes, which were more chronic and degenerative in nature when compared with the transected tendon. Conclusion Overall, histological features of the non-transected portion of ovine tendon were more similar to those observed in the chronic degenerated human tendon.

Background The purpose of this study was to evaluate the biomechanical and histologic properties of rotator cuff repairs using a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA (poly( l -lactide-co-glycoside)) microfibers in an animal model compared to standard anchors in an ovine model. Methods Fifty-six (n = 56) skeletally mature sheep were randomly assigned to a repair of an acute infraspinatus tendon detachment using a innovative anchor-PLGA scaffold device (Treatment) or a similar anchor without the scaffold (Control). Animals were humanely euthanized at 7 and 12 weeks post repair. Histologic and biomechanical properties of the repairs were evaluated and compared. Results The Treatment group had a significantly higher fibroblast count at 7 weeks compared to the Control group. The tendon bone repair distance, percentage perpendicular fibers, new bone formation at the tendon-bone interface, and collagen type III deposition was significantly greater for the Treatment group compared with the Control group at 12 weeks (P ≤ .05). A positive correlation was identified in the Treatment group between increased failure loads at 12 weeks and the following parameters: tendon-bone integration, new bone formation, and collagen type III. No statistically significant differences in biomechanical properties were identified between Treatment and Control Groups (P > .05). Conclusions Use of a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA microfibers improves the histologic properties of rotator cuff repairs in a sheep model. Improved histology was correlated with improved final construct strength at the 12-week time point.

Background In a closed claims study, most patients experiencing cervical spinal cord injury had stable cervical spines. This raises two questions. First, in the presence of an intact (stable) cervical spine, are there tracheal intubation conditions in which cervical intervertebral motions exceed physiologically normal maximum values? Second, with an intact spine, are there tracheal intubation conditions in which potentially injurious cervical cord strains can occur? Methods This study utilized a computational model of the cervical spine and cord to predict intervertebral motions (rotation, translation) and cord strains (stretch, compression). Routine (Macintosh) intubation force conditions were defined by a specific application location (mid-C3 vertebral body), magnitude (48.8 N), and direction (70 degrees). A total of 48 intubation conditions were modeled: all combinations of 4 force locations (cephalad and caudad of routine), 4 magnitudes (50 to 200% of routine), and 3 directions (50, 70, and 90 degrees). Modeled maximum intervertebral motions were compared to motions reported in previous clinical studies of the range of voluntary cervical motion. Modeled peak cord strains were compared to potential strain injury thresholds. Results Modeled maximum intervertebral motions occurred with maximum force magnitude (97.6 N) and did not differ from physiologically normal maximum motion values. Peak tensile cord strains (stretch) did not exceed the potential injury threshold (0.14) in any of the 48 force conditions. Peak compressive strains exceeded the potential injury threshold (–0.20) in 3 of 48 conditions, all with maximum force magnitude applied in a nonroutine location. Conclusions With an intact cervical spine, even with application of twice the routine value of force magnitude, intervertebral motions during intubation did not exceed physiologically normal maximum values. However, under nonroutine high-force conditions, compressive strains exceeded potentially injurious values. In patients whose cords have less than normal tolerance to acute strain, compressive strains occurring with routine intubation forces may reach potentially injurious values. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

To minimize the risk of cervical spinal cord injury in patients who have cervical spine pathology, minimizing cervical spine motion during laryngoscopy and tracheal intubation is commonly recommended. However, clinicians may better aim to reduce cervical spinal cord strain during airway management of their patients. The aim of this study was to predict laryngoscope force characteristics (location, magnitude, and direction) that would minimize cervical spine motions and cord strains.We utilized a computational model of the adult human cervical spine and spinal cord to predict intervertebral motions (rotation [flexion/extension] and translation [subluxation]) and cord strains (stretch and compression) during laryngoscopy.Routine direct (Macintosh) laryngoscopy conditions were defined by a specific force application location (mid-C3 vertebral body), magnitude (48.8 N), and direction (70 degrees). Sixty laryngoscope force conditions were simulated using 4 force locations (cephalad and caudad of routine), 5 magnitudes (25-200% of routine), and 3 directions (50, 70, 90 degrees).Under all conditions, extension at Oc-C1 and C1-C2 were greater than in all other cervical segments. Decreasing force magnitude to values reported for indirect laryngoscopes (8-17 N) decreased cervical extension to ~50% of routine values. The cervical cord was most likely to experience potentially injurious compressive strain at C3, but force magnitudes ≤50% of routine (≤24.4 N) decreased strain in C3 and all other cord regions to non-injurious values. Changing laryngoscope force locations and directions had minor effects on motion and strain.The model predicts clinicians can most effectively minimize cervical spine motion and cord strain during laryngoscopy by decreasing laryngoscope force magnitude. Very low force magnitudes (5 N, ~10% of routine) are necessary to decrease overall cervical extension to50% of routine values. Force magnitudes ≤24.4 N (≤50% of routine) are predicted to help prevent potentially injurious compressive cord strain.

Background context While the clinical effectiveness of recombinant human Platelet Derived Growth Factor-B chain homodimer combined with collagen and β-tricalcium phosphate (rhPDGF-BB + collagen/β-TCP) treatment for indications involving hindfoot and ankle is well-established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard. Purpose The purpose of this study was to compare the effects of rhPDGF-BB + collagen/β-TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/β-TCP treatments using biomechanical, radiographic, and histological assessment techniques. Study design Thirty-two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF-BB + collagen/β-TCP matrix in a lumbar spinal fusion model. Interbody polyetheretherketone (PEEK) cages contained either autograft, rhPDGF-BB + collagen/β-TCP, collagen/β-TCP matrix, or left empty. Methods Animals were sacrificed 8- or 16-weeks post-surgery. Spinal fusion was evaluated via post-sacrifice biomechanical, micro-computed tomography (μCT), and histological analysis. Outcomes were statistically compared using a two-way analysis of variance (ANOVA) with an alpha value of 0.05 and a Tukey post-hoc test. Results There were no statistically significant differences between groups within treatment timepoints for flexion-extension, lateral bending, or axial rotation range of motion, neutral zone, neutral zone stiffness, or elastic zone stiffness. μCT bone volume fraction was significantly greater between treatment groups independent of timepoint where Autograft and rhPDGF-BB + collagen/β-TCP treatments demonstrated significantly greater bone volume fraction as compared to collagen/β-TCP (P = .026 and P = .038, respectively) and Empty cage treatments (P = .002 and P = .003, respectively). μCT mean bone density fraction was most improved in rhPDGF-BB + collagen/β-TCP specimens at the 8 week and 16-week timepoints as compared to all other treatment groups. There were no statistically significant differences in histomorphometric measurements of bone, soft tissue, or empty space between rhPDGF-BB + collagen/β-TCP and autograft treatments. Conclusions The results of this study indicate that the use of rhPDGF-BB combined with collagen/β-TCP promotes spinal fusion comparable to that of autograft bone. Clinical significance The data indicate that rhPDGF-BB combined with collagen/β-TCP promotes spinal fusion comparably to autograft bone treatment and may offer a viable alternative in large animal spinal fusion. Future prospective clinical studies are necessary to fully understand the role of rhPDGF-BB combined with collagen/β-TCP in human spinal fusion healing.

Background In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue‐level mechanical properties, it is intractable to experimentally measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modeling the CME in TE scaffolds using the finite element method. Methods A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells. Results The multi‐axial loading modality predicted the greatest percentage of cell volumes falling within the CME target envelope (%PTE) in the study (65 %PTE for 5.0% equibiaxial tensile strain with 50 kPa radial‐direction compression; 7.6 %PTE without radial pressure). Additionally, the architectural scale had a moderate influence on the CME (maximum of 17 %PTE), with minimal change in the tissue‐level properties of the scaffold. Scaffold materials and architectures had secondary influences on the predicted regeneration by modifying the tissue‐level scaffold mechanics. Conclusions Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly. This study facilitated an improved understanding of the relationship between tissue‐level and cell‐level mechanics to drive anabolic cell responses for tissue regeneration., In this study, the cellular micromechanical environment in tissue engineering scaffolds was modeled using the finite element method. A repeating unit of composite fiber scaffold for annulus fibrosus (AF) repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The distribution of CME in the scaffold was predicted and compared to proposed target mechanics based on anabolic responses of AF cells. Scaffold loading modality was identified as the critical factor for TE the AF. Scaffold materials and architecture were also predicted to modulate the scaffold loading and, therefore, control the CME indirectly.

OBJECTIVE: To compare the geometrical properties and bone mineral density (BMD) of the proximal radius between Saint Bernard and other giant breed dogs. STUDY DESIGN: Observational, cross‐sectional, descriptive study. ANIMALS: Thirteen client‐owned Saint Bernard dogs and 13 other client‐owned giant breed dogs. METHODS: Computed tomography (CT) studies of Saint Bernard and other giant breed dogs were reviewed. Multiplanar reconstruction of the CT images was used to determine cross‐sectional variables at the proximal half of the radius, including mean cortical thickness (mCT) and moment of inertia (MOI). Cortical BMD was estimated from Hounsfield unit measurements at each cross‐section and averaged per bone. One‐way analysis of variance was used to detect differences between groups. RESULTS: Proximal radii of Saint Bernard dogs had a lower cortical/medullary ratio (1.75 vs 2.2, P

Current diagnostic modalities, such as radiographs or computed tomography, exhibit limited ability to predict the outcome of bone fracture healing. Failed fracture healing after orthopaedic surgical treatments are typically treated by secondary surgery; however, the negative correlation of time between primary and secondary surgeries with resultant health outcome and medical cost accumulation drives the need for improved diagnostic tools. This study describes the simultaneous use of multiple (n = 5) implantable flexible substrate wireless microelectromechanical (fsBioMEMS) sensors adhered to an intramedullary nail (IMN) to quantify the biomechanical environment along the length of fracture fixation hardware during simulated healing in ex vivo ovine tibiae. This study further describes the development of an antenna array for interrogation of five fsBioMEMS sensors simultaneously, and quantifies the ability of these sensors to transmit signal through overlaying soft tissues. The ex vivo data indicated significant differences associated with sensor location on the IMN (p

Rapid prediction of adverse bone fracture healing outcome (e.g., nonunion and/or delayed union) is essential to advise adjunct therapies to reduce patient suffering and improving healing outcome. Radiographic diagnostic methods remain ineffective during early healing, resulting in average nonunion diagnosis times surpassing six months. To address this clinical deficit, we developed a novel diagnostic device to predict fracture healing outcome by noninvasive telemetric measurements of fracture bending stiffness. This study evaluated the hypothesis that our diagnostic antenna system is capable of accurately measuring temporal fracture healing stiffness, and advises the utility of this data for expedited prediction of healing outcomes during early (≤3 weeks) fracture recovery.Fracture repair was simulated, in reverse chronology, by progressively destabilizing cadaveric ovine metatarsals (n=8) stabilized via locking plate fixation. Bending stiffness of each fracture state were predicted using a novel direct electromagnetic coupling diagnostic system, and results were compared to values from material testing (MT) methods. While direct calculation of fracture stiffness in a simplistic cadaver model is possible, comparable analysis of the innumerable permutations of fracture and treatment type is not feasible. Thus, clinical feasibility of direct electromagnetic coupling was explored by parametric finite element (FE) analyses (n=1,632 simulations). Implant mechanics were simulated throughout the course of healing for cases with variations to fracture size, implant type, implant structure, and implant material.For all fracture states, stiffness values predicted by the direct electromagnetic coupling system were not significantly different than those quantified byThis technology demonstrates potential as a noninvasive clinical tool to accurately quantify healing fracture stiffness to augment and expedite healing outcome predictions made using radiographic imaging.

BACKGROUND CONTEXT Screw loosening is a prevalent failure mode in orthopedic hardware, particularly in osteoporotic bone or revision procedures where the screw-bone engagement is limited. PURPOSE The objective of this study was to evaluate the efficacy of a novel screw retention technology (SRT) in an ovine lumbar fusion model. STUDY DESIGN/SETTING This was a biomechanical, radiographic, and histologic study utilizing an ovine lumbar spine model. METHODS : In total, 54 (n=54) sheep lumbar spines (L2–L3) underwent posterior lumbar fusion (PLF) via pedicle screw fixation, connecting rod, and bone graft. Following three experimental variants were investigated: positive control (ideal clinical scenario), negative control (simulation of compromised screw holes), and SRT treatments. Biomechanical and histologic analyses of the functional spinal unit (FSU) were determined as a function of healing time (0, 3, and 12 months postoperative). RESULTS Screw pull-out, screw break-out, and FSU stability of the SRT treatments were generally equivalent to the positive control group and considerably better than the negative control group. Histomorphology of the SRT treatment screw region of interest (ROI) observed an increase in bone percentage and decrease in void space during healing, consistent with ingrowth at the implant interface. The PLF ROI observed similar bone percentage throughout healing between the SRT treatment and positive control. Less bone formation was observed for the negative control. CONCLUSIONS The results of this study demonstrate that the SRT improved screw retention and afforded effective FSU stabilization to achieve solid fusion in an otherwise compromised fixation scenario in a large animal model.

BACKGROUND: Expedient prediction of adverse bone fracture healing (delayed- or non-union) is necessary to advise secondary treatments for improving healing outcome to minimize patient suffering. Radiographic imaging, the current standard diagnostic, remains largely ineffective at predicting nonunions during the early stages of fracture healing resulting in mean nonunion diagnosis times exceeding six months. Thus, there remains a clinical deficit necessitating improved diagnostic techniques. It was hypothesized that adverse fracture healing expresses impaired biological progression at the fracture site, thus resulting in reduced temporal progression of fracture site stiffness which may be quantified prior to the appearance of radiographic indicators of fracture healing (i.e., calcified tissue). METHODS: A novel multi-location direct electromagnetic coupling antenna was developed to diagnose relative changes in the stiffness of fractures treated by metallic orthopaedic hardware. The efficacy of this diagnostic was evaluated during fracture healing simulated by progressive destabilization of cadaveric ovine metatarsals treated by locking plate fixation (n=8). An ovine in vivo comparative fracture study (n=8) was then utilized to better characterize the performance of the developed diagnostic in a clinically translatable setting. In vivo measurements using the developed diagnostic were compared to weekly radiographic images and postmortem biomechanical, histological, and micro computed tomography analyses. RESULTS: For all cadaveric samples, the novel direct electromagnetic coupling antenna displayed significant differences at the fracture site (P

In vivo bioreactors are a promising approach for engineering vascularized autologous bone grafts to repair large bone defects. In this pilot parametric study, we first developed a three-dimensional (3D) printed scaffold uniquely designed to accommodate inclusion of a vascular bundle and facilitate growth factor delivery for accelerated vascular invasion and ectopic bone formation. Second, we established a new sheep deep circumflex iliac artery (DCIA) model as an in vivo bioreactor for engineering a vascularized bone graft and evaluated the effect of implantation duration on ectopic bone formation. Third, after 8 weeks of implantation around the DCIA, we transplanted the prevascularized bone graft to a 5 cm segmental bone defect in the sheep tibia, using the custom 3D printed bone morphogenic protein 2 (BMP-2) loaded scaffold without prior in vivo bioreactor maturation as a control. Analysis by micro-computed tomography and histomorphometry found ectopic bone formation in BMP-2 loaded scaffolds implanted for 8 and 12 weeks in the iliac pouch, with greater bone formation occurring after 12 weeks. Grafts transplanted to the tibial defect supported bone growth, mainly on the periphery of the graft, but greater bone growth and less soft tissue invasion was observed in the avascular BMP-2 loaded scaffold implanted directly into the tibia without prior in vivo maturation. Histopathological evaluation noted considerably greater vascularity in the bone grafts that underwent in vivo maturation with an inserted vascular bundle compared with the avascular BMP-2 loaded graft. Our findings indicate that the use of an initial DCIA in vivo bioreactor maturation step is a promising approach to developing vascularized autologous bone grafts, although scaffolds with greater osteoinductivity should be further studied. IMPACT STATEMENT: This translational pilot study aims at combining a tissue engineering scaffold strategy, in vivo prevascularization, and a modified transplantation technique to accelerate large segmental bone defect repair. First, we three-dimensional (3D) printed a 5 cm scaffold with a unique design to facilitate vascular bundle inclusion and osteoinductive growth factor delivery. Second, we established a new sheep deep circumflex iliac artery model as an in vivo bioreactor for prevascularizing the novel 3D printed osteoinductive scaffold. Subsequently, we transplanted the prevascularized bone graft to a clinically relevant 5 cm segmental bone defect in the sheep tibia for bone regeneration.

Ventricle dysfunction is the most common cause of heart failure, which leads to high mortality and morbidity. The mechanical behavior of the ventricle is critical to its physiological function. It is known that the ventricle is anisotropic and viscoelastic. However, the understanding of ventricular viscoelasticity is much less than that of its elasticity. Moreover, the left and right ventricles (LV&RV) are different in embryologic origin, anatomy, and function, but whether they distinguish in viscoelastic properties is unclear. We hypothesized that passive viscoelasticity is different between healthy LVs and RVs. Ex vivo cyclic biaxial tensile mechanical tests (1, 0.1, 0.01 Hz) and stress relaxation (strain of 3, 6, 9, 12, 15%) were performed for ventricles from healthy adult sheep. Outflow track direction was defined as the longitudinal direction. Hysteresis stress–strain loops and stress relaxation curves were obtained to quantify the viscoelastic properties. We found that the RV had more pronounced frequency-dependent viscoelastic changes than the LV. Under the physiological frequency (1 Hz), the LV was more anisotropic in the elasticity and stiffer than the RV in both directions, whereas the RV was more anisotropic in the viscosity and more viscous than the LV in the longitudinal direction. The LV was quasi-linear viscoelastic in the longitudinal but not circumferential direction, and the RV was nonlinear viscoelastic in both directions. This study is the first to investigate passive viscoelastic differences in healthy LVs and RVs, and the findings will deepen the understanding of biomechanical mechanisms of ventricular function.

Purpose/Aim: Expanded, human connective tissue cells can adopt mesenchymal stromal cell (MSC) properties that are favorable for applications in regenerative medicine. Sheep are used as a large anim...

Cell fate in tissue engineering (TE) strategies is paramount to regenerate healthy, functional organs. The mechanical loads experienced by cells play an important role in cell fate. However, in TE scaffolds with a cell-laden hydrogel matrix, it is prohibitively complex to prescribe and measure this cellular micromechanical environment (CME). Accordingly, this study aimed to develop a finite element (FE) model of a TE scaffold unit cell that can be subsequently implemented to predict the CME and cell fates under prescribed loading. The compressible hyperelastic mechanics of a fibrin hydrogel were characterized by fitting unconfined compression and confined compression experimental data. This material model was implemented in a unit cell FE model of a TE scaffold. The FE mesh and boundary conditions were evaluated with respect to the mechanical response of a region of interest (ROI). A compressible second-order reduced polynomial hyperelastic model gave the best fit to the experimental data (C10 = 1.72 × 10−4, C20 = 3.83 × 10−4, D1 = 3.41, D2 = 8.06 × 10−2). A mesh with seed sizes of 40 µm and 60 µm in the ROI and non-ROI regions, respectively, yielded a converged model in 54 min. The in-plane boundary conditions demonstrated minimal influence on ROI mechanics for a 2-by-2 unit cell. However, the out-of-plane boundary conditions did exhibit an appreciable influence on ROI mechanics for a two bilayer unit cell. Overall, the developed unit cell model facilitates the modeling of the mechanical state of a cell-laden hydrogel within a TE scaffold under prescribed loading. This model will be utilized to characterize the CME in future studies, and 3D micromechanical criteria may be applied to predict cell fate in these scaffolds.

There have been recent investigations into developing disc replacements and regenerative medicine to treat internal derangements of the temporomandibular joint (TMJ) disc. Previous attempts at disc replacements have faced challenges related in part to a limited understanding of the TMJ's complex mechanical environment. The purpose of this study was to characterize the mechanical behavior of the ovine TMJ disc and to derive viscoelastic constitutive models from the experimental data. Fresh ovine TMJ discs were tested in indentation stress-relaxation tests on the inferior surface, uniaxial tension tests to failure, and dynamic biaxial tensile tests. Results showed an order of magnitude stiffer behavior in tension in the anteroposterior (primary fiber) direction compared to the mediolateral direction. The stiffness in tension was much greater than in compression. Regional comparisons showed greater elastic moduli in indentation in the posterior and anterior bands compared to the central region. A hyper-viscoelastic constitutive model captured the dynamic stress-stretch behavior in both indentation and biaxial tension with good agreement. These data will support ongoing and future computational modeling of local TMJ mechanics, aid in biomaterials identification, and ultimately enhance development of implant designs for TMJ disc replacement.

Cell fate in tissue engineering (TE) strategies is paramount to regenerate healthy, functional organs. The mechanical loads experienced by cells play an important role in cell fate. However, in TE scaffolds with a cell-laden hydrogel matrix, it is prohibitively complex to prescribe and measure this cellular micromechanical environment (CME). Accordingly, this study aimed to develop a finite element (FE) model of a TE scaffold unit cell that can be subsequently implemented to predict the CME and cell fates under prescribed loading. The compressible hyperelastic mechanics of a fibrin hydrogel were characterized by fitting unconfined compression and confined compression experimental data. This material model was implemented in a unit cell FE model of a TE scaffold. The FE mesh and boundary conditions were evaluated with respect to the mechanical response of a region of interest (ROI). A compressible second-order reduced polynomial hyperelastic model gave the best fit to the experimental data (C10 = 1.72×10-4, C20 = 3.83×10-4, D1 = 3.41, D2 = 8.06×10-2). A mesh with seed sizes of 40 μm and 60 μm in the ROI and non-ROI regions, respectively, yielded a converged model in 54 minutes. The in-plane boundary conditions demonstrated minimal influence on ROI mechanics for a 2-by-2 unit cell. However, the out-of-plane boundary conditions did exhibit an appreciable influence on ROI mechanics for a two bilayer unit cell. Overall, the developed unit cell model facilitates the modeling of the mechanical state of a cell-laden hydrogel within a TE scaffold under prescribed loading. This model will be utilized to characterize the CME in future studies, and 3D micromechanical criteria may be applied to predict cell fate in these scaffolds.

Objective Screw loosening in fracture fixation poses a clinical risk which may lead to implant failure, particularly in poor bone quality. The objective of this study was to examine the effectiveness of a novel screw retention technology (SRT) for increased screw purchase in a large animal metatarsal fracture model. Study Design This was a biomechanical, radiographic, and histological study utilizing an ovine metatarsal fracture model. Twenty-four sheep metatarsi underwent 3-mm ostectomies and were repaired with a nine-hole plate and 3.5-mm screws placed in oversized 3.5-mm holes to simulate worst case revision surgeries (i.e. no initial screw thread bone contact). Sheep were sacrificed at 3, 6 or 12 weeks (n = 6 each) post-operation. Post-sacrifice, each surgically implanted screw underwent either destructive mechanical testing or histomorphometric analyses. Results Treated metatarsi showed improved screw retention and normal fracture healing. Significant improvement in breakout strength and pullout strength of screws treated with the SRT were found as a function of healing time. Histologically, bone ingrowth at the screw interface was also shown to significantly increase with healing time. Improvements in fracture healing, indicated by an increase in bone fraction and decrease in void space at the osteotomy, were also observed with healing time. Conclusion The results demonstrate the effectiveness of the SRT as a method for improved screw retention in a rescue-screw type scenario.

In tissue engineering (TE) strategies, cell processes are regulated by mechanical stimuli. Although TE scaffolds have been developed to replicate tissue-level mechanical properties, it is experimentally prohibitive to measure and prescribe the cellular micromechanical environment (CME) generated within these constructs. Accordingly, this study aimed to fill this lack of understanding by modelling the CME in TE scaffolds using the finite element method. A repeating unit of composite fiber scaffold for annulus fibrosus repair with a fibrin hydrogel matrix was prescribed a series of loading, material, and architectural parameters. The CME was predicted and the corresponding cell phenotypes were predicted based on previously hypothesized criteria. Scaffold multi-axial loading was demonstrated as the most pertinent parameter contributing to the CME criteria being satisfied. Specifically, radial-direction compression with biaxial tension lead to a prediction of regeneration for 66.5% of the cell volumes. Additionally, the architectural scale had a moderate influence on the CME with minimal change in the tissue-level properties of the scaffold. All other scaffold materials and architectures considered had secondary influences on the predicted regeneration by modifying the scaffold loading. By predicting the regeneration potential of different scaffold designs, the developed high-fidelity computational tool described in this study enables for a more comprehensive understanding of the relationship between tissue-level and cell-level mechanics for a broad range of tissue engineering applications.

Despite efforts to simulate the in vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex vivo, the viscoelastic behavior of in vivo and ex vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex vivo and in vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex vivo samples experienced a higher stress and greater relaxation than in vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1–1 s). The results of this study underscore the necessity of utilizing material models developed from in vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in vivo model in future high-resolution finite element modeling efforts. Statement of Significance Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in vivo response). Therefore, this study directly compared the mechanical response of ex vivo and in vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex vivo data (which are easier to obtain) and emphasizes the importance of future in vivo experimental animal work.

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 decision-making 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 Conclusions A direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µ-CT, and histologic performance in an ovine model. The 3D-printed 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.

A promising approach for monitoring and predicting the course of bone fracture healing is by measuring the mechanical load-sharing between the healing callus and the implanted fixation hardware. Previous technologies have used implantable sensors which require modification to the fixation hardware and may carry long term biocompatibility risks. The objective of this paper was to optimize and evaluate a method of externally sensing hardware load-sharing based on the electromagnetic near field effects of a radio-frequency antenna. A series of parametric experiments was conducted to optimize the dimensional parameters of a coaxial dipole antenna to improve the antenna’s sensitivity to displacement of a metal plate. The results of the parametric tests guided the design of an optimized antenna, including a coiled loop antenna structure. The antenna was then evaluated for its efficacy in sensing the displacement of a metal plate as well as the deflection of an orthopaedic fracture fixation plate due to an applied load via physical experiments and computational simulations. The antenna’s resonant frequency was sensitive to the displacement of a metal plate, and followed an inverse-square relationship with plate distance. The antenna was also able to sense the bending deflection of the mechanically loaded fracture plate, with the resonant frequency following an approximately linear relationship with applied load. Computational finite-element electromagnetic predictions closely matched the experimental data. This method of sensing plate deflections may be effective for measuring the mechanical load sharing in fractured bones in order to monitor and predict the course of fracture healing.

Laryngoscopy and endotracheal intubation in patients with unstable cervical spines may cause pathological spinal motion and resultant cord injury. Cadaver and mathematical (finite element) models of a type II odontoid fracture predict C1-C2 motions during intubation to be of low magnitude, especially with the use of a low-force videolaryngoscope. Using continuous fluoroscopy, we recorded C1-C2 motion during C-MAC D videolaryngoscopy and intubation in 2 patients with type II odontoid fractures. In these 2 patients, C1-C2 extension and change in C1-C2 canal space were comparable to motions predicted by cadaver and finite element models and did not cause neurological injury.

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.

Background Cervical total disc replacement was developed to preserve motion and reduce adjacent-level degeneration relative to fusion, yet concerns remain that total disc replacement will lead to altered facet joint loading and long-term facet joint arthrosis. This study is intended to evaluate changes in facet contact force, pressure and surface area at the treated and superior adjacent levels before and after discectomy, disc replacement, and fusion. Methods Ten fresh-frozen human cadaveric cervical spines were potted from C2 to C7 with pressure sensors placed into the facet joints of C3–C4 and C4–C5 via slits in the facet capsules. Moments were applied to the specimens to produce axial rotation, lateral bending and extension. Facet contact force and pressure were measured at both levels for intact, discectomy at C4–C5, disc replacement with ProDisc-C (Synthes Spine, West Chester, Pennsylvania, USA) at C4–C5, and anterior discectomy and fusion with Cervical Spine Locking Plate (Synthes Spine, West Chester, Pennsylvania, USA) at C4–C5. Facet contact area was calculated from the force and pressure measurements. An analysis of variance was used to determine significant differences with P -values Findings Facet contact force was elevated at the treated level under extension following both discectomy and disc replacement, while facet contact pressure and area were relatively unchanged. Facet contact force and area were decreased at the treated level following fusion for all three loading conditions. Interpretation Total disc replacement preserved facet contact force for all scenarios except extension at the treated level, highlighting the importance of the anterior disco-ligamentous complex. This could promote treated-level facet joint disease.

Computational models of the brain rely on accurate constitutive relationships to model the viscoelastic behavior of brain tissue. Current viscoelastic models have been derived from experiments conducted in a single direction at a time and therefore lack information on the effects of multiaxial loading. It is also unclear if the time-dependent behavior of brain tissue is dependent on either strain magnitude or the direction of loading when subjected to tensile stresses. Therefore, biaxial stress relaxation and cyclic experiments were conducted on corpus callosum tissue isolated from fresh ovine brains. Results demonstrated the relaxation behavior to be independent of strain magnitude, and a quasi-linear viscoelastic (QLV) model was able to accurately fit the experimental data. Also, an isotropic reduced relaxation tensor was sufficient to model the stress-relaxation in both the axonal and transverse directions. The QLV model was fitted to the averaged stress relaxation tests at five strain magnitudes while using the measured strain history from the experiments. The resulting model was able to accurately predict the stresses from cyclic tests at two strain magnitudes. In addition to deriving a constitutive model from the averaged experimental data, each specimen was fitted separately and the resulting distributions of the model parameters were reported and used in a probabilistic analysis to determine the probability distribution of model predictions and the sensitivity of the model to the variance of the parameters. These results can be used to improve the viscoelastic constitutive models used in computational studies of the brain.