Bone marrow stromal cells generate an osteoinductive microenvironment when cultured on titanium-aluminum-vanadium substrates with biomimetic multiscale surface roughness.

Osseointegration of titanium-based implants possessing complex macroscale/microscale/mesoscale/nanoscale (multiscale) topographies support a direct and functional connection with native bone tissue by promoting recruitment, attachment and osteoblastic differentiation of bone marrow stromal cells (MSCs). Recent studies show that the MSCs on these surfaces produce factors, including bone morphogenetic protein 2 (BMP2) that can cause MSCs not on the surface to undergo osteoblast differentiation, suggesting they may produce an osteogenic environmentin vivo. This study examined if soluble factors produced by MSCs in contact with titanium-aluminum-vanadium (Ti6Al4V) implants possessing a complex multiscale biomimetic topography are able to induce osteogenesis ectopically. Ti6Al4V disks were grit-blasted and acid-etched to create surfaces possessing macroscale and microscale roughness (MM), micro/meso/nanoscale topography (MN), and macro/micro/meso/nanoscale topography (MMNTM). Polyether-ether-ketone (PEEK) disks were also fabricated by machining to medical-grade specifications. Surface properties were assessed by scanning electron microscopy, contact angle, optical profilometry, and x-ray photoelectron spectroscopy. MSCs were cultured in growth media (GM). Proteins and local factors in their conditioned media (CM) were measured on days 4, 8, 10 and 14: osteocalcin, osteopontin, osteoprotegerin, BMP2, BMP4, and cytokines interleukins 6, 4 and 10 (IL6, IL4, and IL10). CM was collected from D14 MSCs on MMNTMand tissue culture polystyrene (TCPS) and lyophilized. Gel capsules containing active demineralized bone matrix (DBM), heat-inactivated DBM (iDBM), and iDBM + MMN-GM were implanted bilaterally in the gastrocnemius of athymic nude mice (N= 8 capsules/group). Controls included iDBM + GM; iDBM + TCPS-CM from D5 to D10 MSCs; iDBM + MMN-CM from D5 to D10; and iDBM + rhBMP2 (R&D Systems) at a concentration similar to D5-D10 production of MSCs on MMNTMsurfaces. Legs were harvested at 35D. Bone formation was assessed by micro computed tomography and histomorphometry (hematoxylin and eosin staining) with the histology scored according to ASTM 2529-13. DNA was greatest on PEEK at all time points; DNA was lowest on MN at early time points, but increased with time. Cells on PEEK exhibited small changes in differentiation with reduced production of BMP2. Osteoblast differentiation was greatest on the MN and MMNTM, reflecting increased production of BMP2 and BMP4. Pro-regenerative cytokines IL4 and IL10 were increased on Ti-based surfaces; IL6 was reduced compared to PEEK. None of the media from TCPS cultures was osteoinductive. However, MMN-CM exhibited increased bone formation compared to iDBM and iDBM + rhBMP2. Furthermore, exogenous rhBMP2 alone, at the concentration found in MMN-CM collected from D5 to D10 cultures, failed to induce new bone, indicating that other factors in the CM play a critical role in that osteoinductive microenvironment. MSCs cultured on MMNTMTi6Al4V surfaces differentiate and produce an increase in local factors, including BMP2, and the CM from these cultures can induce ectopic bone formation compared to control groups, indicating that the increased bone formation arises from the local response by MSCs to a biomimetic, multiscale surface topography.

Influence of spinal lordosis correction location on proximal junctional failure: a biomechanical study.

STUDY DESIGN: Assessment of sagittal lordosis distribution on mechanical proximal junctional failure-related risks through computer-based biomechanical models. OBJECTIVE: To biomechanically assess how lordosis distribution influences radiographical and biomechanical indices related to Proximal Junctional Failure (PJF). The "optimal" patient-specific targets to restore the sagittal balance in posterior spinal fusion are still not known. Among these, the effect of the lumbar lordosis correction strategy on complications such as PJF remain uncertain. METHODS: In this computational biomechanical study, five adult spinal deformity patients who underwent posterior spinal fixation were retrospectively reviewed. Their surgery, first erect posture and flexion movement were simulated with a patient-specific multibody model. Three pedicle subtraction osteotomy (PSO) levels (L3, L4, and L5) were simulated, with consistent global lordosis for a given patient and pelvic tilt adjusted accordingly to the actual surgery. Computed loads on the anterior spine and instrumentation were analyzed and compared using Kruskal-Wallis statistical tests and Spearman correlations. RESULTS: In these models, no significant correlations were found between the lordosis distribution index (LDI), PSO level and biomechanical PJF-related indices. However, increasing the sagittal vertical axis (SVA) and thoracolumbar junction angle (TLJ) and decreasing the sacral slope (SS) increased the bending moment sustained by the rods at the proximal instrumented level (r = 0.52, 0.57, - 0.56, respectively, p < 0.05). There was a negative correlation between SS and the bending moment held by the adjacent proximal segment (r = - 0.71, p < 0.05). CONCLUSION: Based on these biomechanical simulations, there was no correlation between the lordosis distribution and PJF-associated biomechanical factors. However, increasing SS and flattening the TLJ, as postural adjustment strategies required by a more distal PSO, did decrease such PJF-related factors. Sagittal restoration and PJF risks remain multifactorial, and the use of patient-specific biomechanical models may help to better understand the complex interrelated mechanisms.

Lordosis Recreation in Transforaminal and Posterior Lumbar Interbody Fusion: A Cadaveric Study of the Influence of Surgical Bone Resection and Cage Angle.

STUDY DESIGN: Controlled cadaveric study of surgical technique in transforaminal and posterior lumbar interbody fusion (TLIF and PLIF) OBJECTIVE.: To evaluate the contribution of surgical techniques and cage variables in lordosis recreation in posterior interbody fusion (TLIF/PLIF). SUMMARY OF BACKGROUND DATA: The major contributors to lumbar lordosis are the lordotic lower lumbar discs. The pathologies requiring treatment with segmental fusion are frequently hypolordotic or kyphotic. Current posterior based interbody techniques have a poor track record for recreating lordosis, although recreation of lordosis with optimum anatomical alignment is associated with better outcomes and reduced adjacent segment change needing revision. It is unclear whether surgical techniques or cage parameters contribute significantly to lordosis recreation. METHODS: Eight instrumented cadaveric motion segments were evaluated with pre and post experimental radiological assessment of lordosis. Each motion segment was instrumented with pedicle screw fixation to allow segmental stabilization. The surgical procedures were unilateral TLIF with an 18° lordotic and 27 mm length cage, unilateral TLIF (18°, 27 mm) with bilateral facetectomy, unilateral TLIF (18°, 27 mm) with posterior column osteotomy (PCO), PLIF with bilateral cages (18°, 22 mm), and PLIF with bilateral cages (24°, 22 mm). Cage insertion used and "insert and rotate" technique. RESULTS: Pooled results demonstrated a mean increase in lordosis of 2.2° with each procedural step (lordosis increase was serially 1.8°, 3.5°, 1.6°, 2.5°, and 1.6° through the procedures). TLIF and PLIF with PCO increased lordosis significantly compared with unilateral TLIF and TLIF with bilateral facetectomy. The major contributors to lordosis recreation were PCO, and PLIF with paired shorter cages rather than TLIF. CONCLUSION: This study demonstrates that the surgical approach to posterior interbody surgery influences lordosis gain and PCO optimizes lordosis gain in TLIF. The bilateral cages used in PLIF are shorter and associated with further gain in lordosis. This information has the potential to aid surgical planning when attempting to recreate lordosis to optimize outcomes. LEVEL OF EVIDENCE: N/A.

Computed tomography-guided tissue engineering of upper airway cartilage.

Normal laryngeal function has a large impact on quality of life, and dysfunction can be life threatening. In general, airway obstructions arise from a reduction in neuromuscular function or a decrease in mechanical stiffness of the structures of the upper airway. These reductions decrease the ability of the airway to resist inspiratory or expiratory pressures, causing laryngeal collapse. We propose to restore airway patency through methods that replace damaged tissue and improve the stiffness of airway structures. A number of recent studies have utilized image-guided approaches to create cell-seeded constructs that reproduce the shape and size of the tissue of interest with high geometric fidelity. The objective of the present study was to establish a tissue engineering approach to the creation of viable constructs that approximate the shape and size of equine airway structures, in particular the epiglottis. Computed tomography images were used to create three-dimensional computer models of the cartilaginous structures of the larynx. Anatomically shaped injection molds were created from the three-dimensional models and were seeded with bovine auricular chondrocytes that were suspended within alginate before static culture. Constructs were then cultured for approximately 4 weeks post-seeding and evaluated for biochemical content, biomechanical properties, and histologic architecture. Results showed that the three-dimensional molded constructs had the approximate size and shape of the equine epiglottis and that it is possible to seed such constructs while maintaining 75%+ cell viability. Extracellular matrix content was observed to increase with time in culture and was accompanied by an increase in the mechanical stiffness of the construct. If successful, such an approach may represent a significant improvement on the currently available treatments for damaged airway cartilage and may provide clinical options for replacement of damaged tissue during treatment of obstructive airway disease.

A transducer for measuring force on surgical sutures.

The objective of this study was to validate, both in vitro and in an ex vivo model, a technique for the measurement of forces exerted on surgical sutures. For this purpose, a stainless steel E-type buckle force transducer was designed and constructed. A strain gauge was mounted on the central beam of the transducer to measure transducer deformation. The transducer was tested and calibrated on a single strand of surgical suture during cyclic loading. Further validation was performed using a previously published cadaveric model of laryngoplasty in the horse. Linear regression of transducer output with actual force during calibration tests resulted in mean R² values of 1.00, 0.99, and 0.99 for rising slope, falling slope, and overall slope, respectively. The R² was not less than 0.96 across an average of 75 cycles per test. The difference between rising slope and falling slope was 4%. Over 45 846 samples, the predicted force from transducer output showed a mean error of 4%. In vitro validation produced an adjusted R² of 0.99 when the force on the suture was regressed against translaryngeal pressure in a mixed-effects model. E-type buckle force transducers showed a highly linear output over a physiological force range when applied to surgical suture in vitro and in an ex vivo model of laryngoplasty. With appropriate calibration and short-term in vivo implantation, these transducers may advance our knowledge of the mechanisms of success and failure of techniques, such as laryngoplasty, that use structural suture implants.

Cementless total hip replacement in an alpaca.

OBJECTIVE: To report management of a chronic slipped capital femoral epiphysis (SCFE) in an alpaca using cementless total hip replacement (THR). STUDY DESIGN: Case report. ANIMAL: An 18-month-old, 47 kg alpaca male. METHODS: Cementless THR was performed in an alpaca with a chronic, right SCFE, and secondary osteoarthritis. Force plate gait analysis was performed before and 8 weeks after surgery. Outcome was determined through clinical evaluation, radiography, and force plate gait analysis. RESULTS: Cementless THR resulted in marked improvement in the alpaca's comfort level, degree of lameness, and range of motion. On preoperative force plate gait analysis there was decreased contact time (P=.01) and vertical impulse (P<.01) of the affected limb, whereas at 8 weeks postoperatively significant differences in gait analysis between pelvic limbs were not apparent. CONCLUSION: THR using a BioMedtrix canine cementless modular prosthesis restored hip function in an alpaca with coxofemoral osteoarthritis from chronic SCFE. CLINICAL RELEVANCE: THR may be an appropriate treatment for selected traumatic and degenerative conditions of the coxofemoral joint in alpacas.

Simultaneous Determination of Tuning and Calibration Parameters for Computer Experiments.

Tuning and calibration are processes for improving the representativeness of a computer simulation code to a physical phenomenon. This article introduces a statistical methodology for simultaneously determining tuning and calibration parameters in settings where data are available from a computer code and the associated physical experiment. Tuning parameters are set by minimizing a discrepancy measure while the distribution of the calibration parameters are determined based on a hierarchical Bayesian model. The proposed Bayesian model views the output as a realization of a Gaussian stochastic process with hyperpriors. Draws from the resulting posterior distribution are obtained by the Markov chain Monte Carlo simulation. Our methodology is compared with an alternative approach in examples and is illustrated in a biomechanical engineering application. Supplemental materials, including the software and a user manual, are available online and can be requested from the first author.

Stemmed implants improve stability in augmented constrained condylar knees.

We previously combined experimental and computational measures to ascertain whether tibial stem augmentation reduces bone strains beneath constrained condylar implants. Using these same integrated approaches, we examined the benefit of a stem when a wedge is used. Implants were removed from the eight paired cadaver specimens from our previous experiment, and oblique defects created that were restored with 15 degrees metallic wedges cemented in place. We applied a varus moment and an axial load and monitored relative motion between implant and bone. Specimen-specific 3-D finite element models were constructed from CT scans and radiographs to examine bone stress in the proximal tibia. Implants with a wedge but no stem had greater motion than the previous control with no stem or wedge. Use of a modular stem with a wedge maintained the same level of motion as the primary case, suggesting that a stem is preferable when a wedge is utilized. The computational models confirmed this conclusion with a 30% reduction in bone stress compared to 17% in the primary case without a wedge. The wedge carried more axial load compared to the primary implant due to its support on stiff metaphyseal bone.

Image-guided tissue engineering of anatomically shaped implants via MRI and micro-CT using injection molding.

This study demonstrates for the first time the development of engineered tissues based on anatomic geometries derived from widely used medical imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Computer-aided design and tissue injection molding techniques have demonstrated the ability to generate living implants of complex geometry. Due to its complex geometry, the meniscus of the knee was used as an example of this technique's capabilities. MRI and microcomputed tomography (microCT) were used to design custom-printed molds that enabled the generation of anatomically shaped constructs that retained shape throughout 8 weeks of culture. Engineered constructs showed progressive tissue formation indicated by increases in extracellular matrix content and mechanical properties. The paradigm of interfacing tissue injection molding technology can be applied to other medical imaging techniques that render 3D models of anatomy, demonstrating the potential to apply the current technique to engineering of many tissues and organs.

Wear simulation of the ProDisc-L disc replacement using adaptive finite element analysis.

OBJECT: An understanding of the wear potential of total disc replacements (TDRs) is critical as these new devices are increasingly introduced into clinical practice. The authors analyzed the wear potential of a ProDisc-L implant using an adaptive finite element (FE) technique in a computational simulation representing a physical wear test. METHODS: The framework for calculating abrasive wear, first validated using a model of a total hip replacement (THR), was then used to model the ProDisc-L polyethylene component that is fixed to the inferior endplate and articulates with the rigid superior endplate. Proposed standards for spine wear testing protocols specified the inputs of flexion-extension (6/-3 degrees), lateral bending (+/- 2 degrees), axial twist (+/- 1.5 degrees), and axial load (200-1750 N or 600-2000 N) applied to the model through 10 million simulation cycles. The model was calibrated with a wear coefficient determined from an experimental wear test. Implicit FE analyses were then performed for variations in coefficient of friction, polyethylene elastic modulus, radial clearance, and polyethylene component thickness to investigate their effects on wear. RESULTS: Using the initial loading protocol (single-peaked axial load profile of 300-1750 N) from the experimental wear test, the polyethylene wear rate was 9.82 mg per million cycles. When a double-peaked loading profile (600-2000 N) was applied, the wear rate increased to 11.77 mg per million cycles. Parametric design variations produced only small changes in wear rates for this simulation. CONCLUSIONS: The chosen design variables had little effect on the resultant wear rates. The comparable wear rate for the THR validation analysis was 16.17 mg per million cycles, indicating that, using this framework, the wear potential of the TDR was equivalent to, if not better, than the THR using joint-specific loading standards.

Retrieval, experimental, and computational assessment of the performance of total knee replacements.

Wear mechanisms in polyethylene components for total knee replacements are inherently mechanical; the local stresses or strains exceed some material limit. Retrieval analysis and knee simulators have provided the means to quantify the damage observed in vivo or in vitro. These results have been circumstantially linked to the material stresses obtained from computational simulations using finite element analysis, knee simulator tests, and computational simulations of two condylar knee designs. We hypothesize that if an equivalent loading environment is produced in the computational simulation, we can correlate the distribution of computed stresses with observed damage of simulator specimens and further relate design differences to in vivo performance from retrieval analyses. The finite element model agreed with the knee simulator kinematics and kinetics within 2-13%, and composite FEA contact areas matched 66-90% of the damage areas due to burnishing on the simulator specimens. Burnishing was the primary mode of damage for both the simulator and retrieval specimens corresponding with the relatively low magnitudes of contact stress observed. Both the computational and experimental techniques underpredicted the amount determined from retrieval analysis, but the differences between the two designs were consistent for all three methods. Combining these techniques strengthens the applicability of the computational simulation while highlighting the complementary approach of these methods for preclinical testing and assessing the link between material state and damage.

Cancellous bone strains indicate efficacy of stem augmentation in constrained condylar knees.

Modular augmented stems of a constrained condylar knee implant are intended to improve tibial fixation under increased varus/valgus loads, but conflicting studies have not yet indicated the factors determining stem usage and performance. To address this, we combined a paired-tibiae, cadaveric experiment of unstemmed and stemmed tibial components with specimen-specific computational models. We hypothesized that the stem would improve implant stability by decreasing implant motion and compressive strains in the proximal cancellous bone due to load transfer by the stem. The models also would indicate the important factors governing stem performance. Large variations of the displacements arose because of loading and biologic variability indicating the inconclusive effects of a stem. Despite these variations, the models showed that a stem augment consistently decreased the strains (30%-50%) in the bone beneath the tray. In tibiae of sufficient stiffness, the supporting cancellous bone did not approach yield, suggesting that a stem augment may not always be necessary. On the other hand, tibial specimens with reduced bone quality and lower stiffness benefited from a stem augment that transferred load to the distal cortical bone. Therefore, patient selection and proper sizing of the implant were identified as important factors in the analyses.

Flat medial-lateral conformity in total knee replacements does not minimize contact stresses.

The potential for wear in UHMWPE components for total knee replacements can be reduced by decreasing the stresses and strains arising from tibial-femoral contact. The conformity of the articular surfaces has a large effect on the resultant stresses, and components that achieve flat medial-lateral contact have been assumed to produce the lowest stresses due to their perfect conformity. We computed the stresses arising from curved and flat contact on a half-space using two-dimensional, plane strain elasticity solutions and finite element analyses to compare the performance of curved and flat indenters. These indenters were represented by a polynomial so the profiles could be continuously varied from curved to flat. Curved contact resulted in maximum stresses at the center of contact, while flat contact produced maximum stresses at the edge of contact. In addition, three contemporary tibial configurations (flat-on-flat, curved-on-flat, and curved-on-curved geometries) were analyzed using the finite element method with nonlinear material properties. The maximum contact stress, von Mises stress, and von Mises strain were lowest for the curved-on-curved model. The other configurations resulted in higher contact stresses, von Mises stresses, and von Mises strains. The perfect conformity arising from flat contact did not reduce the contact stresses in the UHMWPE component. The tensile stresses, however, were lowest for the flat-on-flat geometry compared with the other two configurations. Relating these distinct differences could prove useful in interpretation of data from simulator and retrieval studies.