Shape fidelity, mechanical and biological performance of 3D printed polycaprolactone-bioactive glass composite scaffolds.

Direct ink writing (DIW) is a promising extrusion-based 3D printing technology, which employs an ink-deposition nozzle to fabricate 3D scaffold structures with customizable ink formulations for tissue engineering applications. However, determining the optimal DIW process parameters such as temperature, pressure, and speed for the specific ink is essential to achieve high reproducibility of the designed geometry and subsequent mechano-biological performance for different applications, particularly for porous scaffolds of finite sizes (total volume > 1000 mm3) and controlled pore size and porosity. The goal of this study was to evaluate the feasibility of fabricating Polycaprolactone (PCL) and bio-active glass (BG) composite-based 3D scaffolds of finite size using DIW. 3D-scaffolds were fabricated either as cylinders (10 mm diameter; 15 mm height) or cubes (5 × 5 × 5 mm3) with height/width aspect ratios of 1.5 and 1, respectively. A rheological characterization of the PCL-BG inks was performed before printing to determine the optimal printing parameters such as pressure and speed for printing at 110 °C. Microstructural properties of the scaffolds were analyzed in terms of overall scaffold porosity, and in situ pore size assessments in each layer (36 pores/layer; 1764 pores per specimen) during their fabrication. Measured porosity of the fabricated specimens-PCL: x¯ =46.94%, SD = 1.61; PCL-10 wt%BG: x¯ = 48.29%, SD = 5.95; and PCL-20 wt% BG: x¯=50.87%, SD = 2.45-matched well with the designed porosity of 50%. Mean pore sizes-PCL [x¯ = 0.37 mm (SD = 0.03)], PCL-10%BG [x¯ = 0.38 mm (SD = 0.07)] and PCL-20% BG [x¯ = 0.37 mm (SD = 0.04)]-were slightly fairly close to the designed pore size of 0.4 mm. Nevertheless there was a small but consistent, statistically significant (p < 0.0001) decrease in pore size from the first printed layer (PCL: 0.39 mm; PCL-10%BG: 0.4 mm; PCL-20%BG: 0.41 mm) to the last. SEM and micro-CT imaging revealed consistent BG particle distribution across the layers and throughout the specimens. Cell adhesion experiments revealed similar cell adhesion of PCL-20 wt% BG to pure PCL, but significantly better cell proliferation - as inferred from metabolic activity - after 7 days, although a decrease after 14 days was noted. Quasi-static compression tests showed a decrease in compressive yield strength and apparent elastic modulus with increasing BG fraction, which could be attributed to a lack of adequate mechanical bonding between the BG particles and the PCL matrix. The results show that the inks were successfully generated, and the scaffolds were fabricated with high resolution and fidelity despite their relatively large size (>1000 mm3). However, further work is required to understand the mechano-biological interaction between the BG particle additives and the PCL matrix to improve the mechanical and biological properties of the printed structures.

Effect of two types of shoulder prosthesis on the muscle forces using a generic multibody model for different arm motions.

BACKGROUND: This study aims to analyze the effects of a novel dual-bearing shoulder prosthesis and a conventional reverse shoulder prosthesis on the deltoid and rotator cuff muscle forces for four different arm motions. The dual-bearing prosthesis is a glenoid-sparing joint replacement with a moving center of rotation. It has been developed to treat rotator cuff arthropathy, providing an increased post-operative functionality. METHODS: A three-dimensional musculoskeletal OpenSim® model of an upper body, incorporating a natural gleno-humeral joint and a scapula-thoracic joint developed by Blana et al. (J Biomech 41: 1714-1721, 2008), was used as a reference for the natural shoulder. It was modified by integrating first a novel dual-bearing prosthesis, and second, a reverse shoulder prosthesis into the shoulder joint complex. Four different arm motions, namely abduction, scaption, internal and external rotation, were simulated using an inverse kinematics approach. For each of the three models, shoulder muscle forces and joint reaction forces were calculated with a 2 kg weight in the hand. RESULTS: In general, the maximal shoulder muscle force and joint reaction force values were in a similar range for both prosthesis models during all four motions. The maximal deltoid muscle forces in the model with the dual-bearing prosthesis were 18% lower for abduction and 3% higher for scaption compared to the natural shoulder. The maximal rotator cuff muscle forces in the model with the dual-bearing prosthesis were 36% lower for abduction and 1% higher for scaption compared to the natural shoulder. Although the maximal deltoid muscle forces in the model with the dual-bearing prosthesis in internal and external rotation were 52% and 64% higher, respectively, compared to the natural shoulder, the maximal rotator cuff muscle forces were 27% lower in both motions. CONCLUSION: The study shows that the dual-bearing shoulder prosthesis is a feasible option for patients with rotator cuff tear and has a strong potential to be used as secondary as well as primary joint replacement. The study also demonstrates that computer simulations can help to guide the continued optimization of this particular design concept for successful clinical outcomes.

Load Distribution in the Lumbar Spine During Modeled Compression Depends on Lordosis.

Excessive or incorrect loading of lumbar spinal structures is commonly assumed as one of the factors to accelerate degenerative processes, which may lead to lower back pain. Accordingly, the mechanics of the spine under medical conditions, such as scoliosis or spondylolisthesis, is well-investigated. Treatments via both conventional therapy and surgical methods alike aim at restoring a "healthy" (or at least pain-free) load distribution. Yet, surprisingly little is known about the inter-subject variability of load bearings within a "healthy" lumbar spine. Hence, we utilized computer tomography data from 28 trauma-room patients, whose lumbar spines showed no visible sign of degeneration, to construct simplified multi-body simulation models. The subject-specific geometries, measured by the corresponding lumbar lordosis (LL) between the endplates of vertebra L1 and the sacrum, served as ceteris paribus condition in a standardized forward dynamic compression procedure. Further, the influence of stimulating muscles from the M. multifidus group was assessed. For the range of available LL from 28 to 66°, changes in compressive and shear forces, bending moments, as well as facet joint forces between adjacent vertebrae were calculated. While compressive forces tended to decrease with increasing LL, facet forces were tendentiously increasing. Shear forces decreased between more cranial vertebrae and increased between more caudal ones, while bending moments remained constant. Our results suggest that there exist significant, LL-dependent variations in the loading of "healthy" spinal structures, which should be considered when striving for individually appropriate therapeutic measures.

Sensitivity of musculoskeletal model-based lumbar spinal loading estimates to type of kinematic input and passive stiffness properties.

The study investigated the potential for obtaining more accurate spine joint reaction force (JRF) estimates from musculoskeletal models by incorporating dynamic stereo X-ray imaging (DSX)-based in vivo lumbar vertebral rotational and translational kinematics compared to generic, rhythm (RHY)-based kinematics, while also observing the influence of accompanying inputs: intervertebral segment stiffness and neutral state. A full-body OpenSim® musculoskeletal model, constructed by combining existing lower- and upper-body models, was driven based on one volunteer's (female; age 25; 60.8 kg; 176 cm) anthropometrics and kinematics from a series of upright standing and straight-legged dynamic lifting tasks. The lumbar spine portion was modified in a step-wise manner to observe effects of: (1) RHY vs. DSX lumbar kinematics; (2) No disc (bushing) stiffness (NBS); generic, linear bushing stiffness (LBS); subject-specific nonlinear bushing stiffness (NLBS); (3) Upright standing (UP) vs. Supine (SUP) neutral state; (4) Weight lifted: 4.5 kg vs. 13.6 kg. L4L5 JRF from 24 model variations based on combinations of aforementioned parameters were compared. Rhythm-based kinematics without translational components tends to over-predict JRF (31% and 39% for compression and shear, respectively) compared to DSX-based kinematics. Additionally, differences due to accompanying passive stiffness and neutral state choice combinations were even larger (>50%), indicating heightened demand on the quality of these accompanying inputs. The study not only highlights model sensitivity to choices made regarding the three primary inputs-kinematics, passive stiffness and neutral state- separately, but also how interactions between these choices can result in significant variability in joint loading estimates.

In vivo changes in adjacent segment kinematics after lumbar decompression and fusion.

The pathogenesis of lumbar adjacent segment disease is thought to be secondary to altered biomechanics resulting from fusion. Direct in vivo evidence for altered biomechanics following lumbar fusion is lacking. This study's aim was to describe in vivo kinematics of the superior adjacent segment relative to the fused segment before and after lumbar fusion. This study analyzed seven patients with symptomatic lumbar degenerative spondylolisthesis (5 M, 2F; age 65 ± 5.1 years) using a biplane radiographic imaging system. Each subject performed two to three trials of continuous flexion of their torso according to established protocols. Synchronized biplane radiographs were acquired at 20 images per second one month before and six months after single-level fusion at L4-L5 or L5-S1, or two-level fusion at L3-L5 or L4-S1. A previously validated volumetric model-based tracking process was used to track the position and orientation of vertebrae in the radiographic images. Intervertebral flexion/extension and AP translation (slip) at the superior adjacent segment were calculated over the entire dynamic flexion activity. Skin-mounted surface markers were tracked using conventional motion analysis and used to determine torso flexion. Change in adjacent segment kinematics after fusion was determined at corresponding angles of dynamic torso flexion. Changes in adjacent segment motion varied across patients, however, all patients maintained or increased the amount of adjacent segment slip or intervertebral flexion/extension. No patients demonstrated both decreased adjacent segment slip and decreased rotation. This study suggests that short-term changes in kinematics at the superior adjacent segment after lumbar fusion appear to be patient-specific.

A Dynamic Radiographic Imaging Study of Lumbar Intervertebral Disc Morphometry and Deformation In Vivo.

Intervertebral discs are important structural components of the spine but also are significant sources of morbidity, especially for the "low back" lumbar region. Mechanical damage to, or degeneration of, the lumbar discs can diminish their structural integrity and elicit debilitating low back pain. Advancement of reparative or regenerative means to treat damaged or degenerated discs is hindered by a lack of basic understanding of the disc load-deformation characteristics in vivo. The current study presents an in vivo analysis of the morphometry and deformation of lumbar (L2-S1) intervertebral discs in 10 healthy participants while performing a common lifting act, using novel dynamic radiographic imaging of the lumbar vertebral body motion. Data analyses show uniquely different (p < 0.05) characteristics in morphometry, normal and shear strain patterns of the L5S1 discs, while the rest of lumbar discs exhibit great similarity. In particular shear strains in L2-L5 discs exhibited stronger linear correlations (R2 ≥ 0.80) between strain changes and amount of lumbar flexion-extension motion compared to L5S1 (R2 ≤ 0.5). The study therefore advances the state of knowledge on in vivo mechanical responses of the lumbar intervertebral discs during functional tasks.

Loading of the lumbar spine during backpack carriage.

Backpack carriage is significantly associated with a higher prevalence of low back pain. Elevated compression and shear forces in the lumbar intervertebral discs are known risk factors. A novel method of calculating the loads in the lumbar spine during backpack carriage is presented by combining physical and numerical modelling. The results revealed that to predict realistic lumbar compression forces, subject-specific lumbar curvature data were not necessary for loads up to 40 kg. In contrast, regarding shear forces, using subject-specific lumbar curvature data from upright MRI measurements as input for the rigid body model significantly altered lumbar joint force estimates.

Dependence of anisotropy of human lumbar vertebral trabecular bone on quantitative computed tomography-based apparent density.

Most studies investigating human lumbar vertebral trabecular bone (HVTB) mechanical property-density relationships have presented results for the superior-inferior (SI), or "on-axis" direction. Equivalent, directly measured data from mechanical testing in the transverse (TR) direction are sparse and quantitative computed tomography (QCT) density-dependent variations in the anisotropy ratio of HVTB have not been adequately studied. The current study aimed to investigate the dependence of HVTB mechanical anisotropy ratio on QCT density by quantifying the empirical relationships between QCT-based apparent density of HVTB and its apparent compressive mechanical properties--elastic modulus (E(app)), yield strength (σ(y)), and yield strain (ε(y))--in the SI and TR directions for future clinical QCT-based continuum finite element modeling of HVTB. A total of 51 cylindrical cores (33 axial and 18 transverse) were extracted from four L1 human lumbar cadaveric vertebrae. Intact vertebrae were scanned in a clinical resolution computed tomography (CT) scanner prior to specimen extraction to obtain QCT density, ρ(CT). Additionally, physically measured apparent density, computed as ash weight over wet, bulk volume, ρ(app), showed significant correlation with ρ(CT) [ρ(CT) = 1.0568 × ρ(app), r = 0.86]. Specimens were compression tested at room temperature using the Zetos bone loading and bioreactor system. Apparent elastic modulus (E(app)) and yield strength (σ(y)) were linearly related to the ρ(CT) in the axial direction [E(SI) = 1493.8 × (ρ(CT)), r = 0.77, p < 0.01; σ(Y,SI) = 6.9 × (ρ(CT)) − 0.13, r = 0.76, p < 0.01] while a power-law relation provided the best fit in the transverse direction [E(TR) = 3349.1 × (ρ(CT))(1.94), r = 0.89, p < 0.01; σ(Y,TR) = 18.81 × (ρ(CT))(1.83), r = 0.83, p < 0.01]. No significant correlation was found between ε(y) and ρ(CT) in either direction. E(app) and σ(y) in the axial direction were larger compared to the transverse direction by a factor of 3.2 and 2.3, respectively, on average. Furthermore, the degree of anisotropy decreased with increasing density. Comparatively, ε(y) exhibited only a mild, but statistically significant anisotropy: transverse strains were larger than those in the axial direction by 30%, on average. Ability to map apparent mechanical properties in the transverse direction, in addition to the axial direction, from CT-based densitometric measures allows incorporation of transverse properties in finite element models based on clinical CT data, partially offsetting the inability of continuum models to accurately represent trabecular architectural variations.

Subject-specific finite element modeling of the tibiofemoral joint based on CT, magnetic resonance imaging and dynamic stereo-radiography data in vivo.

In this paper, we present a new methodology for subject-specific finite element modeling of the tibiofemoral joint based on in vivo computed tomography (CT), magnetic resonance imaging (MRI), and dynamic stereo-radiography (DSX) data. We implemented and compared two techniques to incorporate in vivo skeletal kinematics as boundary conditions: one used MRI-measured tibiofemoral kinematics in a nonweight-bearing supine position and allowed five degrees of freedom (excluding flexion-extension) at the joint in response to an axially applied force; the other used DSX-measured tibiofemoral kinematics in a weight-bearing standing position and permitted only axial translation in response to the same force. Verification and comparison of the model predictions employed data from a meniscus transplantation study subject with a meniscectomized and an intact knee. The model-predicted cartilage-cartilage contact areas were examined against "benchmarks" from a novel in situ contact area analysis (ISCAA) in which the intersection volume between nondeformed femoral and tibial cartilage was characterized to determine the contact. The results showed that the DSX-based model predicted contact areas in close alignment with the benchmarks, and outperformed the MRI-based model: the contact centroid predicted by the former was on average 85% closer to the benchmark location. The DSX-based FE model predictions also indicated that the (lateral) meniscectomy increased the contact area in the lateral compartment and increased the maximum contact pressure and maximum compressive stress in both compartments. We discuss the importance of accurate, task-specific skeletal kinematics in subject-specific FE modeling, along with the effects of simplifying assumptions and limitations.

Capturing three-dimensional in vivo lumbar intervertebral joint kinematics using dynamic stereo-X-ray imaging.

Availability of accurate three-dimensional (3D) kinematics of lumbar vertebrae is necessary to understand normal and pathological biomechanics of the lumbar spine. Due to the technical challenges of imaging the lumbar spine motion in vivo, it has been difficult to obtain comprehensive, 3D lumbar kinematics during dynamic functional tasks. The present study demonstrates a recently developed technique to acquire true 3D lumbar vertebral kinematics, in vivo, during a functional load-lifting task. The technique uses a high-speed dynamic stereo-radiography (DSX) system coupled with a volumetric model-based bone tracking procedure. Eight asymptomatic male participants performed weight-lifting tasks, while dynamic X-ray images of their lumbar spines were acquired at 30 fps. A custom-designed radiation attenuator reduced the radiation white-out effect and enhanced the image quality. High resolution CT scans of participants' lumbar spines were obtained to create 3D bone models, which were used to track the X-ray images via a volumetric bone tracking procedure. Continuous 3D intervertebral kinematics from the second lumbar vertebra (L2) to the sacrum (S1) were derived. Results revealed motions occurring simultaneously in all the segments. Differences in contributions to overall lumbar motion from individual segments, particularly L2-L3, L3-L4, and L4-L5, were not statistically significant. However, a reduced contribution from the L5-S1 segment was observed. Segmental extension was nominally linear in the middle range (20%-80%) of motion during the lifting task, but exhibited nonlinear behavior at the beginning and end of the motion. L5-S1 extension exhibited the greatest nonlinearity and variability across participants. Substantial AP translations occurred in all segments (5.0 ± 0.3 mm) and exhibited more scatter and deviation from a nominally linear path compared to segmental extension. Maximum out-of-plane rotations (<1.91 deg) and translations (<0.94 mm) were small compared to the dominant motion in the sagittal plane. The demonstrated success in capturing continuous 3D in vivo lumbar intervertebral kinematics during functional tasks affords the possibility to create a baseline data set for evaluating the lumbar spinal function. The technique can be used to address the gaps in knowledge of lumbar kinematics, to improve the accuracy of the kinematic input into biomechanical models, and to support development of new disk replacement designs more closely replicating the natural lumbar biomechanics.

A new bone surrogate model for testing interbody device subsidence.

STUDY DESIGN: An in vitro biomechanical study investigating interbody device subsidence measures in synthetic vertebrae, polyurethane foam blocks, and human cadaveric vertebrae. OBJECTIVE: To compare subsidence measures of bone surrogates with human vertebrae for interbody devices varying in size/placement. SUMMARY OF BACKGROUND DATA: Bone surrogates are alternatives when human cadaveric vertebrae are unavailable. Synthetic vertebrae modeling cortices, endplates, and cancellous bone have been developed as an alternative to polyurethane foam blocks for testing interbody device subsidence. METHODS: Indentors placed on the endplates of synthetic vertebrae, foam blocks, and human vertebrae were subjected to uniaxial compression. Subsidence, measured with custom-made extensometers, was evaluated for an indentor seated either centrally or peripherally on the endplate. Failure force and indentation stiffness were determined from force-displacement curves. RESULTS: Subsidence measures in human vertebrae varied with indentor placement: failure forces were higher and indentors subsided less with peripheral placement. Subsidence measures in foam blocks were insensitive to indentor size/placement; they were similar to human vertebrae for centrally placed but not for peripherally placed indentors. Although subsidence measures in synthetic vertebrae were sensitive to indentor size/placement, failure force and indentation stiffness were overestimated, and subsidence underestimated, for both centrally placed and peripherally placed indentors. CONCLUSION: The synthetic endplate correctly represented the human endplate geometry, and thus, failure force, stiffness, and subsidence in synthetic vertebrae were sensitive to indentor size/placement. However, the endplate was overly strong and thus synthetic vertebrae did not accurately model indentor subsidence in human cadaveric vertebrae. Foam blocks captured subsidence measures more accurately than synthetic vertebrae for centrally placed indentors, but because of their uniform density were not sufficiently robust to capture changes generated from different indentor sizes/placements. The current bone surrogates are not accurate enough in terms of material property distribution to completely model subsidence in human cadaveric vertebrae.

Recovery of bone strength in young pigs from an induced short-term dietary calcium deficit followed by a calcium replete diet.

This study investigated whether the deficits in bone strength of pre-pubertal pigs, induced by short-term deficits in dietary calcium can be recovered if followed by a calcium-fortified diet. Young pigs were divided into two groups based on diet: a marginal Ca diet (70% of established Ca requirements) or an excess Ca diet (150% of established Ca requirements) for 4 weeks. Each group was then randomly sub-divided into two groups and fed diets with either marginal or excess dietary Ca for 6 weeks in a cross-over design, resulting in four treatment groups: H150-H150, H150-L70, L70-H150, and L70-L70. Animals were DXA scanned at 2-week intervals during the 10-week period to obtain whole body bone mineral content (BMC) and density (BMD). After animals were euthanized, right femurs were collected for this study. Traits such as bone mineral density, mass, volume, area moment of inertia (MI) and the section modulus (SM) were computed from computed tomography (CT) data and failure load was measured from four-point bending tests. DXA results showed significant reduction in BMC (61.6%) and BMD (37.5%) in the (L70-L70) group compared to the (H150-H150) group. DXA results additionally showed that deficiencies induced by the 4-week marginal Ca diet in the (L70-H150) group were not recovered with a subsequent excess Ca diet. While mechanical test results also showed significant reduction (75%) in strength in the L70-L70 group, compared to the H150-H150 group, they revealed no differences between the failure loads of the (L70-H150) group and the (H150-H150) group. Similar results were also found for bone mineral mass and volume, indicating that recovery from a short-term dietary Ca deficiency is possible at the pre-pubertal stage. Furthermore, bone mineral content and bone volume calculated from CT data correlated highly with failure load (R(2)=0.78 and 0.84, respectively), while density, MI and SM only showed weak-to-moderate correlations (R(2)=0.40-0.56), implying that bone mineral mass and volume calculated from CT data are good non-invasive surrogates for strength of growing bones.