Subsidence of Spinal Fusion Cages: A Systematic Review.

BACKGROUND: Although many research studies investigating subsidence of intervertebral fusion cages have been published, to our knowledge, no study has comprehensively compared cage subsidence among all lumbar intervertebral fusion (LIF) techniques. This study aimed to review the literature reporting evidence of cage subsidence linked to LIF. The amount of subsidence was compared and associated with the procedures and corresponding implants used, and the effect of cage subsidence on clinical outcomes was investigated. METHODS: For this systematic review, the MEDLINE and PubMed databases were used to identify relevant studies. Search terms included lumbar, lumbar vertebrae, lumbar spine, cage, spinal fusion, prosthesis, prosthesis implantation, implantation, implants, interbody, spacer, and subsidence. Studies included in this review were those having more than 10 patients and reporting the amount of subsidence observed using computed tomography or x-ray imaging after surgery and at follow-up visits after a minimum of 6 weeks postsurgery. Data and scale definitions related to subsidence were extracted from articles for comparison of subsidence prevalence between the 5 LIF surgical procedures. RESULTS: Forty articles were identified for inclusion. The review included data from 390 anterior lumbar intervertebral fusions (ALIFs), 2130 lateral lumbar intervertebral fusions (LLIFs), 560 posterior lumbar intervertebral fusions (PLIFs), 245 oblique lumbar intervertebral fusions (OLIFs), and 1634 transverse lumbar intervertebral fusions (TLIFs) for a total of 4959 patients who underwent LIF surgery. The minimum and maximum percentages of the number of patients having subsidence for each procedure in the included studies were as follows: ALIF stand-alone, 6% and 23.1%; LLIF stand-alone, 8.7% and 39.6%; LLIF with posterior fixation, 3.3% and 20.7%; OLIF with posterior fixation, 4.4% and 36.9%; PLIF with posterior fixation, 7.4% and 31.8%; and TLIF, 0.0% and 51.2%. CONCLUSIONS: The number of patients experiencing subsidence varied between studies within each fusion procedure. Our findings indicate that all 5 surgical methods are at risk of subsidence. Overall, ALIF without posterior fixation resulted in the lowest reported subsidence occurrence among the 5 surgical approaches. There is conflicting evidence on the association between subsidence and negative clinical outcomes. CLINICAL RELEVANCE: This review defines and compares subsidence incidence between all LIF procedures and investigates the risk of symptomatic clinical outcomes.

Intracranial Displacement Measurements Within Targeted Anatomical Regions of a Postmortem Human Surrogate Brain Subjected to Impact.

The dynamic response of the human brain subjected to impulsive loading conditions is of fundamental importance to the understanding of traumatic brain injuries. Due to the complexity of such measurements, the existing experimental datasets available to researchers are sparse. However, these measurements are used extensively in the validation of complex finite element models used in the design of protective equipment and the development of injury mitigation strategies. The primary objective of this study was to develop a comprehensive methodology to measure displacement in specific anatomical regions of the brain. A state-of-the-art high-speed cineradiography system was used to capture brain motion in post-mortem human surrogate specimens at a rate of 7500 fps. This paper describes the methodology used to capture these data and presents measurements from these tests. Two-dimensional displacement fields are presented and analyzed based on anatomical regions of the brain. These data demonstrated a multi-modal displacement response in several regions of the brain. The full response of the brain consisted of an elastic superposition of a series of bulk rotations of the brain about its centre of gravity. The displacement field could be linked directly to specific anatomical regions. The methods presented mark an improvement in temporal and spatial resolution of data collection, which has implications for our developing understanding of brain trauma.

A Parametric Analysis of Embedded Tissue Marker Properties and Their Effect on the Accuracy of Displacement Measurements.

Datasets obtained from cadaveric experimentation are broadly used in validating finite element models of head injury. Due to the complexity of such measurements in soft tissues, experimentalists have relied on tissue-embedded radiographic or sonomicrometry tracking markers to resolve tissue motion caused by impulsive loads. Dynamic coupling of markers with the surrounding tissue has been a previous concern, yet a thorough sensitivity investigation of marker influences on tissue deformation has not been broadly discussed. Technological improvements to measurement precision have bolstered confidence in acquired data; however, precision is often conflated with accuracy; the inclusion of markers in the tissue may alter its natural response, resulting in a loss of accuracy associated with an altered displacement field. To gain an understanding of how marker properties may influence the measured response to impact, we prepared a set of nine marker designs using a Taguchi L9 array to investigate marker design choice sensitivity. Each of these designs was cast into a block of tissue simulant and subjected to repeated drop tests. Vertical displacement was measured and compared to the response of the neat material, which contained massless tracking markers. Medium density and medium stiffness markers yielded the least deviation from the neat material response. The results provide some design guidelines indicating the importance of maintaining marker matrix density ratio below 1.75 and marker stiffness below 1.0 MPa. These properties may minimize marker interference in tissue deformation. Overall, embedded marker properties must be considered when measuring the dynamic response of tissue.

Impact-Induced Cortical Strain Concentrations at the Sulcal Base and Its Implications for Mild Traumatic Brain Injury.

This study investigated impact-induced strain fields within brain tissue surrogates having different cortical gyrification. Two elastomeric surrogates, one representative of a lissencephalic brain and the other of a gyrencephalic brain, were drop impacted in unison at four different heights and in two different orientations. Each surrogate contained a radiopaque speckle pattern that was used to calculate strain fields. Two different approaches, digital image correlation (DIC) and a particle tracking method, enabled comparisons of full-field and localized strain responses. The DIC results demonstrated increased localized deviations from the mean strain field in the surrogate with a gyrified cortex. Particle tracking algorithms, defining four-node quadrilateral elements, were used to investigate the differences in the strain response of three regions: the base of a sulcus, the adjacent gyrus, and the internal capsule of the surrogates. The results demonstrated that the strains in the cortex were concentrated at the sulcal base. This mechanical mechanism of increased strain is consistent with neurodegenerative markers observed in postmortem analyses, suggesting a potential mechanism of local damage due to strain amplification at the sulcal bases in gyrencephalic brains. This strain amplification mechanism may be responsible for cumulative neurodegeneration from repeated subconcussive impacts. The observed results suggest that lissencephalic animal models, such as rodents, would not have the same modes of injury present in a gyrencephalic brain, such as that of a human. As such, a shift toward representative mild traumatic brain injury animal models having gyrencephalic cortical structures should be strongly considered.

Previous Damage Accumulation Can Influence Femoral Fracture Strength: A Finite Element Study.

To manage osteoporotic hip fracture risk, it is necessary to understand failure mechanisms of bone at both the material and organ level. The structural response of bone is dependent on load history. Repeated loading causes progressive microstructural cracking, resulting in reduced apparent-level stiffness and, if damage is significant, reductions to peak load bearing capability. However, the effect of previous damage accumulation has not been well explored at the organ level. It was hypothesized that femoral fracture load and fracture pattern may be sensitive to damage accumulation from previous loading events. Six cadaveric specimens were used to develop patient specific finite element (FE) models from quantitative tomographic (qCT) scans. Material properties were assigned from qCT intensity at each element location, and damage evolution was predicted using a previously validated quasi-brittle FE model. Three scenarios were investigated: stumble followed by another stumble (S-S), fall followed by another fall (F-F), and stumble followed by a fall (S-F). Fracture load and pattern were compared to FE predictions for a single stumble (S) or single fall (F) loading event. Most specimens were resilient to accumulated damage, showing little (<5%) change in fracture load from the multiple-load scenarios (S-S, F-F, and S-F) compared to an equivalent single load scenario (S or F). Only one specimen demonstrated moderate (5-15%) reductions in strength from all three multiple-load scenarios. However, two specimens experienced moderate (20-30%) increase in fracture load in some load cases. In these cases, initial damage caused the load to be more evenly distributed upon subsequent loading events. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2197-2203, 2019.

Higher patient activity level and subchondral stiffening in asymptomatic cam femoroacetabular impingement subjects.

A cam deformity is proposed as a cause of idiopathic osteoarthritis. Increased subchondral bone mineral density (BMD) is associated with this degenerative process of osteoarthritis, and the patient's activity level may contribute to it. Therefore, the correlation between activity level and subchondral BMD in subjects with cam deformity FAI was studied. In this study, 26 asymptomatic cam deformity subjects (Bump) were compared with 18 subjects with a normal alpha angle (Control). Anterosuperior subchondral femoral neck and acetabular rim BMD were measured using quantitative computed tomography. Activity level was determined using the UCLA activity score. The correlation between BMD and UCLA activity were analysed. The result was a significantly higher BMD for Bump subjects in almost all measured sections. The UCLA score of the Bump versus Control subjects were comparable (8.96 versus 8.77, P = 0.740). While the controls showed no correlation between UCLA and BMD, a positive correlation was found for the Bump subjects on several femoral and acetabular impingement locations. These results support the conclusion that mechanical loading causes subchondral stiffening at the anterosuperior head-neck junction of the femur and anterosuperior acetabular rim. The absence of a correlation between BMD versus UCLA in the Controls supports the hypothesis that activity level may serve as a predictor for higher subchondral BMD in a cam deformity hip joint.

Unravelling the hip pistol grip/cam deformity: Origins to joint degeneration.

This article reviews a body of work performed by the investigators over 9 years that has addressed the significance of cam morphology in the development of hip osteoarthritis (OA). Early hip joint degeneration is a common clinical presentation and preexisting abnormal joint morphology is a risk factor for its development. Interrogating Hill's criteria, we tested whether cam-type femoroacetabular impingement leads to hip OA. Strength of association was identified between cam morphology, reduced range-of-movement, hip pain, and cartilage degeneration. By studying a pediatric population, we were able to characterize the temporality between cam morphology (occurring 1st) and joint degeneration. Using in silico (finite element) and in vivo (imaging biomarkers) studies, we demonstrated the biological plausibility of how a cam deformity can lead to joint degeneration. Furthermore, we were able to show a biological gradient between degree of cam deformity and extent of articular damage. However, not all patients develop joint degeneration and we were able to characterize which factors contribute to this (specificity). Lastly, we were able to show that by removing the cam morphology, one could positively influence the degenerative process (experiment). The findings of this body of work show consistency and coherence with the literature. Furthermore, they illustrate how cam morphology can lead to early joint degeneration analogous to SCFE, dysplasia, and joint mal-reduction post-injury. The findings of this study open new avenues on the association between cam morphology and OA including recommendations for the study, screening, follow-up, and assessment (patient-specific) of individuals with cam morphology in order to prevent early joint degeneration. Statement of significance: By satisfying Hill's criteria, one can deduct that in some individuals, cam morphology is a cause of OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3125-3135, 2018.

Femoral fracture load and fracture pattern is accurately predicted using a gradient-enhanced quasi-brittle finite element model.

Nonlinear finite element (FE) modeling can be a powerful tool for studying femoral fracture. However, there remains little consensus in the literature regarding the choice of material model and failure criterion. Quasi-brittle models recently have been used with some success, but spurious mesh sensitivity remains a concern. The purpose of this study was to implement and validate a new model using a custom finite element designed to mitigate mesh sensitivity problems. Six specimen-specific FE models of the proximal femur were generated from quantitative tomographic (qCT) scans of cadaveric specimens. Material properties were assigned a-priori based on average qCT intensities at element locations. Specimens were experimentally tested to failure in a stumbling load configuration, and the results were compared to FE model predictions. There was a strong linear relationship between FE predicted and experimentally measured fracture load (R2 = 0.79), and error was less than 14% over all cases. In all six specimens, surface damage was observed at sites predicted by the FE model. Comparison of qCT scans before and after experimental failure showed damage to underlying trabecular bone, also consistent with FE predictions. In summary, the model accurately predicted fracture load and pattern, and may be a powerful tool in future studies.

Validation of an alignment method using motion tracking system for in-vitro orientation of cadaveric hip joints with reduced set of anatomical landmarks.

Accurate in-vitro orientation of cadaveric hip joints is challenging due to limited available anatomical landmarks. Published hip joint in-vitro investigations commonly lack details on methods used to achieve reported orientations and the accuracy with which the desired orientation has been achieved. The aim of this study was to develop an accurate method for orienting hip joints with limited anatomical landmarks for in-vitro investigations, and to compare this method against orientation using guiding axes and by visual approximation. The proposed orientation method resulted in orientation angles achieved to within one degree (SD ±â€¯0.58°). For most specimens, orientation using physical tools resulted in errors of ±8° and ±12° in at least one of three orientation angles used to place the femur and pelvis in neutral orientation, respectively. Precision was also worse, with SDs ranging from ±1° to ±5° for orientation angles of femoral specimens and SDs ranging from ±1° to ±8° for pelvic specimens. The error in the orientation angles was worse for orientation by visual approximation and the range of SDs were greater for both the femur and pelvis. Finite element modeling was used to assess the effects of observed orientation errors, on prediction of fracture load. In most cases, the largest error in fracture load among all trials exceeded 30%, relative to a femur oriented without any error in the orientation angles.

Surgical Correction of Cam Deformity in Association with Femoroacetabular Impingement and Its Impact on the Degenerative Process within the Hip Joint.

BACKGROUND: Cam morphology in association with femoroacetabular impingement (FAI) is a recognized cause of hip pain and cartilage damage and proposed as a leading cause of arthritis. The purpose of this study was to analyze the functional and biomechanical effects of the surgical correction of the cam deformity on the degenerative process associated with FAI. METHODS: Ten male patients with a mean age of 34.3 years (range, 23.1 to 46.5 years) and a mean body mass index (and standard deviation) of 26.66 ± 4.79 kg/m underwent corrective surgery for cam deformity in association with FAI. Each patient underwent a computed tomography (CT) scan to assess acetabular bone mineral density (BMD), high-resolution T1ρ magnetic resonance imaging (MRI) of the hips to assess proteoglycan content, and squatting motion analysis as well as completed self-administered functional questionnaires (Hip disability and Osteoarthritis Outcome Score [HOOS]) both preoperatively and 2 years postoperatively. RESULTS: At a mean follow-up of 24.5 months, improvements in functional scores and squat performance were seen. Regarding the zone of impingement in the anterosuperior quadrant of the acetabular rim, the mean change in BMD at the time of follow-up was -31.8 mg/cc (95% confidence interval [CI], -11 to -53 mg/cc) (p = 0.008), representing a 5% decrease in BMD. The anterosuperior quadrant also demonstrated a significant decrease in T1ρ values, reflecting a stabilization of the cartilage degeneration. Significant correlations were noted between changes in clinical functional scores and changes in T1ρ values (r = -0.86; p = 0.003) as well as between the BMD and maximum vertical force (r = 0.878; p = 0.021). CONCLUSIONS: Surgical correction of a cam deformity in patients with symptomatic FAI not only improved clinical function but was also associated with decreases in T1ρ values and BMD. These findings are the first, to our knowledge, to show that alteration of the hip biomechanics through surgical intervention improves the overall health of the hip joint. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Properties of the cartilage layer from the cam-type hip impingement deformity.

Femoro-acetabular impingement (FAI) is associated with significant acetabular cartilage damage and degenerative arthritis. To understand the contact stress and thus biomechanical mechanisms that may contribute to degeneration, the material behaviour of the cartilage layer is required. The objective of this study is to determine the fibril-reinforced poroelastic properties and composition of cartilage from cam deformities and to compare to those of normal cartilage. Patients undergoing surgical treatment of a symptomatic cam FAI deformity were recruited from the clinical practice of one of the authors. Osteochondral specimens were retrieved from the deformity during surgery using a trephine. Control specimens were retrieved from the anterior femoral head bearing surface during autopsy procedures. Indentation stress-relaxation tests were performed to determine the modulus (ES), Poisson's ratio (ν) and permeability (k0) of the poroelastic component, and the strain-independent (E0) and -dependent (Eε) moduli of the fibril-reinforcement using finite element analysis and optimization. Safranin-O staining was used to quantify proteoglycan content. ES and ν were 71% and 37% lower, respectively, in Cam specimens compared to controls, and k0 was approximately triple that of Control specimens (p<0.05). No significant differences were seen in the fibrillar components, E0 and Eε. Proteoglycan content was substantially depleted in Cam specimens, and was correlated with ES, ν and k0. This study showed that cartilage from the cam deformity exhibits severe degeneration in terms of the mechanical behaviour and composition changes, and is consistent with osteoarthritis. This further supports the hypothesis that FAI is a cause of hip osteoarthritis.

Influence of ingrowth regions on bone remodelling around a cementless hip resurfacing femoral implant.

Hip resurfacing arthroplasty is an alternative to traditional hip replacement that can conserve proximal bone stock and has gained popularity but bone resorption may limit implant survival and remains a clinical concern. The goal of this study was to analyze bone remodelling patterns around an uncemented resurfacing implant and the influence of ingrowth regions on resorption. A computed tomography-derived finite element model of a proximal femur with a virtually implanted resurfacing component was simulated under peak walking loads. Bone ingrowth was simulated by six interface conditions: fully bonded; fully friction; bonded cap with friction stem; a small bonded region at the stem-cup intersection with the remaining surface friction; fully frictional, except for a bonded band along the distal end of the cap and superior half of the cap bonded with the rest frictional. Interface condition had a large influence on remodelling patterns. Bone resorption was minimized when no ingrowth occurred at the bone-implant interface. Bonding only the superior half of the cap increased bone resorption slightly but allowed for a large ingrowth region to improve secondary stability.

Stress distribution and consolidation in cartilage constituents is influenced by cyclic loading and osteoarthritic degeneration.

The understanding of load support mechanisms in cartilage has evolved with computational models that better mimic the tissue ultrastructure. Fibril-reinforced poroelastic models can reproduce cartilage behaviour in a variety of test conditions and can be used to model tissue anisotropy as well as assess stress and pressure partitioning to the tissue constituents. The goal of this study was to examine the stress distribution in the fibrillar and non-fibrillar solid phase and pressure in the fluid phase of cartilage in axisymmetric models of a healthy and osteoarthritic hip joint. Material properties, based on values from the literature, were assigned to the fibrillar and poroelastic components of cartilage and cancellous and subchondral compact bone regions. A cyclic load representing walking was applied for 25 cycles. Contact stresses in the fibrillar and non-fibrillar solid phase supported less than 1% of the contact force and increased only minimally with load cycles. Simulated proteoglycan depletion increased stresses in the radial and tangential collagen fibrils, whereas fibrillation of the tangential fibrils resulted in increased compressive stress in the non-fibrillar component and tensile stress in the radial fibrils. However neither had an effect on fluid pressure. Subchondral sclerosis was found to have the largest effect, resulting in increased fluid pressure, non-fibrillar compressive stress, tangential fibril stress and greater cartilage consolidation. Subchondral bone stiffening may play an important role in the degenerative cascade and may adversely affect tissue repair and regeneration treatments.

Effect of boundary conditions, impact loading and hydraulic stiffening on femoral fracture strength.

Patient specific quantitative CT (QCT) imaging data together with the finite element (FE) method may provide an accurate prediction of a patient's femoral strength and fracture risk. Although numerous FE models investigating femoral fracture strength have been published, there is little consent on the effect of boundary conditions, dynamic loading and hydraulic strengthening due to intra-medullary pressure on the predicted fracture strength. We developed a QCT-derived FE model of a proximal femur that included node-specific modulus assigned based on the local bone density. The effect of three commonly used boundary conditions published in literature were investigated by comparing the resulting strain field due to an applied fracture load. The models were also augmented with viscoelastic material properties and subject to a realistic impact load profile to determine the effect of dynamic loads on the strain field. Finally, the effect of hydraulic strengthening was investigated by including node specific permeability and performing a coupled pore diffusion and stress analysis of the FE model. Results showed that all boundary conditions yield the same strain field patterns, but peak strains were 22% lower and fracture load was 18% higher when loaded at the greater trochanter than when loaded at the femoral head. Comparison of the dynamic models showed that material viscoelasticity was important, but inertial effects (vibration and shock) were not. Finally, pore pressure changes did not cause significant hydraulic strengthening of bone under fall impact loading.

In vivo evaluation of calcium polyphosphate for bone regeneration.

Current problems associated with bone allografts include risk of disease transmission, limited availability, and cost. Synthetic scaffolds have been proposed as substitute graft materials to address these issues. Calcium polyphosphate is a novel synthetic scaffold material that has shown good mechanical properties and biocompatibility. Here, we evaluated calcium polyphosphate in terms of its ability to support cell proliferation and differentiation in vivo. Calcium polyphosphate, morsellized cancellous bone, and hydroxyapatite/tricalcium phosphate particles were seeded with marrow stromal cells and implanted subcutaneously in the back of NOD/Scid mice. At 7, 14, and 28 days the samples were harvested and the proliferation characteristics and gene expression were analyzed. All tested graft materials had similar proliferation characteristics and gene expression. The subcutaneous environment had a stronger impact on the proliferation and differentiation of the cells than the scaffold material itself. However, it was shown that calcium polyphosphate is superior to hydroxyapatite/tricalcium phosphate and bone in its ability to support cell survival in vivo. The study confirmed that calcium polyphosphate has potential for replacing morsellized cancellous bone as a graft material for bone regeneration.

Mechanisms of stem subsidence in femoral impaction allografting.

Failure of the femoral component of total hip arthroplasty is often accompanied by bone loss that can pose a significant challenge to the orthopaedic surgeon. Femoral impaction allografting has attractive potential for restoring bone stock in deficient femurs. However, there have been reports of problematic postoperative stem subsidence with this procedure. Subsidence is highly variable among patients, and there is disagreement over the mechanisms that cause it. This article reviews the various mechanisms that can contribute to subsidence in femoral impaction allografting. Variables such as graft density, cement penetration profile, use of synthetic graft substitutes, or other graft additives are discussed, as well as their potential impact on subsidence. Finally, recommendations are made for future studies aiming to reduce the risk of excessive subsidence in femoral impaction allografting.

The effect of abductor muscle and anterior-posterior hip contact load simulation on the in-vitro primary stability of a cementless hip stem.

BACKGROUND: In-vitro mechanical tests are commonly performed to assess pre-clinically the effect of implant design on the stability of hip endoprostheses. There is no standard protocol for these tests, and the forces applied vary between studies. This study examines the effect of the abductor force with and without application of the anterior-posterior hip contact force in the in-vitro assessment of cementless hip implant stability. METHODS: Cementless stems (VerSys Fiber Metal) were implanted in twelve composite femurs which were divided into two groups: group 1 (N = 6) was loaded with the hip contact force only, whereas group 2 (N = 6) was additionally subjected to an abductor force. Both groups were subjected to the same cranial-caudal hip contact force component, 2.3 times body weight (BW) and each specimen was subjected to three levels of anterior-posterior hip contact load: 0, -0.1 to 0.3 BW (walking), and -0.1 to 0.6 BW (stair climbing). The implant migration and micromotion relative to the femur was measured using a custom-built system comprised of 6 LVDT sensors. RESULTS: Substantially higher implant motion was observed when the anterior-posterior force was 0.6BW compared to the lower anterior-posterior load levels, particularly distally and in retroversion. The abductor load had little effect on implant motion when simulating walking, but resulted in significantly less motion than the hip contact force alone when simulating stair climbing. CONCLUSIONS: The anterior-posterior component of the hip contact load has a significant effect on the axial motion of the stem relative to the bone. Inclusion of the abductor force had a stabilizing effect on the implant motion when simulating stair climbing.

Effect of bone graft substitute on marrow stromal cell proliferation and differentiation.

Marrow stromal cells (MSCs) are ideally suited for tissue engineered bone grafts since they have the potential to regenerate bone, but may also maintain the homeostasis of the repaired tissue through their ability for self-renewal. An ideal bone graft substitute should support MSC self-renewal as well as differentiation to ensure complete bone defect regeneration and maintenance. The purpose of this investigation was to determine the effect of different substrate materials on MSC expansion and differentiation. Calcium polyphosphate (CPP), bone and hydroxyapatite/tricalcium phosphate (HA/TCP) were seeded with rat MSCs and maintained in culture conditions that promote cell expansion. At 0, 3, 7, 14, and 21 days cell numbers were determined by measuring their metabolic activity using a MTT assay and the frequency of cycling cells by 24 hr BrdU incorporation. Osteogenic, chondrogenic, and adipogenic marker expression in these cultures was measured by qRT-PCR. An initial drop in cell numbers was observed on all substrates. CPP and bone, but not HA/TCP supported an increase in proliferating cells at day 14 and 21. In addition, no upregulation of mature bone markers was observed in cells cultured on CPP and bone, which suggests that these substrates support the expansion of undifferentiated MSCs. In contrast, cell numbers on HA/TCP decreased with time and only rare BrdU positive cells were observed. This decrease in proliferation correlated with the down regulation of osteogenic progenitor markers and the substantial increase in mature osteocyte markers, indicating that HA/TCP favors MSC differentiation and maturation along the osteogenic lineage.

The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds.

Tissue engineering and stem cell therapy hold great potential of being able to fully restore, repair and replace damaged, diseased or lost tissues in the body. Biocompatible porous scaffolds are used for the delivery of cells to the regeneration sites. Marrow stromal cells (MSCs), also referred to as mesenchymal stem cells, are an attractive cell source for tissue engineering, due to the relative ease of isolation and the ability of in vitro expanded MSCs to generate multiple cell types, including osteoblasts, chondrocytes and adipocytes. This study utilized a novel technique called microwave vacuum drying to fabricate porous gelatin-alginate scaffolds for the delivery of MSCs and investigated the differential in vitro and in vivo responses of MSCs seeded on these scaffolds. Scaffold total porosity was found to decrease with increased cross-link density but the pore size and pore size distribution were not affected. Although highly porous, the scaffold had relatively small pores and limited interconnectivity. The porous gelatin-alginate scaffold demonstrated excellent biocompatibility with neovascularization on the surfaces and was bioresorbed completely in vivo, depending upon the cross-link density. MSCs were able to attach and proliferate at the same rate on the scaffolds, and the self-renewal potential of MSC cultures was similar during both in vitro culture and in vivo implantation. However, the subcutaneous microenvironment was found to suppress MSC differentiation along the osteogenic, chondrogenic and adipogenic lineages compared to in vitro conditions, highlighting the differential responses of MSCs cultured in vitro compared to implantation in vivo.

Effects of continuous and pulsatile PTH treatments on rat bone marrow stromal cells.

Bone marrow stromal cells (MSCs) differentiation and proliferation are controlled by numerous growth factors and hormones. Continuous parathyroid hormone (PTH) treatment has been shown to decrease osteoblast differentiation, whereas pulsatile PTH increases osteoblast differentiation. However, the effects of PTH treatments on MSCs have not been investigated. This study showed continuous PTH treatment in the presence of dexamethasone (DEX) promoted osteogenic differentiation of rat MSCs in vitro, as demonstrated by increased alkaline phosphatase (ALP) activity, number of ALP expressing cells, and up-regulation of PTH receptor-1, ALP, and osteocalcin mRNA expressions. In contrast, pulsatile PTH treatment was found to suppress osteogenesis of rat MSCs, possibly by promoting the maintenance of undifferentiated cells. Additionally, the observed effects of PTH were strongly dependent on the presence of DEX. MSC proliferation however was not influenced by PTH independent of treatment regimen and presence or absence of DEX. Furthermore, our work raised the possibility that PTH treatment may modulate stem/progenitor cell activity within MSC cultures.