Fabrication of Customizable and Reproducible 3D Chondrocyte-Laden Nanofibrous Architectures: Effect of Specific Fiber Alignments and Porosities on Chondrocyte Response under Cyclic Compression.

Electrospinning has been widely employed to fabricate complex extracellular matrix-like microenvironments for tissue engineering due to its ability to replicate structurally biomimetic micro- and nanotopographic cues. Nevertheless, these nanofibrous structures are typically either confined to bidimensional systems or confined to three-dimensional ones that are unable to provide controlled multiscale patterns. Thus, an electrospinning modality was used in this work to fabricate chondrocyte-laden nanofibrous scaffolds with highly customizable three-dimensional (3D) architectures in an automated manner, with the ultimate goal of recreating a suitable 3D scaffold for articular cartilage tissue engineering. Three distinct architectures were designed and fabricated by combining multiple nanofibrous and chondrocyte-laden hydrogel layers and tested in vitro in a compression bioreactor system. Results demonstrated that it was possible to precisely control the placement and alignment of electrospun polycaprolactone and gelatin nanofibers, generating three unique architectures with distinctive macroscale porosity, water absorption capacity, and mechanical properties. The architecture organized in a lattice-like fashion was highly porous with substantial pore interconnectivity, resulting in a high-water absorption capacity but a poor compression modulus and relatively weaker energy dissipation capacity. The donut-like 3D geometry was the densest, with lower swelling, but the highest compression modulus and improved energy dissipation ability. The third architecture combined a lattice and donut-like fibrous arrangement, exhibiting intermediary behavior in terms of porosity, water absorption, compression modulus, and energy dissipation capacity. The properties of the donut-like 3D architecture demonstrated great potential for articular cartilage tissue engineering, as it mimicked key topographic, chemical, and mechanical characteristics of chondrocytes' surrounding environment. In fact, the combination of these architectural features with a dynamically compressive mechanical stimulus triggered the best in vitro results in terms of viability and biosynthetic production.

Three-dimensional nanofibrous and porous scaffolds of poly(ε-caprolactone)-chitosan blends for musculoskeletal tissue engineering.

One of the established tissue engineering strategies relies on the fabrication of appropriate materials architectures (scaffolds) that mimic the extracellular matrix (ECM) and assist the regeneration of living tissues. Fibrous structures produced by electrospinning have been widely used as reliable ECM templates but their two-dimensional structure restricts, in part, cell infiltration and proliferation. A recent technique called thermally-induced self-agglomeration (TISA) allowed to alleviate this drawback by rearranging the 2D electrospun membranes into highly functional 3D porous-fibrous systems. Following this trend, the present research focused on preparing polycaprolactone/chitosan blends by electrospinning, to then convert them into 3D structures by TISA. By adding different amounts of chitosan, it was possible to accurately modulate the physicochemical properties of the obtained 3D nanofibrous scaffolds, leading to highly porous constructs with distinct morphologic and mechanical features. Viability and proliferation studies using adult human chondrocytes also revealed that the biocompatibility of the scaffolds was not impaired after 28 days of cell culture, highlighting their potential to be included into musculoskeletal tissue engineering applications, particularly cartilage repair.

Mechanical consequences at the tendon-bone interface of different medial row knotless configurations and lateral row tension in a simulated rotator cuff repair.

PURPOSE: Little is known about the direct influence of different technical options at the rotator cuff tendon-bone interface (TBI) and, more specifically, at the medial bearing row (MBR), regarding local contact force, area and pressure. We evaluated the mechanical repercussions of different medial row anchor configurations for that setting using different values of tension in the lateral row anchors. METHODS: Knotless transosseous equivalent (TOE) rotator cuff repairs with locked versus nonlocked medial anchors and single versus double-hole suture passage were tested in a synthetic rotator cuff mechanical model, using 2 different values of lateral row tension. Contact force, area, pressure, peak force and MBR force were compared at the simulated TBI using a pressure mapping sensor. RESULTS: When compared to locked anchors, medial row sliding configurations generate lower values for all the above-mentioned parameters. The use of double-hole suture passage in the medial cuff generated slightly higher values contact area regardless of lateral row tension. At higher lateral row tension values, lower values of the remaining parameters, including MBR force, were found when compared to single-hole suture passage. Lateral row anchor tension increase induced an increase of all parameters regardless of the medial row configuration and TBI contact force and MBR force were the most susceptible parameters, regardless of the medial row pattern. CONCLUSION: Medial row mechanism, suture configuration and lateral row tension interfere with the mechanical force, area and pressure at by TBI. Lateral row tension increase is a major influencer in those parameters. These results can help surgeons choose the right technique considering its mechanical effect at the TBI.

Is Graphene Shortening the Path toward Spinal Cord Regeneration?

Along with the development of the next generation of biomedical platforms, the inclusion of graphene-based materials (GBMs) into therapeutics for spinal cord injury (SCI) has potential to nourish topmost neuroprotective and neuroregenerative strategies for enhancing neural structural and physiological recovery. In the context of SCI, contemplated as one of the most convoluted challenges of modern medicine, this review first provides an overview of its characteristics and pathophysiological features. Then, the most relevant ongoing clinical trials targeting SCI, including pharmaceutical, robotics/neuromodulation, and scaffolding approaches, are introduced and discussed in sequence with the most important insights brought by GBMs into each particular topic. The current role of these nanomaterials on restoring the spinal cord microenvironment after injury is critically contextualized, while proposing future concepts and desirable outputs for graphene-based technologies aiming to reach clinical significance for SCI.

Tensile Strength Essay Comparing Three Different Platelet-Rich Fibrin Membranes (L-PRF, A-PRF, and A-PRF+): A Mechanical and Structural In Vitro Evaluation.

Predictable outcomes intended by the application of PRF (platelet-rich fibrin) derivative membranes have created a lack of consideration for their consistency and functional integrity. This study aimed to compare the mechanical properties through tensile strength and analyze the structural organization among the membranes produced by L-PRF (leukocyte platelet-rich fibrin), A-PRF (advanced platelet-rich fibrin), and A-PRF+ (advanced platelet-rich fibrin plus) (original protocols) that varied in centrifugation speed and time. L-PRF (n = 12), A-PRF (n = 19), and A-PRF+ (n = 13) membranes were submitted to a traction test, evaluating the maximum and average traction. For maximum traction, 0.0020, 0.0022, and 0.0010 N·mm−2 were obtained for A-PRF, A-PRF+, and L-PRF, respectively; regarding the average resistance to traction, 0.0012, 0.0015, and 0.006 N·mm−2 were obtained, respectively (A-PRF+ > A-PRF > L-PRF). For all groups studied, significant results were found. In the surface morphology observations through SEM, the L-PRF matrix showed a highly compact surface with thick fibers present within interfibrous areas with the apparent destruction of red blood cells and leukocytes. The A-PRF protocol showed a dense matrix composed of thin and elongated fibers that seemed to follow a preferential and orientated direction in which the platelets were well-adhered. Porosity was also evident with a large diameter of the interfibrous spaces whereas A-PRF+ was the most porous platelet concentrate with the greatest fiber abundance and cell preservation. Thus, this study concluded that A-PRF+ produced membranes with significant and higher maximum traction results, indicating a better viscoelastic strength when stretched by two opposing forces.

Bio-electrospraying assessment toward in situ chondrocyte-laden electrospun scaffold fabrication.

Electrospinning has been widely used to fabricate fibrous scaffolds for cartilage tissue engineering, but their small pores severely restrict cell infiltration, resulting in an uneven distribution of cells across the scaffold, particularly in three-dimensional designs. If bio-electrospraying is applied, direct chondrocyte incorporation into the fibers during electrospinning may be a solution. However, before this approach can be effectively employed, it is critical to identify whether chondrocytes are adversely affected. Several electrospraying operating settings were tested to determine their effect on the survival and function of an immortalized human chondrocyte cell line. These chondrocytes survived through an electric field formed by low needle-to-collector distances and low voltage. No differences in chondrocyte viability, morphology, gene expression, or proliferation were found. Preliminary data of the combination of electrospraying and polymer electrospinning disclosed that chondrocyte integration was feasible using an alternated approach. The overall increase in chondrocyte viability over time indicated that the embedded cells retained their proliferative capacity. Besides the cell line, primary chondrocytes were also electrosprayed under the previously optimized operational conditions, revealing the higher sensitivity degree of these cells. Still, their post-electrosprayed viability remained considerably high. The data reported here further suggest that bio-electrospraying under the optimal operational conditions might be a promising alternative to the existent cell seeding techniques, promoting not only cells safe delivery to the scaffold, but also the development of cellularized cartilage tissue constructs.

Biomimetic Graphene/Spongin Scaffolds for Improved Osteoblasts Bioactivity via Dynamic Mechanical Stimulation.

Biomimetics offers excellent prospects for design a novel generation of improved biomaterials. Here the controlled integration of graphene oxide (GO) derivatives with a 3D marine spongin (MS) network is explored to nanoengineer novel smart bio-based constructs for bone tissue engineering. The results point out that 3D MS surfaces can be homogeneously coated by layer-by-layer (LbL) assembly of oppositely charged polyethyleneimine (PEI) and GO. Notably, the GOPEI@MS bionanocomposites present a high structural and mechanical stability under compression tests in wet conditions (shape memory). Dynamic mechanically (2 h of sinusoidal compression cyclic interval (0.5 Hz, 0-10% strain)/14 d) stimulates GOPEI@MS seeded with osteoblast (MC3T3-E1), shows a significant improvement in bioactivity, with cell proliferation being two times higher than under static conditions. Besides, the dynamic assays show that GOPEI@MS bionanocomposites are able to act as mechanical stimulus-responsive scaffolds able to resemble physiological bone extracellular matrix (ECM) requirements by strongly triggering mineralization of the bone matrix. These results prove that the environment created by the system cell-GOPEI@MS is suitable for controlling the mechanisms regulating mechanical stimulation-induced cell proliferation for potential in vivo experimentation.

Multi-layered electrospinning and electrospraying approach: Effect of polymeric supplements on chondrocyte suspension.

Articular cartilage was expected to be one of the first tissues to be successfully engineered, but replicating the complex fibril architecture and the cellular distribution of the native cartilage has proven difficult. While electrospinning has been widely used to reproduce the depth-dependent fibre architecture in 3D scaffolds, the chondrocyte-controlled distribution remains an unsolved problem. To incorporate cells homogeneously through the depth of scaffolds, a combination of polymer electrospinning and cell seeding is necessary. A multi-layer approach alternating between polymer electrospinning with chondrocyte electrospraying can be a solution. Still, the success of this process is related to the survival rate of the electrosprayed chondrocytes embedded within the electrospun mesh. In this regard, the present study investigated the impact of the multi-layered process and the supplementation of the electrospray chondrocyte suspension with different concentrations of Gelatin and Alginate on the viability of electrosprayed chondrocytes embedded within a Polycaprolactone/Gelatin electrospun mesh and on the mechanical properties of the resulting meshes. The addition of Gelatin in the chondrocyte suspension did not increase significantly (p > 0.05) the percentage of viable electrosprayed chondrocytes (25%), while 3 wt% Alginate addition led to a significant (p < 0.05) increase in chondrocyte viability (50%) relative to the case without polymer supplement (15%). Furthermore, the addition of both polymer supplements increased the mechanical properties of the multi-layer construct. These findings imply that this multi-layered approach can be applied to cartilage TE allowing for automated chondrocyte integration during scaffolds creation.

Boosting in vitro cartilage tissue engineering through the fabrication of polycaprolactone-gelatin 3D scaffolds with specific depth-dependent fiber alignments and mechanical stimulation.

Due to the limited self-healing ability of natural cartilage, several tissue engineering strategies have been explored to develop functional replacements. Still, most of these approaches do not attempt to recreate in vitro the anisotropic organization of its extracellular matrix, which is essential for a suitable load-bearing function. In this work, different depth-dependent alignments of polycaprolactone-gelatin electrospun fibers were assembled into three-dimensional scaffold architectures to assess variations on chondrocyte response under static, unconfined compressed and perfused culture conditions. The in vitro results confirmed that not only the 3D scaffolds specific depth-dependent fiber alignments potentiated chondrocyte proliferation and migration towards the fibrous systems, but also the mechanical stimulation protocols applied were able to enhance significantly cell metabolic activity and extracellular matrix deposition, respectively.

Why are tapes better than wires in knotless rotator cuff repairs? An evaluation of force, pressure and contact area in a tendon bone unit mechanical model.

PURPOSE: Knotless repairs have demonstrated encouraging performance regarding retear rate reduction, but literature aiming at identifying the specific variables responsible for these results is scarce and conflictive. The purpose of this paper was to evaluate the effect of the material (tape or wire suture) and medial tendon passage (single or double passage) on the contact force, pressure and area at the tendon bone interface in order to identify the key factors responsible for this repairs´ success. METHODS: A specific knotless transosseous equivalent cuff repair was simulated using 2 tape or suture wire loaded medial anchors and 2 lateral anchors, with controlled lateral suture limb tension. The repair was performed in a previously validated sawbones® mechanical model. Testing analyzed force, pressure and area in a predetermined and constant size "repair box" using a Tekscan® sensor, as well as peak force and pressure, force applied by specific sutures and force variation along the repair box. RESULTS: Tapes generate lower contact force and pressure and double medial passage at the medial tendon is associated with higher contact area. Suture wires generate higher peak force and pressure on the repair and higher mean force in their tendon path and at the medial bearing row. Force values decrease from medial to lateral and from posterior to anterior independently of the material or medial passage. CONCLUSION: Contrary to most biomechanical literature, suture tape use lowers the pressure and force applied at the tendon bone junction, while higher number of suture passage points medially increases the area of contact. These findings may explain the superior clinical results obtained with the use uf suture tapes because its smaller compressive effect over the tendon may create a better perfusion environment healing while maintaining adequate biomechanical stability.

Tensile strength assay comparing the resistance between two different autologous platelet concentrates (leucocyte-platelet rich fibrin versus advanced-platelet rich fibrin): a pilot study.

BACKGROUND: Since the leucocyte-platelet rich fibrin (L-PRF) was published in 2001, many studies have been developed, analyzing its properties, and also verifying new possibilities to improve it. Thereby, it emerges the advanced-platelet rich fibrin (A-PRF) with a protocol that optimizes the properties obtained by the L-PRF. Nonetheless, there is a gap in the literature to landmark the evolutive process concerning the mechanical properties in specific the resistance to tensile strength which consequently may influence the time for membrane degradation. Thus, this study had the goal to compare the resistance to the traction of membranes produced with the original L-PRF and A-PRF protocols, being the first to this direct comparison. FINDINGS: The harvest of blood from a healthy single person, with no history of anticoagulant usage. We performed the protocols described in the literature, within a total of 13 membranes produced for each protocol (n = 26). Afterward, the membranes were prepared and submitted to a traction test assessing the maximal and the average traction achieved for each membrane. The data were analyzed statistically using the unpaired t test. Regarding average traction, A-PRF obtained a value of 0.0288 N mm-2 and L-PRF 0.0192 N mm-2 (p < 0.05 using unpaired t test). For maximal traction, A-PRF obtained 0.0752 N mm-2 and L-PRF 0.0425 N mm-2 (p < 0.05 using unpaired t test). CONCLUSION: With this study, it was possible to conclude that indeed A-PRF has a significative higher maximal traction score and higher average traction compared to L-PRF, indicating that it had a higher resistance when two opposing forces are applied.

3D Reduced Graphene Oxide Scaffolds with a Combinatorial Fibrous-Porous Architecture for Neural Tissue Engineering.

Graphene oxide (GO) assists a diverse set of promising routes to build bioactive neural microenvironments by easily interacting with other biomaterials to enhance their bulk features or, alternatively, self-assembling toward the construction of biocompatible systems with specific three-dimensional (3D) geometries. Herein, we first modulate both size and available oxygen groups in GO nanosheets to adjust the physicochemical and biological properties of polycaprolactone-gelatin electrospun nanofibrous systems. The results show that the incorporation of customized GO nanosheets modulates the properties of the nanofibers and, subsequently, markedly influences the viability of neural progenitor cell cultures. Interestingly, the partially reduced GO (rGO) nanosheets with larger dimensions trigger the best cell response, while the rGO nanosheets with smaller size provoke an accentuated decrease in the cytocompatibility of the resulting electrospun meshes. Then, the most auspicious nanofibers are synergistically accommodated onto the surface of 3D-rGO heterogeneous porous networks, giving rise to fibrous-porous combinatorial architectures suitable for enhancing adhesion and differentiation of neural cells. By varying the chemical composition of the nanofibers, it is possible to adapt their performance as physical crosslinkers for the rGO sheets, leading to the modulation of both pore size and structural/mechanical integrity of the scaffold. Importantly, the biocompatibility of the resultant fibrous-porous systems is not compromised after 14 days of cell culture, including standard differentiation patterns of neural progenitor cells. Overall, in light of these in vitro results, the reported scaffolding approach presents not only an indisputable capacity to support highly viable and interconnected neural circuits but also the potential to unlock novel strategies for neural tissue engineering applications.

Microfabrication of a biomimetic arcade-like electrospun scaffold for cartilage tissue engineering applications.

In recent years, the engineering of biomimetic cellular microenvironments has emerged as a top priority for regenerative medicine, being the in vitro recreation of the arcade-like cartilaginous tissue one of the most critical challenges due to the notorious absence of cost- and time-efficient microfabrication techniques capable of building 3D fibrous scaffolds with precise anisotropic properties. Taking this into account, we suggest a feasible and accurate methodology that uses a sequential adaptation of an electrospinning-electrospraying set up to construct a hierarchical system comprising both polycaprolactone (PCL) fibres and polyethylene glycol sacrificial microparticles. After porogen leaching, the bi-layered PCL scaffold was capable of presenting not only a depth-dependent fibre orientation similar to natural cartilage, but also mechanical features and porosity proficient to encourage an enhanced cell response. In fact, cell viability studies confirmed the biocompatibility of the scaffold and its ability to guarantee suitable cell adhesion, proliferation and migration throughout the 3D anisotropic fibrous network during 21 days of culture. Additionally, likewise the hierarchical relationship between chondrocytes and their extracellular matrix, the reported PCL scaffold was able to induce depth-dependent cell-material interactions responsible for promoting a spatial modulation of the morphology, alignment and density of the cells in vitro.

Electrospinning of bioactive polycaprolactone-gelatin nanofibres with increased pore size for cartilage tissue engineering applications.

Polycaprolactone (PCL) electrospun scaffolds have been widely investigated for cartilage repair application. However, their hydrophobicity and small pore size has been known to prevent cell attachment, proliferation and migration. Here, PCL was blended with gelatin (GEL) combining the favorable biological properties of GEL with the good mechanical performance of the former. Also, polyethylene glycol (PEG) particles were introduced during the electrospinning of the polymers blend by simultaneous electrospraying. These particles were subsequently removed resulting in fibrous scaffolds with enlarged pore size. PCL, GEL and PEG scaffolds formulations were developed and extensively structural and biologically characterized. GEL incorporation on the PCL scaffolds led to a considerably improved cell attachment and proliferation. A substantial pore size and interconnectivity increase was obtained, allowing cell infiltration through the porogenic scaffolds. All together these results suggest that this combined approach may provide a potentially clinically viable strategy for cartilage regeneration.

Biomechanical Evidence on Anterior Cruciate Ligament Reconstruction.

Objective Anterior cruciate ligament (ACL) reconstruction is recommended in athletes with high physical demands. Several techniques are used in reconstruction; however, the most relevant question still is the best biomechanical positioning for the graft. The present study aimed to analyze the biomechanical effect of the position of bone tunnels on load distribution and joint kinetics, as well as the medium-term functional outcomes after ACL reconstruction. Methods A biomechanical study using a finite element model of the original knee (without anterior cruciate ligament rupture) and reconstruction of the ACL (neoACL) was performed in four combinations of bone tunnel positions (central femoral-central tibial, anterior femoral-central tibial, posterosuperior femoral-anterior tibial, and central femoral-anterior tibial) using the same type of graft. Each neo-ACL model was compared with the original knee model regarding cartilaginous contact pressure, femoral and meniscal rotation and translation, and ligamentous deformation. Results No neo-ACL model was able to fully replicate the original knee model. When the femoral tunnel was posteriorly positioned, cartilage pressures were 25% lower, and the mobility of the meniscus was 12 to 30% higher compared with the original knee model. When the femoral tunnel was in the anterior position, internal rotation was 50% lower than in the original knee model. Conclusion Results show that the femoral tunnel farther from the central position appears to be more suitable for a distinct behavior regarding the intact joint. The most anterior position increases rotational instability.

Biomechanical Evidence on Anterior Cruciate Ligament Reconstruction / Análise biomecânica da reconstrução do ligamento cruzado anterior

Abstract Objective Anterior cruciate ligament (ACL) reconstruction is recommended in athletes with high physical demands. Several techniques are used in reconstruction; however, themost relevant question still is the best biomechanical positioning for the graft. The present study aimed to analyze the biomechanical effect of the position of bone tunnels on load distribution and joint kinetics, as well as the medium-term functional outcomes after ACL reconstruction. Methods A biomechanical study using a finite element model of the original knee (without anterior cruciate ligament rupture) and reconstruction of the ACL (neoACL) was performed in four combinations of bone tunnel positions (central femoral-central tibial, anterior femoral-central tibial, posterosuperior femoral-anterior tibial, and central femoral-anterior tibial) using the same type of graft. Each neo-ACL model was compared with the original knee model regarding cartilaginous contact pressure, femoral and meniscal rotation and translation, and ligamentous deformation. Results No neo-ACL model was able to fully replicate the original knee model. When the femoral tunnel was posteriorly positioned, cartilage pressures were 25% lower, and the mobility of the meniscus was 12 to 30% higher compared with the original knee model. When the femoral tunnel was in the anterior position, internal rotation was 50% lower than in the original knee model. Conclusion Results show that the femoral tunnel farther from the central position appears to be more suitable for a distinct behavior regarding the intact joint. The most anterior position increases rotational instability.

Resumo Objetivo A reconstrução do ligamento cruzado anterior é aconselhável sobretudo em atletas de alta demanda física. Diversas técnicas são usadas na reconstrução,mas a grande questão é qual o melhor posicionamento para o enxerto. Analisar o efeito biomecânico da posição dos túneis ósseos na repartição de carga e cinemática da articulação, bemcomo os resultados funcionais em médio prazo, após reconstrução do ligamento cruzado anterior. Métodos Fez-se um estudo de simulação biomecânica computacional com modelos de elementos finitos do joelho original e com reconstrução do ligamento cruzado anterior (Neo-LCA) em quatro combinações de posição dos túneis ósseos (femoral central-tibial central, femoral anterior-tibial central, femoral posterossuperior-tibial anterior e femoral central-tibial anterior) com o mesmo tipo de enxerto. Para cada modelo, foram comparadas a pressão de contato na cartilagem, a rotação e translação do fêmur e dos meniscos e a deformação nos ligamentos. Resultados Nenhum modelo de Neo-LCA foi capaz de reproduzir, na íntegra, o modelo do joelho original. Quando o túnel femoral era colocado em posição mais posterior, observaram-se pressões na cartilagem 25% mais baixas e translação dos meniscos superiores entre 12% e 30% relativamente aomodelo intacto. Quando o túnel femoral estava em posição mais anterior, observou-se uma rotação interna do fêmur 50% inferior ao modelo intacto. Conclusão Os resultados evidenciam que uma localização do túnel femoral mais distante da posição central parece ser mais preponderante para um comportamento mais díspar relativamente à articulação intacta. Na posição mais anterior existe um aumento da instabilidade rotatória.

Do biomedical engineers dream of graphene sheets?

During the past few years, graphene has outstandingly emerged as a key nanomaterial for boosting the performance of commercial, industrial and scientific related technologies. The popularity of this novel nanomaterial in biomedical engineering is due to its excellent biological, electronic, optical and thermal properties that, as a whole, surpass the features of commonly used biomaterials and consequently open a wide range of applications so far within the reach of science fiction. In this minireview, the potential of graphene and its based materials in the expanding biomedical field is highlighted with focus on groundbreaking diagnostic, monitoring and therapeutic strategies. Some of the major challenges related to the synthesis and safety of graphene-based materials are also briefly discussed because of their critical importance in bringing this class of carbon materials closer to the clinic.

A mathematical model of tissue-engineered cartilage development under cyclic compressive loading.

In this work a coupled model of solute transport and uptake, cell proliferation, extracellular matrix synthesis and remodeling of mechanical properties accounting for the impact of mechanical loading is presented as an advancement of a previously validated coupled model for free-swelling tissue-engineered cartilage cultures. Tissue-engineering constructs were modeled as biphasic with a linear elastic solid, and relevant intrinsic mechanical stimuli in the constructs were determined by numerical simulation for use as inputs of the coupled model. The mechanical dependent formulations were derived from a calibration and parametrization dataset and validated by comparison of normalized ratios of cell counts, total glycosaminoglycans and collagen after 24-h continuous cyclic unconfined compression from another dataset. The model successfully fit the calibration dataset and predicted the results from the validation dataset with good agreement, with average relative errors up to 3.1 and 4.3 %, respectively. Temporal and spatial patterns determined for other model outputs were consistent with reported studies. The results suggest that the model describes the interaction between the simultaneous factors involved in in vitro tissue-engineered cartilage culture under dynamic loading. This approach could also be attractive for optimization of culture protocols, namely through the application to longer culture times and other types of mechanical stimuli.

Influence of the scaffold geometry on the spatial and temporal evolution of the mechanical properties of tissue-engineered cartilage: insights from a mathematical model.

The production of tissue-engineered cartilage in vitro with inhomogeneous mechanical properties is a problem yet to be solved. Different geometries have been studied to overcome this caveat; however, the reported measurements are limited to average values of some properties and qualitative measures of spatial distributions. We will apply a coupled model to extend knowledge about the introduction of a macrochannel in a scaffold by calculating spatiotemporal patterns for several interest variables related to the remodeling of the mechanical properties. Model parameters were estimated based on experimental data on the temporal patterns of glycosaminoglycans, collagen and compressive Young's modulus for channel-free constructs. The model reproduced the experimental data trends in both geometries, with experimental-numerical correlations between 0.84 and 0.97. The channel had a higher impact on the reduction in spatial heterogeneities and delay of saturation of core properties than in the improvement of average properties. Despite the possible improvement of cell densities for longer periods than 56 days, it is estimated that it will not cause further significant improvements of the mechanical properties. The degrees of spatial heterogeneity of the Young's modulus and permeability in the channeled geometry are 23 and 27 % of the channel-free values. While the average Young's modulus values are in the range of native cartilage, the permeabilities are one to three degrees of magnitude higher than the native cartilage, suggesting that limiting factors such as scaffold porosity and initial permeability are more relevant than scaffold geometry to effectively decrease the tissue permeability.

Failure analysis of C-5 after total disc replacement with ProDisc-C at 1 and 2 levels and in combination with a fusion cage: finite-element and biomechanical models.

OBJECT The purpose of this study was to evaluate the failure risk of cervical vertebrae after total disc replacement with a keel-design prosthesis (ProDisc-C), taking into consideration the effects of vertebral body height, multilevel replacement, and the association with an adjacent fusion cage. Although promising clinical results have been reported for the ProDisc-C, some clinical studies have reported vertebral body-splitting fractures at single- and multilevel arthroplasty sites. This implant has central keels to provide solid initial stability, and some authors associate the potential risk of vertebral body failure with the keel design, especially in patients with small vertebral body height or when the implant is used at multiple levels. METHODS The study was performed using a specimen-specific C4-6 cervical-segment finite-element model to assess the compressive strains on the C-5 vertebral body for each cervical segment configuration, and synthetic polyurethane models to experimentally predict the compressive load at failure for 3 vertebral body heights. RESULTS The use of a keeled ProDisc-C prosthesis at multiple levels or in combination with a fusion cage increases by a factor of 2-3 the compressive strains at the C-5 vertebral body relative to single-level arthroplasty. All implanted segment configurations tested demonstrated a continuum of the load at failure and the vertebral body height, but no significant differences were found between the 3 vertebral body heights in each segment configuration. CONCLUSIONS The use of a keeled ProDisc-C prosthesis at 2 adjacent levels or combined with a fusion cage presented the lowest load-at-failure values, 2 times higher on average than the ones occurring during physiological tasks. This fact indicates an identical and limited risk of vertebral body failure for these 2 segment configurations, whereas vertebral body height appears to slightly affect this risk. However, for some tasks that place higher physical demands on the neck, beyond what was represented by our models, there may also be risk of microdamage initiation, which is not present in the single-level arthroplasty.