Progression of partial to complete ruptures of the Achilles tendon during rehabilitation: A study using a finite element model.

Substantial research on complete Achilles tendon ruptures is available, but guidance on partial ruptures is comparatively sparse. Conservative management is considered acceptable in partial tendon ruptures affecting less than 50% of the tendon's width, but supporting experimental evidence is currently lacking. Using a previously validated finite element model of the Achilles tendon, this study aimed to assess whether loading conditions simulating an early functional rehabilitation protocol could elicit progression to a complete rupture in partial ruptures of varying severity. In silico tendon rupture simulations were performed to locate the most likely rupture site for least, moderate, and extreme subtendon twist configurations. These three models were split at the corresponding rupture site and two sets of partial ruptures were created for each, starting from the medial and lateral sides, and ranging from 10% to 50% loss of continuity. Simulations were conducted with material parameters from healthy and tendinopathic tendons. Partial ruptures were considered to progress if the volume of elements showing a maximum principal strain above 10% exceeded 3 mm3 . To assess whether the tendinopathic tendons typical geometric characteristics could compensate for the inferior material properties found in tendinopathy, an additional model with increased cross-sectional area in the free tendon region was developed. Progression to complete ruptures occurred even with less than a 50% loss of continuity, regardless of subtendon twisting, and material parameters. The tendinopathic tendon model with increased cross-sectional area showed similar results. These findings suggest the current criteria for surgical treatment of partial ruptures should be reconsidered. Statement of clinical significance: The clinical significance and most appropriate treatment of partial ruptures of the Achilles tendon is unclear. Despite the widespread use of the "50% rule" in treatment decisions of partial tendon ruptures, experimental evidence supporting it is missing. The present study provides new data, from a validated aponeurotic and free Achilles tendon finite element model, showing that partial ruptures may progress to complete ruptures under loading conditions elicited from functional rehabilitation protocols, even for partial ruptures affecting less than 50% of the tendon's width. Under these novel findings, the current criteria for surgical treatment of partial ruptures should be reconsidered.

Influence of the rotator cuff tear pattern in shoulder stability after arthroscopic superior capsule reconstruction: a computational analysis.

OBJECTIVES: To assess the ability of the arthroscopic superior capsule reconstruction (SCR) in restoring glenohumeral stability in the presence of different preoperative patterns of irreparable rotator cuff tears (RCTs). METHODS: A computational musculoskeletal (MSK) model of the upper limb was used to simulate isolated SCR and to estimate the stability of the shoulder. Four patterns of preoperative irreparable RCTs were modeled: Supraspinatus (SSP); SSP â€‹+ â€‹Subscapularis (SSC); SSP â€‹+ â€‹Infraspinatus (ISP); and SSP â€‹+ â€‹SSC â€‹+ â€‹ISP. The muscles involved in the irreparable RCT were removed from the MSK model to simulate an irreparable full-thickness tear. In the MSK model, the muscle and joint forces were estimated for a set of upper limb positions, from four types of motions (abduction in the frontal plane, forward flexion in the sagittal plane, reaching behind the back, and combing the hair) collected in a biomechanics laboratory, through inverse dynamic analysis. The stability of the shoulder was estimated based on the tangential and compressive components of the glenohumeral joint reaction force. The comparison of pre- and post-operative conditions, for the four patterns of irreparable RCTs, with the healthy condition, was performed using ANOVA and Tukey's tests (statistical level of p â€‹< â€‹0.05). RESULTS: In the setting of an isolated irreparable SSP tear, SCR statistically significantly improved stability compared with the preoperative condition (p â€‹< â€‹0.001). For the irreparable SSP â€‹+ â€‹SSC pattern, a statistically significant loss in stability was observed (p â€‹< â€‹0.001) when SCR was applied. For the irreparable SSP â€‹+ â€‹ISP and SSP â€‹+ â€‹SSC â€‹+ â€‹ISP patterns, the postoperative condition increased shoulder stability, compared to the preoperative condition; however, the improvement was not statistically significantly different. CONCLUSION: Isolated SCR for irreparable RCTs extending beyond the SSP does not statistically significantly improve the stability of the glenohumeral joint. LEVEL OF EVIDENCE: Level IV.

Design and validation of a finite element model of the aponeurotic and free Achilles tendon.

The Achilles tendon (AT) is a common injury site. Ruptures are usually located in the free tendon but may cross the myotendinous junction into the aponeurotic region. Considering the possibility of aponeurotic region involvement in AT ruptures, a novel three dimensional (3D) finite element (FE) model that includes both the aponeurotic and free AT regions and features subtendon twisting and sliding was developed. It was hypothesized that the model would be able to predict in vivo data collected from the literature, thus being considered valid, and that model outputs would be most sensitive to subtendon twist configurations. The 3D model was constructed using magnetic resonance images. The model was divided into soleus and gastrocnemius subtendons. In addition to a frictionless contact condition, the interaction between subtendons was modeled using two contact formulations: sliding with anisotropic friction and no sliding. Loads were applied on the tendon's most proximal cross-section and anterior surface, with magnitudes estimated from in vivo studies. Model outputs were compared with experimental data regarding 3D deformation, transverse plane rotation, and nodal displacements in the free tendon. The FE model adequately simulated the free tendon behavior regarding longitudinal strain, cross-section area variation, transverse plane rotation, and sagittal nodal displacements, provided that subtendon sliding was allowed. The frictionless model exhibited noticeable medial transverse sliding of the soleus subtendon, which was present to a much lesser degree in the anisotropic friction model. Model outputs were most sensitive to variations in subtendon twist and dispersion of the collagen fiber orientations. Clinical Significance: This Achilles tendon finite element model, validated using in vivo experimental data, may be used to study its mechanical behavior, injury mechanisms, and rupture risk factors.

Influence of Graft Positioning during the Latarjet Procedure on Shoulder Stability and Articular Contact Pressure: Computational Analysis of the Bone Block Effect.

The Latarjet procedure is the most popular surgical procedure to treat anterior glenohumeral (GH) instability in the presence of large anterior glenoid bone defects. Even though the placement of the bone graft has a considerable influence on its efficacy, no clear indications exist for the best graft position. The aim of this study was to investigate the influence of the medial-lateral positioning of the bone graft on the contact mechanics and GH stability due to the bone block effect. Four finite element (FE) models of a GH joint, with a 20% glenoid bone defect, treated by the Latarjet procedure were developed. The FE models differed in the medial-lateral positioning of the bone graft, ranging from a flush position to a 4.5 mm lateral position with respect to the flush position. All graft placement options were evaluated for two separate shoulder positions. Anterior GH instability was simulated by translating the humeral head in the anterior direction, under a permanent compressive force, until the peak translation force was reached. Joint stability was computed as the ratio between the shear and the compressive components of the force. The lateralization of the bone graft increased GH stability due to the bone block effect after a 3 mm lateralization with respect to the flush position. The increase in GH stability was associated with a concerning increase in peak contact pressure due to the incongruous contact between the articulating surfaces. The sensitivity of the contact pressures to the medial-lateral positioning of the bone graft suggests a trade-off between GH stability due to the bone block effect and the risk of osteoarthritis, especially considering that an accurate and consistent placement of the bone graft is difficult in vivo.

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.

Metaphyseal sleeves in revision total knee arthroplasties: Computational analysis of bone remodeling.

BACKGROUND: Metaphyseal sleeves help maintain long term stability and reduce revision rate for aseptic loosening in total knee arthroplasty (TKA) revision. However, their performance regarding bone remodeling is still poorly known for the long term. This study aimed to investigate the impact of metaphyseal sleeves on the bone remodeling of the tibia. METHODS: Five finite element models of a female tibia with different implant configurations (regarding stem length and metaphyseal sleeve application) were developed. Loading conditions included joint reaction force, muscle, and tibia-fibula loads from 6 instances of the gait cycle. The bone remodeling model applied was adapted to the subject under analysis by selecting the bone remodeling parameters that best replicated the bone density distribution of the tibia estimated from the CT data. Changes in bone density after TKA were evaluated in 8 regions of interest. RESULTS: Global bone loss ranged from -31.16%, in 115 mm stemmed configurations, to -20.93%, in 75 mm stemmed configurations. Apart from the lateral and posterior regions in the proximal tibia, whose bone loss reduced and increased, respectively, due to the incorporation of a metaphyseal sleeve, changes in bone density were similar with and without a metaphyseal sleeve for each stem length. CONCLUSION: The results suggest that bone remodeling of the tibia is not critically affected by the incorporation of metaphyseal sleeves. Considering that sleeves are believed to present a favorable clinical outcome in stability and osseointegration, reducing the revision rate for aseptic loosening, their advantages seem to outweigh their disadvantages regarding bone remodeling.

Shoulder Positioning during Superior Capsular Reconstruction: Computational Analysis of Graft Integrity and Shoulder Stability.

The shoulder position during fixation of the graft may be a key factor impacting the outcome of arthroscopic superior capsular reconstruction (ASCR) in irreparable rotator cuff tears (IRCTs). However, biomechanical evidence regarding this effect is lacking. The aim of this study was to evaluate the influence of the shoulder position during fixation of the graft on shoulder stability and graft tear risk in ASCR. A 3-D musculoskeletal model of the upper limb was modified to account for the fixation of the graft in ASCR, assuming a full-thickness tear of the supraspinatus tendon. The concomitant tenotomy of the long head of the biceps (LHB) tendon was also studied. The biomechanical parameters evaluated included the strain of the graft and the glenohumeral joint reaction force (GH JRF), which were used to evaluate graft integrity and shoulder stability, respectively. Fixation of the graft considering abduction angles greater than 15° resulted in a high risk for graft tearing when the arm was adducted to the side of the trunk. For abduction angles below 15°, the mean shoulder stability improved significantly, ranging between 6% and 20% (p < 0.001), compared with that in the preoperative condition. The concomitant tenotomy of the LHB tendon resulted in loss of stability when compared to ASCR with an intact LHB tendon. The position of the shoulder during fixation of the graft has a significant effect on shoulder stability and graft tear risk after ASCR in IRCTs. This study provides new and important information regarding the role of shoulder positioning during fixation of the graft.

Influence of the PFNA screw position on the risk of cut-out in an unstable intertrochanteric fracture: a computational analysis.

The position of the lag screw in the femoral head is a key factor to cut-out, the most reported complication in the internal fixation of intertrochanteric fractures. Considering that the best position for the lag screw remains controversial, the aim of this study was to evaluate the influence of different lag screw positions on the risk of cut-out of an unstable intertrochanteric fracture fixed with a Proximal Femoral Nail Anti-Rotation (PFNA) implant. The relationship between cut-out and the tip-apex distance (TAD) or the calcar referenced tip-apex distance (CalTAD) was also investigated. Finite element models of one male and one female femur treated with a PFNA implant were developed considering the lag screw positioned centrally and inferiorly on the anteroposterior view, and for each of these, the screw tip at 4 discrete positions along its longitudinal axis. All 8 positions simulated for each femur considered the lag screw in a centre position on the lateral view. The risk of cut-out was evaluated for two loading conditions assuming it is related with high compressive strains. The bone region at the fracture line, near the tip of the missing medial fragment, was always the most concerning regarding high compressive strains. The inferior positioning of the lag screw reduced the volume of bone susceptible to yielding compared to the centre positioning. The deep placement of the screw tip improved the outcome for both centre and inferior positions. The results suggested the inferior and deep placement of the screw to be the best position to reduce the risk of cut-out. The volume of bone susceptible to yielding was found not to be correlated to TAD or CalTAD, suggesting that further investigation is necessary to identify other, more reliable, predictors of cut-out.

Proximal and mid-thigh fascia lata graft constructs used for arthroscopic superior capsule reconstruction show equivalent biomechanical properties: an in vitro human cadaver study.

BACKGROUND: The proximal fascia lata (FL) graft construct used for arthroscopic superior capsule reconstruction (ASCR) is openly harvested, whereas the mid-thigh FL graft construct is minimally invasively harvested. The purpose of the current study was to compare the biomechanical properties of proximal thigh and mid-thigh-harvested FL graft constructs used for ASCR. The hypothesis was that, despite the different morphological characteristics of the proximal thigh and mid-thigh FL graft constructs used for ASCR, their biomechanical properties would not significantly differ. This information may assist orthopedic surgeons in the choice of the harvest location, technique, and type of graft construct for ASCR. METHODS: Forty FL specimens, 20 proximal thigh and 20 mid-thigh, were harvested from the lateral thighs of 10 fresh human cadavers (6 male, 4 female; average age, 58.60 ± 17.20 years). The thickness of each 2-layered proximal thigh and 6-layered mid-thigh FL graft construct was measured. Each construct was mechanically tested in the longitudinal direction, and the stiffness and Young's modulus were computed. Data were compared by Welch's independent t-test and analysis of variance, and statistical significance was set at P < .05. RESULTS: The average thickness of the proximal thigh FL graft construct (7.17 ± 1.97 mm) was significantly higher than that of the mid-thigh (5.54 ± 1.37 mm) [F (1,32) = 7.333, P = .011]. The average Young's modulus of the proximal thigh and mid-thigh graft constructs was 32.85 ± 19.54 MPa (range, 7.94 - 75.14 MPa; 95% confidence interval [CI], 23.71 - 42.99) and 44.02 ± 31.29 MPa (range, 12.53 -120.33 MPa; 95% CI, 29.38 - 58.66), respectively. The average stiffness of the proximal thigh and mid-thigh graft constructs was 488.96 ± 267.80 N/mm (range, 152.96 - 1086.49 N/mm; 95% CI, 363.63 - 614.30) and 562.39 ± 294.76 N/mm (range, 77.46 - 1229.68 N/mm; 95% CI, 424.44 - 700.34), respectively. There was no significant difference in the average Young's modulus or stiffness between the proximal thigh and mid-thigh graft constructs (P = .185 and P = .415, respectively). CONCLUSION: Despite the different morphological characteristics of the proximal thigh and mid-thigh FL graft constructs used for ASCR, their Young's modulus and stiffness did not significantly differ.

Surrogate-based multi-objective design optimization of a coronary stent: Altering geometry toward improved biomechanical performance.

The main objective of this study was to solve a multi-objective optimization on a representative coronary stent platform with the goal of finding new geometric designs with improved biomechanical performance. The following set of metrics, calculated via finite element models, was used to quantify stent performance: vessel injury, radial recoil, bending resistance, longitudinal resistance, radial strength and prolapse index. The multi-objective optimization problem was solved with the aid of surrogate-based algorithms; for comparison and validation purposes, four surrogate-based multi-objective optimization algorithms (EIhv -EGO, Phv -EGO, ParEGO and SMS-EGO) with a limited sample budget were employed and their results compared. The quality of the non-dominated solution sets outputted by each algorithm was assessed against four quality indicators: hypervolume, R2, epsilon and generational distance. Results showed that Phv -EGO was the algorithm that exhibited the best performance in overall terms. Afterwards, the highest quality Pareto front was chosen for an in-depth analysis of the optimization results. The amount of correlation and conflict was quantified for each pair of objective functions. Next, through cluster analysis, one was able to identify families of solutions with similar performance behavior and to discuss the nature of the existent trade-offs between objectives, and the trends between design parameters and solutions in a biomechanical perspective. In the end, a constrained-based design selection was performed with the goal of finding solutions in the Pareto front with equal or better performance in all objectives against a baseline design.

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.

Stress analysis in a bone fracture fixed with topology-optimised plates.

The design of commercially available fixation plates and the materials used for their fabrication lead to the plates being stiffer than bone. Consequently, commercial plates are prone to induce bone stress shielding. In this study, three-dimensional fixation plates are designed using topology optimisation aiming to reduce the risk of bone stress shielding. Fixation plate designs were optimised by minimising the strain energy for three levels of volume reduction (i.e. 25%, 45% and 75%). To evaluate stress shielding, changes in bone stress due to the different fixation plate designs were determined on the fracture plane of an idealised shaft of a long bone under a four-point bending load considering the effect of a patient walking with crutches of a transverse fractured tibia. Topology optimisation is a viable approach to design less stiff plates with adequate mechanical strength considering high volume reductions, which consequently increased the stress transferred to the bone fracture plane minimising bone stress shielding.

Bone adaptation impact of stemless shoulder implants: a computational analysis.

BACKGROUND: Despite stemless implants showing promising functional and radiologic clinical outcomes, concerning signs of complications, such as bone resorption, have been reported. The aim of this study was to investigate the influence of 5 stemless designs on the bone adaptation process of the humerus. METHODS: Three-dimensional finite element models of shoulder arthroplasties were developed considering stemless designs based on the Eclipse, Global Icon, SMR, Simpliciti, and Sidus stemless systems. For the designs not possessing a collar that covers the entire resected surface of the humerus, conditions of contact and no contact were simulated between the humeral head components and the bone surface. By use of a bone remodeling model, computational simulations were performed considering 6 load cases of standard shoulder movements. The bone adaptation process was evaluated by comparing differences in bone density between the implanted models and the intact model of the humerus. RESULTS: Overall, the design of the stemless implants had a relevant impact on the bone adaptation process of the humerus. The Eclipse-based design caused the largest bone mass loss, whereas the SMR-based design caused the least. When contact was simulated between the humeral head components of the SMR-, Simpliciti-, and Sidus-based designs and the resected bone surface, bone resorption increased. DISCUSSION: Considering only the bone adaptation process, the results suggest that the SMR-based implant presents the best performance and that contact between the humeral head component and the resected bone surface should be avoided. However, because other factors must be considered, further investigation is necessary to allow definite recommendations.

Surrogate-based visualization and sensitivity analysis of coronary stent performance: A study on the influence of geometric design.

The main goal of this numerical study is to assess the impact of geometric design perturbations on the performance of a representative coronary stent platform. In this context, first, a design parameterization model was defined for the stent under study. After, a set of metrics characterizing stent performance, namely, vessel injury, radial recoil, bending resistance, longitudinal resistance, radial strength, the risk of fracture, prolapse index, and dogboning were evaluated within the context of a finite element analysis. Afterwards, accurate surrogate models were developed, using the efficient global optimization algorithm, as predictive tools in the execution of tasks that normally require a high number of model evaluations, such as global sensitivity analysis and visualization. In the end, the dependence of the output response surfaces on the geometric parameters was mechanically interpreted, which allowed us to understand the complex interplay that exists between the considered design variables and the defined performance metrics.

Automated femoral landmark extraction for optimal prosthesis placement in total hip arthroplasty.

The automated extraction of anatomical reference landmarks in the femoral volume may improve speed, precision, and accuracy of surgical procedures, such as total hip arthroplasty. These landmarks are often hard to achieve, even via surgical incision. In addition, it provides a presurgical guidance for prosthesis sizing and placement. This study presents an automated workflow for femoral orientation and landmark extraction from a 3D surface mesh. The extraction of parameters such as the femoral neck axis, the femoral middle diaphysis axis, both trochanters and the center of the femoral head will allow the surgeon to establish the correct position of bony cuts to restore leg length and femoral offset. The definition of the medullary canal endosteal wall is used to position the prosthesis' stem. Furthermore, prosthesis alignment and sizing methods were implemented to provide the surgeon with presurgical information about performance of each of the patient-specific femur-implant couplings. The workflow considers different commercially available hip stems and has the potential to help the preoperative planning of a total hip arthroplasty in an accurate, repeatable, and reliable way. The positional and orientation errors are significantly reduced, and therefore, the risk of implant failure and subsequent revision surgery are also reduced.

Computational design and fabrication of a novel bioresorbable cage for tibial tuberosity advancement application.

Tibial tuberosity advancement (TTA) is a promising method for the treatment of cruciate ligament rupture in dogs that usually implies the implantation of a titanium cage as bone implant. This cage is non-biodegradable and fails in providing adequate implant-bone tissue integration. The objective of this work is to propose a new process chain for designing and manufacturing an alternative biodegradable cage that can fulfill specific patient requirements. A three-dimensional finite element model (3D FEM) of the TTA system was first created to evaluate the mechanical environment at cage domain during different stages of the dog walk. The cage microstructure was then optimized using a topology optimization tool, which addresses the accessed local mechanical requirements, and at same time ensures the maximum permeability to allow nutrient and oxygen supply to the implant core. The designed cage was then biofabricated by a 3D powder printing of tricalcium phosphate cement. This work demonstrates that the combination of a 3D FEM with a topology optimization approach enabled the design of a novel cage for TTA application with tailored permeability and mechanical properties, that can be successfully 3D printed in a biodegradable bioceramic material. These results support the potential of the design optimization strategy and fabrication method to the development of customized and bioresorbable implants for bone repair.

Fully automatic segmentation of femurs with medullary canal definition in high and in low resolution CT scans.

Femur segmentation can be an important tool in orthopedic surgical planning. However, in order to overcome the need of an experienced user with extensive knowledge on the techniques, segmentation should be fully automatic. In this paper a new fully automatic femur segmentation method for CT images is presented. This method is also able to define automatically the medullary canal and performs well even in low resolution CT scans. Fully automatic femoral segmentation was performed adapting a template mesh of the femoral volume to medical images. In order to achieve this, an adaptation of the active shape model (ASM) technique based on the statistical shape model (SSM) and local appearance model (LAM) of the femur with a novel initialization method was used, to drive the template mesh deformation in order to fit the in-image femoral shape in a time effective approach. With the proposed method a 98% convergence rate was achieved. For high resolution CT images group the average error is less than 1mm. For the low resolution image group the results are also accurate and the average error is less than 1.5mm. The proposed segmentation pipeline is accurate, robust and completely user free. The method is robust to patient orientation, image artifacts and poorly defined edges. The results excelled even in CT images with a significant slice thickness, i.e., above 5mm. Medullary canal segmentation increases the geometric information that can be used in orthopedic surgical planning or in finite element analysis.

In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2.

The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2) has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies.

Critical analysis of musculoskeletal modelling complexity in multibody biomechanical models of the upper limb.

The inverse dynamics technique applied to musculoskeletal models, and supported by optimisation techniques, is used extensively to estimate muscle and joint reaction forces. However, the solutions of the redundant muscle force sharing problem are sensitive to the detail and modelling assumptions of the models used. This study presents four alternative biomechanical models of the upper limb with different levels of discretisation of muscles by bundles and muscle paths, and their consequences on the estimation of the muscle and joint reaction forces. The muscle force sharing problem is solved for the motions of abduction and anterior flexion, acquired using video imaging, through the minimisation of an objective function describing muscle metabolic energy consumption. While looking for the optimal solution, not only the equations of motion are satisfied but also the stability of the glenohumeral and scapulothoracic joints is preserved. The results show that a lower level of muscle discretisation provides worse estimations regarding the muscle forces. Moreover, the poor discretisation of muscles relevant to the joint in analysis limits the applicability of the biomechanical model. In this study, the biomechanical model of the upper limb describing the infraspinatus by a single bundle could not solve the complete motion of anterior flexion. Despite the small differences in the magnitude of the forces predicted by the biomechanical models with more complex muscular systems, in general, there are no significant variations in the muscular activity of equivalent muscles.

Is the callus shape an optimal response to a mechanobiological stimulus?

After bone trauma, the natural response to restore bone function is the formation of a callus around the fracture. Although several bone healing models have been developed, none have effectively perceived early callus formation and shape as the result of an optimal response to a mechanobiological stimulus. In this paper, we investigate which stimulus regulates early callus formation. An optimal design problem is formulated, and several objective functions are defined, each using a different mechanobiological stimulus. The following stimuli were analysed: the interfragmentary strain, the second invariant of the deviatoric strain tensor and a generic inflammatory factor. Different regions for callus formation were also evaluated, such as the gap region, the periosteum and the periosteum border. Each stimulus was computed using the finite element method, and the callus shape was optimised using the steepest descent method. The results demonstrated that the inflammatory factor approach, the interfragmentary strain and the second invariant of the deviatoric strain tensor over the inner gap provided the best results when compared with histological callus shapes. Therefore, this work suggests that callus growth can be an optimal mechanobiological response to either local mechanical instability and/or local inflammatory reaction.