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Regenerating osteoporotic bone remains challenging due to healing complications such as non-unions. Distraction osteogenesis is a promising technique for bone repair, but its efficacy under osteoporotic conditions is poorly understood. This study provides quantitative translational knowledge on the influence of osteoporosis in distraction callus mechanics. Fifteen Merino sheep were induced with osteoporosis. A 15 mm bone defect in the right hind metatarsus was treated with distraction osteogenesis and stabilized with an instrumented external fixator. Callus distraction forces and relaxation were recorded and modeled to assess the viscoelastic behavior of the organic matrix. Callus ossification and mechanics were assessed using x-ray imaging and gait analysis. The results were compared to those from similar studies involving non-osteoporotic subjects. Osteoporosis significantly reduced distraction force peaks and relaxation ( < 0.05), with effects diminishing over the relaxation time. The elastic component of the organic matrix, especially ground substance, was significantly impaired ( < 0.05). X-ray follow-up and gait analysis revealed that half of the pathologic animals recovered comparably to non-osteoporotic subjects, while the others exhibit lateralized mineralization and reduced load bearing capacity. Osteoporosis led to a 50% reduction in the viscoelastic response of the distraction callus, likely due to an impaired osteoblastic matrix synthesis. Furthermore, osteoporotic patients undergoing distraction osteogenesis for critical-size defects may experience delayed consolidation with heterogeneous mineralization, which may be linked to early deficits in organic matrix formation.

Background External fixation has been one of the conventional managements of unstable distal radius fracture. The main aim of this paper is to compare two methods of applying distractive force along the radius shaft versus perpendicular to the distal radius articular surface. Design Sixty patients with unstable distal radius fracture were included in present clinical trial and randomized in two groups, using block randomization method. In group A (first arm), distraction force was exerted parallel to the radius shaft. In group B (second arm), the external fixator was adjusted based on radial and palmar tilt of the mean population healthy wrist so that distraction was exerted perpendicular to the wrist articular surface. Methods Radiological and clinical parameters were evaluated in both groups of patients pre-operatively, immediately after surgery, and 6 weeks post-operatively. We also followed up patients clinically at 12 weeks after surgery. Patient-Rated Wrist Evaluation (PRWE), Mayo wrist score, and Quick Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires were used in order to assess patients’ clinical and functional states. Results The method used in group B resulted in better improvement of palmar tilt both immediately ( P  = 0.007) and at 6 weeks follow up ( P  = 0.013) post-operatively in comparison with patients in group A. Radius height and radial inclination were also better restored when using the proposed modified method ( P  = 0.001 and < 0.001, respectively). There was no difference in any of clinical results (range of motion, grip strength, PRWE, Mayo, and DASH scores) between two groups of study, 12 weeks after surgery. Conclusion Applying distractive force perpendicular to the distal radius articular surface seems to improve some radiological outcomes, probably due to better reduction maintenance, when compared with the technique of applying distraction force along distal radius shaft axis. Level of Evidence Level I (clinical trial study). Trial registration This study is registered at Iranian Registry of Clinical Trials (IRCT) with approval code of IRCT20200313046759N1.

Bone lengthening is a bone regeneration technique with multiple clinical applications. One of the most common complications of this treatment is the lack of adaptation of the surrounding soft tissue to their extension. A better understanding of the mechanobiology of the tissues involved in distraction osteogenesis would allow better control of the clinical cases. Bone lengthening treatments were performed in vivo in the metatarsus of Merino sheep, measuring the distraction forces by means of an instrumented fixator. The tissue relaxation after distraction was analyzed in this study. A viscoelastic model was also applied to distraction data to assess the mechanical behavior of the tissues during the distraction phase. Tissue relaxation is similar to other bone regeneration processes which do not imply surrounding soft tissue extension, e.g. bone transport. The effects of this tissue on distraction forces are limited to the first minutes of distraction and elongations above 4% of the original length with the protocol applied. Moreover, the surrounding soft tissue initially loses some of its viscoelasticity and subsequently suffers strain hardening from day 5 of distraction until the end of the distraction phase, day 15. Finally, anatomical changes were also evidenced in the elongated limb of our specimens.

Purpose: To investigate the theoretical forces involved in and the nature of fixation between the modular components of a variety of aortic stent-grafts. Methods: An in vitro study of 6 aortic stent-grafts was performed using a tensometer. The modular stent-graft components were distracted until the iliac limb was completely separated from the main body. Tests were repeated at least 6 times for each stent-graft. Results: The maximum pullout force was 36.0 N using the Fortron stent-graft, which resulted in stent-graft disintegration. The maximum median forces of the other stent-grafts were 23.7 N (19.9–31.2) for the Aorfix, 7.3 N (6.9–7.6) for the AneuRx, 7.0 N (6.8–7.1) for the Zenith BiFab, 5.4 N (5.0–6.5) for the Talent, and 2.4 N (2.2–2.4) for the Vanguard II Conclusion: The results of this in vitro study suggest that current forms of iliac limb fixation in modular aortic stent-grafts are adequate provided the components are deployed with sufficient overlap. However, for many of the stent-grafts tested, the safety margin was small.

The underlying mechanism of the trans-sutural distraction osteogenesis (TSDO) technique as an effective treatment that improves the symptoms of midfacial hypoplasia syndromes is not clearly understood. Increasing findings in the orthopedics field indicate that macrophages are mechanically sensitive and their phenotypes can respond to mechanical cues. However, how macrophages respond to mechanical stretching and consequently influence osteoblast differentiation of suture-derived stem cells (SuSCs) remains unclear, particularly during the TSDO process. In the present study, we established a TSDO rat model to determine whether and how macrophages were polarized in response to stretching and consequently affected bone regeneration of the suture frontal edge. Notably, after performing immunofluorescence, RNA-sequencing, and micro-computed tomography, it was demonstrated that macrophages are first recruited by various chemokines factors and polarized to the M2 phenotype upon optimal stretching. The latter in turn regulates SuSC activity and facilitates bone regeneration in sutures. Moreover, when the activated M2 macrophages were suppressed by pharmacological manipulation, new bone microarchitecture could rarely be detected under mechanical stretching and the expansion of the sutures was clear. Additionally, macrophages achieved M2 polarization in response to the optimal mechanical stretching (10%, 0.5 Hz) and strongly facilitated SuSC osteogenic differentiation and human umbilical vein endothelial cell angiogenesis using an indirect co-culture system in vitro. Collectively, this study revealed the mechanical stimulation-immune response-bone regeneration axis and clarified at least in part how sutures achieve bone regeneration in response to mechanical force.

Understanding the evolution of callus mechanical properties over time provides insights in the mechanobiology of fracture healing and tissue differentiation, can be used to validate numerical models, and informs clinical practice. Bone transport experiments were performed in sheep, in which a distractor type Ilizarov was implanted. The forces through the fixator evolution were measured and the callus stiffness was estimated from these forces. Computerized tomography images were taken and bone volume of the callus at different stages was obtained. The results showed that the maximum bone tissue production rate (0.146 cm 3 /day) was achieved 20 days after the end of the distraction phase. 50 days after the end of the distraction phase, the callus was ossified completely and had its maximum volume, 6–10 cm 3 . In addition, 80–90% of the load sustained by the operated limb was recovered and the callus stiffness increased exponentially until 5.4–11.4 kN/mm, still below 10% of the healthy level of callus stiffness. The effects of the bony bridging of the callus and the time of the fixator removal on callus force, stiffness and volume were analyzed. These outcomes allowed relating quantifiable biological aspects (callus volume and tissue production rate) with mechanical parameters (callus force and stiffness) using data from the same experiment.

Thumb carpometacarpal joint space changes when the surrounding soft tissues including the capsule, ligaments, and tendons are stretched or pulled away. When at rest, joint forces originate from passive contraction of muscles and the involvement of joint capsule and ligaments. Previous biomechanical models of hand and finger joints have mostly focused on the assessment of joint properties when muscles were active. This study aims to present an experimental-numerical biomechanical model of thumb carpometacarpal joint to explore the contribution of tendons, ligaments, and other soft tissues in the passive forces during distraction. Five fresh cadaveric specimens were tested using a distractor device to measure the applied forces upon gradual distraction of the intact joint. The subsequent step involved inserting a minuscule sensor into the joint capsule through a small incision, while preserving the integrity of tendons and ligaments, in order to accurately measure the fundamental intra-articular forces. A numerical model was also used to calculate the passive forces of tendons and ligaments. Before the separation of bones, the forces exerted by tendons and ligaments were relatively small compared to the capsule force, which accounted for approximately 92% of the total applied force. Contribution of tendons and ligaments, however, increased by further distraction. The passive force contribution by tendons at 2-mm distraction was determined less than 11%, whereas it reached up to 74% for the ligaments. The present study demonstrated that the ligament-capsule complex plays significant contribution in passive forces of thumb carpometacarpal joint during distraction.

Knee ligaments guide and restrain joint motion, and their properties influence joint mechanics. Inverse modeling schemes have been used to estimate specimen-specific ligament properties, where external joint forces are assumed to balance with internal ligament and contact forces. This study simplifies this assumption by adjusting experimental loads to remove internal contact forces. The purpose of this study was to use novel experimental loading in an inverse modeling scheme to estimate ligament slack lengths, perform validation using additional loading scenarios, and evaluate sensitivity to the applied loading. Joint kinematics and kinetics were experimentally measured for a set of load cases. An optimization scheme used a specimen-specific forward kinematics model to estimate ligament slack lengths by minimizing the residual between model and experimentally measured kinetics. The calibrated model was used for a form of validation by evaluating non-optimized load cases. Additionally, uncertainty analysis related kinetic errors to previously reported kinematic errors. The six DOF tibial reactions realized RMS errors less than 23 N and 0.75 Nm for optimized load cases, and 33 N and 2.25 Nm for the non-optimized load cases. The uncertainty analysis, which was performed using the optimized load cases, showed average kinetic RMS errors less than 26 N and 0.45 Nm. The model’s recruitment patterns were similar to those found in clinical and cadaveric studies. This study demonstrated that experimental distraction loading can be used in an inverse modeling scheme to estimate ligament slack lengths with a forward kinematics model.

The Ilizarov technique has been continuously innovated to utilize tensile stress (TS) for inducing a bone development‐like regenerative process, aiming to achieve skeletal elongation and reconstruction. However, it remains uncertain whether this distraction osteogenesis (DO) process induced by TS involves the pivotal coupling of angiogenesis and osteogenesis mediated by type H endothelial cells (THECs). In this study, it is demonstrated that the Ilizarov technique induces the formation of a metaphysis‐like architecture composed of THECs, leading to segmental bone regeneration during the DO process. Mechanistically, cell‐matrix interactions‐mediated activation of yes‐associated protein (YAP)/transcriptional co‐activator with PDZ‐binding motif (TAZ) transcriptionally upregulates the expression of Notch1 and Delta‐like ligand 4, which act as direct positive regulators of THECs phenotype, in bone marrow endothelial cells (BMECs) upon TS stimulation. Simultaneously, the Notch intracellular domain enhances YAP/TAZ activity by transcriptionally upregulating YAP expression and stabilizing TAZ protein, thus establishing the YAP/TAZ‐Notch circuit. Additionally, TS‐stimulated BMECs secrete exosomes enriched with vital molecules in this positive feedback pathway, which can be utilized to promote segmental bone defect healing, mimicking the therapeutic effects of Ilizarov technique. The findings advance the understanding of TS‐induced segmental bone regeneration and establish the foundation for innovative biological therapeutic strategies aimed at activating THECs. Tensile stress‐induced activation of yes‐associated protein/transcriptional co‐activator with PDZ‐binding motif‐Notch positive feedback loop specifies type H endothelial cells (THEC) during distraction osteogenesis. Vital molecules involved in this circuit are enriched in exosomes for intercellular communication of regenerative signals, which can be further utilized to promote segmental bone regeneration through THEC activation, mimicking the therapeutic effects of the Ilizarov technique.

Bone lengthening and bone transport are regeneration processes that commonly rely on distraction osteogenesis, a widely accepted surgical procedure to deal with numerous bony pathologies. Despite the extensive study in the literature of the influence of biomechanical factors, a lack of knowledge about their mechanobiological differences prevents a clinical particularization. Bone lengthening treatments were performed on sheep metatarsus by reproducing the surgical and biomechanical protocol of previous bone transport experiments. Several in vivo monitoring techniques were employed to build an exhaustive comparison: gait analysis, radiographic and CT assessment, force measures through the fixation, or mechanical characterization of the new tissue. A significant initial loss of the bearing capacity, quantified by the ground reaction forces and the limb contact time with the ground, is suffered by the bone lengthening specimens. The potential effects of this anomaly on the musculoskeletal force distribution and the evolution of the bone callus elastic modulus over time are also analyzed. Imaging techniques also seem to reveal lower bone volume in the bone lengthening callus than in the bone transport one, but an equivalent mineralization rate. The simultaneous quantification of biological and mechanical parameters provides valuable information for the daily clinical routine and numerical tools development.