In Vitro Induction of Hypertrophic Chondrocyte Differentiation of Naïve MSCs by Strain.

In the context of bone fractures, the influence of the mechanical environment on the healing outcome is widely accepted, while its influence at the cellular level is still poorly understood. This study explores the influence of mechanical load on naïve mesenchymal stem cell (MSC) differentiation, focusing on hypertrophic chondrocyte differentiation. Unlike primary bone healing, which involves the direct differentiation of MSCs into bone-forming cells, endochondral ossification uses an intermediate cartilage template that remodels into bone.

Assessment of Intraoperative Scoring Systems for Predicting Cytoreduction Outcome in Peritoneal Metastatic Disease: A Systematic Review and Meta-analysis.

Background: Cytoreductive surgery (CRS) is a widely acknowledged treatment approach for peritoneal metastasis, showing favorable prognosis and long-term survival. Intraoperative scoring systems quantify tumoral burden before CRS and may predict complete cytoreduction (CC). This study reviews the intraoperative scoring systems for predicting CC and optimal cytoreduction (OC) and evaluates the predictive performance of the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV).

A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition.

Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice.

Limbostomy: Longitudinal Intravital Microendoscopy in Murine Osteotomies.

Bone healing involves the interplay of immune cells, mesenchymal cells, and vasculature over the time course of regeneration. Approaches to quantify the spatiotemporal aspects of bone healing at cellular resolution during long bone healing do not yet exist. Here, a novel technique termed Limbostomy is presented, which combines intravital microendoscopy with an osteotomy.

Genetic variation in mice affects closed femoral fracture pattern outcomes.

The purpose of this study was to determine whether differences in structural and material properties of bone between different mouse strains influence the fracture patterns produced under experimental fracture conditions. Femurs of C57BL/6 (B6), C3H/HeJ (C3H), and DBA/2 (DBA) strains were evaluated using micro-computed tomography (μCT), measurements derived from radiographic images and mechanical testing to determine differences in the geometry and mechanical properties. A fracture device was used to create femoral fractures on freshly sacrificed animals using a range of kinetic energies (∼20-80mJ) which were classified as transverse, oblique, or comminuted.

In Vivo Evaluation of Fracture Callus Development During Bone Healing in Mice Using an MRI-compatible Osteosynthesis Device for the Mouse Femur.

Endochondral fracture healing is a complex process involving the development of fibrous, cartilaginous, and osseous tissue in the fracture callus. The amount of the different tissues in the callus provides important information on the fracture healing progress. Available in vivo techniques to longitudinally monitor the callus tissue development in preclinical fracture-healing studies using small animals include digital radiography and µCT imaging.

Longitudinal intravital imaging of the femoral bone marrow reveals plasticity within marrow vasculature.

The bone marrow is a central organ of the immune system, which hosts complex interactions of bone and immune compartments critical for hematopoiesis, immunological memory, and bone regeneration. Although these processes take place over months, most existing imaging techniques allow us to follow snapshots of only a few hours, at subcellular resolution. Here, we develop a microendoscopic multi-photon imaging approach called LIMB (longitudinal intravital imaging of the bone marrow) to analyze cellular dynamics within the deep marrow.

Reamed locked intramedullary nailing for studying femur fracture and its complications.

Morbidity associated with femur fractures in polytrauma patients is known to be high. The many unsolved clinical questions include the immunological effect of the fracture and its fixation, timing of fracture fixation, management of fracture non-union, effect of infection and critical size of bone defects. The aim of this study was to establish a clinically-relevant and reproducible animal model with regards to histological, biomechanical and radiological changes during bone healing.

Characterization of interfragmentary motion associated with common osteosynthesis devices for rat fracture healing studies.

Rat models are widely used in preclinical studies investigating fracture healing. The interfragmentary movement at a fracture site is critical to the course of healing and therefore demands definition in order to aptly interpret the experimental results. Estimation of this movement requires knowledge of the fixation stiffness and loading.

Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice.

Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (μCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus.

An Intramedullary Locking Nail for Standardized Fixation of Femur Osteotomies to Analyze Normal and Defective Bone Healing in Mice.

Bone healing models are essential to the development of new therapeutic strategies for clinical fracture treatment. Furthermore, mouse models are becoming more commonly used in trauma research. They offer a large number of mutant strains and antibodies for the analysis of the molecular mechanisms behind the highly differentiated process of bone healing.

Biomechanical comparison of pin and tension-band wire fixation with a prototype locking plate fixation in a transverse canine patellar fracture model.

Objective: To compare a locking plate (LP) with pin and tension-band wire (pin/TBW) for fixation of mid-patellar transverse fractures.

Materials And Methods: Cadaveric canine stifle joints from 10 adult mixed breed dogs (23-36 kg) were used. Mid-patellar transverse osteotomies were randomly stabilized (in pairs) with either pin/TBW or a prototype LP.

End caps prevent nail migration in elastic stable intramedullary nailing in paediatric femoral fractures: a biomechanical study using synthetic and cadaveric bones.

End caps are intended to prevent nail migration (push-out) in elastic stable intramedullary nailing. The aim of this study was to investigate the force at failure with and without end caps, and whether different insertion angles of nails and end caps would alter that force at failure. Simulated oblique fractures of the diaphysis were created in 15 artificial paediatric femurs.

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models.

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal.

A standardized critical size defect model in normal and osteoporotic rats to evaluate bone tissue engineered constructs.

Tissue engineered constructs should be tested for their efficacy not only in normal but also in osteoporotic bone. The rat is an established animal model for osteoporosis and is used often for bone healing studies. In this study a defined and standardized critical size defect model in the rat suitable for screening new tissue engineered constructs in normal and osteoporotic bone is described and validated.

Rodent animal models of delayed bone healing and non-union formation: a comprehensive review.

Despite the growing knowledge on the mechanisms of fracture healing, delayed healing and non-union formation remain a major clinical challenge. Animal models are needed to study the complex process of normal and impaired fracture healing and to develop new therapeutic strategies. Whereas in the past mainly large animals have been used to study normal and impaired fracture healing, nowadays rodent models are of increasing interest.

A novel murine femoral segmental critical-sized defect model stabilized by plate osteosynthesis for bone tissue engineering purposes.

Mouse models are invaluable tools for mechanistic and efficacy studies of the healing process of large bone defects resulting in atrophic nonunions, a severe medical problem and a financial health-care-related burden. Models of atrophic nonunions are usually achieved by providing a highly stable biomechanical environment. For this purpose, external fixators have been investigated, but plate osteosynthesis, despite its high clinical relevance, has not yet been considered in mice.

Establishment of a femoral critical-size bone defect model in immunodeficient mice.

Background: The development of innovative therapies for bone regeneration requires the use of advanced site-specific bone defect small-animal models. The achievement of proper fixation with a murine model is challenging due to the small dimensions of the murine femur. The aim of this investigation was to find the optimal defect size for a murine critical-size bone defect model using external fixation method.

A new model to analyze metaphyseal bone healing in mice.

Background: Despite the increasing clinical problems with metaphyseal fractures, most experimental studies investigate the healing of diaphyseal fractures. Although the mouse would be the preferable species to study the molecular and genetic aspects of metaphyseal fracture healing, a murine model does not exist yet. Using a special locking plate system, we herein introduce a new model, which allows the analysis of metaphyseal bone healing in mice.

Design, characterisation and in vivo testing of a new, adjustable stiffness, external fixator for the rat femur.

Very little is known about the influence of the mechanical environment on the healing of large segmental defects. This partly reflects the lack of standardised, well characterised technologies to enable such studies. Here we report the design, construction and characterisation of a novel external fixator for use in conjunction with rat femoral defects.

Plunging when drilling: effect of using blunt drill bits.

Objective: Plunging when drilling can be a detrimental factor in patient care. There is, although, a general lack of information regarding the surgeon's performance in this skill. The aim of this study was to determine the effect that using sharp or blunt instruments had on the drill bit's soft tissue penetration, using a simulator.

Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting.

Small animal fracture models have gained increasing interest in fracture healing studies. To achieve standardized and defined study conditions, various variables must be carefully controlled when designing fracture healing experiments in mice or rats. The strain, age and sex of the animals may influence the process of fracture healing.

Sildenafil accelerates fracture healing in mice.

Sildenafil, a cyclic guanosine monophosphate (cGMP)-dependent phospodiesterase-5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro-angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture.

Melatonin impairs fracture healing by suppressing RANKL-mediated bone remodeling.

Background: Melatonin, the major pineal hormone, is known to regulate distinct physiologic processes. Previous studies have suggested that it supports skeletal growth and bone formation, most probably by inhibiting bone resorption. There is no information, however, whether melatonin affects fracture healing.

Fracture healing in mice under controlled rigid and flexible conditions using an adjustable external fixator.

Mice are increasingly used to investigate mechanobiology in fracture healing. The need exists for standardized models allowing for adjustment of the mechanical conditions in the fracture gap. We introduced such a model using rigid and flexible external fixators with considerably different stiffness (axial stiffnesses of 18.