Novel Perfused Compression Bioreactor System as an in vitro Model to Investigate Fracture Healing
نویسندگان
چکیده
Secondary bone fracture healing is a physiological process that leads to functional tissue regeneration via endochondral bone formation. In vivo studies have demonstrated that early mobilization and the application of mechanical loads enhances the process of fracture healing. However, the influence of specific mechanical stimuli and particular effects during specific phases of fracture healing remain to be elucidated. In this work, we have developed and provided proof-of-concept of an in vitro human organotypic model of physiological loading of a cartilage callus, based on a novel perfused compression bioreactor (PCB) system. We then used the fracture callus model to investigate the regulatory role of dynamic mechanical loading. Our findings provide a proof-of-principle that dynamic mechanical loading applied by the PCB can enhance the maturation process of mesenchymal stromal cells toward late hypertrophic chondrocytes and the mineralization of the deposited extracellular matrix. The PCB provides a promising tool to study fracture healing and for the in vitro assessment of alternative fracture treatments based on engineered tissue grafts or pharmaceutical compounds, allowing for the reduction of animal experiments.
منابع مشابه
The development of a novel model of direct fracture healing in the rat
OBJECTIVES Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. METHODS A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley...
متن کاملIn Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System.
Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dy...
متن کاملNew Insight on Deformation of Walnut/Ceramic Proppant Pack under Closure Stress in Hydraulic Fracture: Numerical Investigation
This study is an attempt to investigate the mechanical behavior of proppant packs deforming under compression loading. A generalized confined compression test (CCT) was simulated in the present study to investigate the deformation of walnut/ceramic proppants against compression. In this way, the CCT was simulated using ABAQUS explicit code. Unlike ordinary CCT, we obtained permeability of compr...
متن کاملElastic cartilage grafting in canine radial fracture
Bone has a capability to repair itself when it is fractured. Repair involves the generation of intermediatetissues, such as fibrous connective tissue, cartilage and woven bone, before final bone healing can occur. Theprocess of cartilage-to-bone transition (CBT) is a key for the achievement of rigid bone healing duringfracture repair. We tested this potential for elastic cartilage using a long ...
متن کاملA Novel Integrated Approach to Modelling of Depletion-Induced Change in Full Permeability Tensor of Naturally Fractured Reservoirs
More than half of all hydrocarbon reservoirs are Naturally Fractured Reservoirs (NFRs), in which production forecasting is a complicated function of fluid flow in a fracture-matrix system. Modelling of fluid flow in NFRs is challenging due to formation heterogeneity and anisotropy. Stress sensitivity and depletion effect on already-complex reservoir permeability add to the sophistication. Horiz...
متن کامل