26 research outputs found
Micromechanical study of the load transfer in a polycaprolactone-collagen hybrid scaffold when subjected to unconfined and confined compression
Scaffolds are used in diverse tissue engineering applications as hosts for cell proliferation and extracellular matrix formation. One of the most used tissue engineering materials is collagen, which is well known to be a natural biomaterial, also frequently used as cell substrate, given its natural abundance and intrinsic biocompatibility. This study aims to evaluate how the macroscopic biomechanical stimuli applied on a construct made of polycaprolactone scaffold embedded in a collagen substrate translate into microscopic stimuli at the cell level. Eight poro-hyperelastic finite element models of 3D printed hybrid scaffolds from the same batch were created, along with an equivalent model of the idealized geometry of that scaffold. When applying an 8% confined compression at the macroscopic level, local fluid flow of up to 20Â [Formula: see text]m/s and octahedral strain levels mostly under 20% were calculated in the collagen substrate. Conversely unconfined compression induced fluid flow of up to 10Â [Formula: see text]m/s and octahedral strain from 10 to 35%. No relevant differences were found amongst the scaffold-specific models. Following the mechanoregulation theory based on Prendergast et al. (J Biomech 30:539-548, 1997. https://doi.org/10.1016/S0021-9290(96)00140-6 ), those results suggest that mainly cartilage or fibrous tissue formation would be expected to occur under unconfined or confined compression, respectively. This in silico study helps to quantify the microscopic stimuli that are present within the collagen substrate and that will affect cell response under in vitro bioreactor mechanical stimulation or even after implantation
Identification of Mechanosensitive Genes during Embryonic Bone Formation
Although it is known that mechanical forces are needed for normal bone
development, the current understanding of how biophysical stimuli are
interpreted by and integrated with genetic regulatory mechanisms is limited.
Mechanical forces are thought to be mediated in cells by
âmechanosensitiveâ genes, but it is a challenge to
demonstrate that the genetic regulation of the biological system is dependant on
particular mechanical forces in vivo. We propose a new means of selecting
candidate mechanosensitive genes by comparing in vivo gene expression patterns
with patterns of biophysical stimuli, computed using finite element analysis. In
this study, finite element analyses of the avian embryonic limb were performed
using anatomically realistic rudiment and muscle morphologies, and patterns of
biophysical stimuli were compared with the expression patterns of four candidate
mechanosensitive genes integral to bone development. The expression patterns of
two genes, Collagen X (ColX) and Indian hedgehog (Ihh), were shown to colocalise
with biophysical stimuli induced by embryonic muscle contractions, identifying
them as potentially being involved in the mechanoregulation of bone formation.
An altered mechanical environment was induced in the embryonic chick, where a
neuromuscular blocking agent was administered in ovo to modify skeletal muscle
contractions. Finite element analyses predicted dramatic changes in levels and
patterns of biophysical stimuli, and a number of immobilised specimens exhibited
differences in ColX and Ihh expression. The results obtained indicate that
computationally derived patterns of biophysical stimuli can be used to inform a
directed search for genes that may play a mechanoregulatory role in particular
in vivo events or processes. Furthermore, the experimental data demonstrate that
ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators
in translating information from the mechanical environment to the molecular
regulation of bone formation in the embryo
Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis
Tissue differentiation in an in vivo bioreactor: in silico investigations of scaffold stiffness
Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells
Modelling the course of healing of a long bone subjected to loading has been the subject of several investigations. These have succeeded in predicting the differentiation of tissues in the callus in response to a static mechanical load and the diffusion of biological factors. In this paper an approach is presented which includes both mechanoregulation of tissue differentiation and the diffusion and proliferation of cell populations (mesenchymal stem cells, fibroblasts, chondrocytes, and osteoblasts). This is achieved in a three-dimensional poroelastic finite element model which, being poroelastic, can model the effect of the frequency of dynamic loading. Given the number of parameters involved in the simulation, a parameter variation study is reported, and final parameters are selected based on comparison with an in vivo experiment. The model predicts that asymmetric loading creates an asymmetric distribution of tissues in the callus, but only for high bending moments. Furthermore the frequency of loading is predicted to have an effect. In conclusion, a numerical algorithm is presented incorporating both mechanoregulation and evolution of cell populations, and it proves capable of predicting realistic difference in bone healing in a 3D fracture callus.Precision and Microsystems EngineeringMechanical, Maritime and Materials Engineerin