Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects

Abstract

Cartilage defects that penetrate the subchondral bone can undergo spontaneous repair through the formation of a fibrous or cartilaginous tissue mediated primarily by mesenchymal stem cells from the bone marrow. This tissue is biomechanically inferior to normal articular cartilage, and is often observed to degrade over time. The factors that control the type and quality of the repair tissue, and its subsequent degradation, have yet to be elucidated. In this paper, we hypothesise a relationship between the mechanical environment of mesenchymal stem cells and their subsequent dispersal, proliferation, differentiation and death. The mechano-regulation stimulus is hypothesised to be a function of strain and fluid flow; these quantities are calculated using a finite element model of the tissue. A finite element model of an osteochondral defect in the knee was created, and used to simulate the spontaneous repair process.

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

“…Using this mechano-regulation model (Prendergast et al, 1997), it has been possible to predict the spatial and temporal patterns of tissue differentiation during a number of regenerative events such as fracture healing Nagel and Kelly 2009), osteochondral defect repair (Kelly and Prendergast 2005;Kelly and Prendergast 2006) and distraction osteogenesis (Boccaccio et al, 2007;Boccaccio et al, 2008). However even with the use of complex computational models, it is difficult to determine how specific mechanical signals influence MSC differentiation in vivo within the milieu of other regulatory factors that are present.…”

The Influence of Expansion Rates on Mandibular Distraction Osteogenesis: A Computational Analysis

“…As cells disperse throughout the repair tissue, they 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 6 are hypothesized to differentiate depending on the magnitude of a biophysical stimulus. Following previous work 19,23,25,36 , the biophysical stimulus for tissue differentiation is taken to be a function of the octahedral shear strain γ and interstitial fluid flow ν in the extracellular environment of the cells according to:…”

“…The temporal change in E i , the Young's Modulus for tissue phenotype i (where i is fibrous tissue, cartilage or immature or mature bone), was described using the following equation: 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 to the values utilized in previous studies 23,25 (E fibrous = 2 MPa; E cartilage = 10 MPa; E immature bone = 1000…”

“…bulk solid modulus, permeability etc. ), as scant information is available on their evolution in time during the tissue differentiation process, it was assumed that these material properties changed based only on the rule of mixtures as used in other studies 23,25 .…”

“…This model was used to successfully predict the patterns of tissue differentiation during fracture healing 25 , at implant/bone interfaces 2,19 and during osteochondral defect repair. 23 In 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 this study, this same model will be further developed in order to investigate mandibular distraction osteogenesis, and in particular, to perform a computational mechanobiological analysis on the rate of expansion of the device. Four different protocols of expansion will be investigated: the first one where the device is distracted by 0.6mm/day for a period of ten days, the second where the device is distracted at 1.2 mm/day for five days, the third where the device is distracted by 2mm/day for three days and the fourth where the device is distracted by 3mm/day for two days.…”