A coupled finite element - analytical model is presented to predict and to elucidate a clinical healing scenario where bone regenerates in a critical-sized femoral defect, bounded by periosteum or a periosteum substitute implant and stabilised via an intramedullary nail. Bone regeneration and maintenance processes are intrinsically linked to mechanical environment. However, the cellular and subcellular mechanisms of mechanically-modulated bone (re-) generation are not fully understood. Recent studies with periosteum osteoprogenitor cells exhibit their mechanosensitivity Summary Statement
Introduction
Flow chambers have been implemented in stem cell research to apply controlled dilational (volume changing) and deviatoric (shape changing) mechanical cues to living cells. Studies implementing such chambers demonstrate that controlled delivery of mechanical cues correlates strongly to changes in stem cell shape, structure, and fate. A custom designed flow chamber, capable of delivering highly controlled stresses at the cellular scale, enables the study of flow-induced normal and shear stresses on cell behavior. Specifically, computational fluid dynamics (CFD) and multiphysics modeling (coupling of CFD with finite element models) allow for controlled delivery of mechanical cues via fluid flow and cell seeding protocols, concomitant to optical mapping of cell displacements due to mechanical load, and calculation of flow velocities, imbued stresses, and cellular strains within a given volume of interest. Akin to conducting a mechanical loading test on single cells and groups of cells, paired experimental and computational experiments using the custom-designed chamber enabled calculation of the flow field's effect on the cell(s) as well as the cells’ effect on the flow field, a critical step in predicting the local stress and strain fields at the cell-fluid interface within the chamber, during exposure to fluid flow. These stresses-strains experienced by stem cells demonstrate significant correlation to cell gene expression, and strongly suggest that stresses at the cell-fluid interface influence cell fate. The current study uses a parametric approach to define next steps to prospectively guide mechanically-modulated lineage commitment.Summary Statement
Introduction
Progenitor cells from the periosteal niche are of great clinical interest due to their remarkable regenerative capacity. Here we report on progenitor cells from arthritic patients whose femoral neck periosteum was resected over the course of hip replacement. This study aims to determine whether periosteum derived cells (PDCs) can be isolated from tissue resected in the normal course of hip arthroplasty. Further, it aims to determine how different isolation protocols affect PDC behavior (surface marker expression, proliferation, and differentiation). In addition, the study aims to characterise the populations of PDCs, isolated through either enzymatic digestion or migration, and their relative capacity to differentiate down multiple capacities; direct comparison with commercially available human marrow-derived stromal cells cultured under identical conditions will enable the placement of the PDC data in context of the current state of the field.Summary Statement
Introduction
The purpose of this experimental imaging study is to determine the Poisson's ratio of ovine periosteum, using strain mapping data from an imaging study designed to elucidate the mechanical environment of periosteal progenitor cells Periosteum is a composite, so-called “smart” or stimuli responsive material that provides a niche for pluripotent cells that exhibit mechanosensitivity in their proliferative and differentiation behavior. The overarching aim of this research program is to explore, understand, and exploit the mechanical signals that promote cell lineage commitment and Summary Statement
Introduction
Thickness and cellularity of human periosteum are important parameters both for engineering replacement tissue as well as for surgeons looking to minimise tissue damage while harvesting the most viable periosteum possible for autologous regenerative therapies. This study provides a new foundation for understanding the basic structural features of middiaphyseal periosteum from femora and tibiae of aged donors. A number of recent studies describe mechanical, permeability and regenerative properties of periosteal tissue and periosteum derived cells in a variety of animal models [1,2]. However, due to lack of access in healthy patients, the structural properties underlying human periosteum's inherent regenerative power and advanced material properties are not well understood. Periosteum comprises a cellular cambium layer directly apposing the outer surface of bone and an outer fibrous layer encompassed by the surrounding soft tissues. As a first step to elucidate periosteum's structural and cellular characteristics in human bone, the current study aims to measure cambium and fibrous layer thickness as well as cambium cellularity in human femora and tibiae of aged donors.Summary Statement
Introduction
The purpose of this study was to examine the effects of cement-free implant fixation on microperfusion in the vicinity of the bone-implant interface and to elucidate the effects of mechanical loading on interstitial fluid flow. Experiments were conducted on both forelimbs of sheep (n=8, age: 4–7 years) using an ex vivo model. Immediately after euthanasia, forelimbs were amputated and a system of perfusion with Procion red (0,08 %) as flow indicator was established. In one group (4 animals), an prosthesis was inserted into the reamed intramedullary cavity of the metacarpus. In a second group (4 animals) no implant was inserted. For each pair, one limb (chosen randomly) was subjected to cyclic loading. Loading was applied at a rate of 1 Hz for 5 minutes. Infusion lasted 5 minutes in all limbs. After the experiment histological cross sections were taken and analysed for the amount of tracer present. Twelve regions were marked on the slide prior to examination and acquired under fluorescence mode. The average pixel intensity of each field of view, was measured using ‘Scion Image’ software. The mean (± standard deviation) of the 12 readings (pixel intensities) for each group were as follows: Non-implanted group, loaded: 83.31 (± 13.56); Non-implanted group, unloaded 80.80 (± 9.22); Implanted group, loaded: 71.86 (± 19.28); Implanted group, unloaded 66.79 (± 15.52). Anova analysis showed the effect of loading not to be significant statistically (p = 0.082) but the effect of implant to be highly significant (p0.0001). Implant fixation and mechanical loading affect both microperfusion and interstitial fluid flow modulated mass transport in bony tissue surrounding implants. It appears that the presence of an implant per se reduces perfusion as well as fluid flow in the vicinity of the bone-implant interface. Within subchondral bone loading does not have a significant effect on transport of small molecular weight tracers.
