A Computational Model of Osteochondral Defect Repair Following Implantation of Stem Cell-Laden Multiphase Scaffolds.

Developing successful tissue engineering strategies requires an understanding of how cells within an implanted scaffold interact with the host environment. The objective of this study was to use a computational mechanobiological model to explore how the design of a cell-laden scaffold influences the spatial formation of cartilage and bone within an osteochondral defect. Tissue differentiation was predicted using a previously developed model, in which cell fate depends on the local oxygen tension and the mechanical environment within a damaged joint.

Mechanical Testing of Cartilage Constructs.

A key goal of functional cartilage tissue engineering is to develop constructs with mechanical properties approaching those of the native tissue. Herein we describe a number of tests to characterize the mechanical properties of tissue engineered cartilage. Specifically, methods to determine the equilibrium confined compressive (or aggregate) modulus, the equilibrium unconfined compressive (or Young's) modulus, and the dynamic modulus of tissue engineered cartilaginous constructs are described.

Substrate stiffness and oxygen availability as regulators of mesenchymal stem cell differentiation within a mechanically loaded bone chamber.

Mechanical stimuli such as tissue deformation and fluid flow are often implicated as regulators of mesenchymal stem cell (MSC) differentiation during regenerative events in vivo. However, in vitro studies have identified several other physical and biochemical environmental cues, such as substrate stiffness and oxygen availability, as key regulators of stem cell fate. Hypotheses for how MSC differentiation is regulated in vivo can be either corroborated or rejected based on the ability of in silico models to accurately predict spatial and temporal patterns of tissue differentiation observed experimentally.

Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions.

A therapy for regenerating large cartilaginous lesions within the articular surface of osteoarthritic joints remains elusive. While tissue engineering strategies such as matrix-assisted autologous chondrocyte implantation can be used in the repair of focal cartilage defects, extending such approaches to the treatment of osteoarthritis will require a number of scientific and technical challenges to be overcome. These include the identification of an abundant source of chondroprogenitor cells that maintain their chondrogenic capacity in disease, as well as the development of novel approaches to engineer scalable cartilaginous grafts that could be used to resurface large areas of damaged joints.

Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model.

Extrinsic mechanical signals have been implicated as key regulators of mesenchymal stem cell (MSC) differentiation. It has been possible to test different hypotheses for mechano-regulated MSC differentiation by attempting to simulate regenerative events such as bone fracture repair, where repeatable spatial and temporal patterns of tissue differentiation occur. More recently, in vitro studies have identified other environmental cues such as substrate stiffness and oxygen tension as key regulators of MSC differentiation; however it remains unclear if and how such cues determine stem cell fate in vivo.

Simulation of a balloon expandable stent in a realistic coronary artery-Determination of the optimum modelling strategy.

Computational models of stent deployment in arteries have been widely used to shed light on various aspects of stent design and optimisation. In this context, modelling of balloon expandable stents has proved challenging due to the complex mechanics of balloon-stent interaction and the difficulties involved in creating folded balloon geometries. In this study, a method to create a folded balloon model is presented and utilised to numerically model the accurate deployment of a stent in a realistic geometry of an atherosclerotic human coronary artery.

Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells.

Articular cartilage has a poor intrinsic capacity for self-repair. The advent of autologous chondrocyte implantation has provided a feasible method to treat cartilage defects. However, the associated drawbacks with the isolation and expansion of chondrocytes from autologous tissue has prompted research into alternative cell sources such as mesenchymal stem cells (MSCs) which have been found to exist in the bone marrow as well as other joint tissues such as the infrapatellar fat pad (IFP), synovium and within the synovial fluid itself.

The influence of plaque composition on underlying arterial wall stress during stent expansion: the case for lesion-specific stents.

Intracoronary stent implantation is a mechanical procedure, the success of which depends to a large degree on the mechanical properties of each vessel component involved and the pressure applied to the balloon. Little is known about the influence of plaque composition on arterial overstretching and the subsequent injury to the vessel wall following stenting. An idealised finite element model was developed to investigate the influence of both plaque types (hypercellular, hypocellular and calcified) and stent inflation pressures (9, 12 and 15 atm) on vessel and plaque stresses during the implantation of a balloon expandable coronary stent into an idealised stenosed artery.