Mechanical conditioning of cell-seeded constructs for soft tissue repair - Are optimisation strategies possible?

Abstract

Tissue Engineering is a major focus of biotechnological research today, with the expectation that this type of technique will ultimately transform medical practice (Nerem, 2000). The most ambitious tissue engineering schemes assume that specific tissues and organs will be restored, in a multi stage fabrication procedure. For example, cells derived from the patient may be processed to increase the total number available, seeded into a suitable three-dimensional resorbable scaffold and the resultant construct may be further processed in vitro using specially designed bioreactor systems to induce the elaboration of neo-tissue prior to implantation (Bader and Lee, 2000). The importance of mechanical stimulation in maintaining the integrity of healthy load-bearing soft tissues is widely accepted, both for metabolism and homeostasis. As an example, during normal activity, the articular cartilage of the major load bearing joints is exposed to complex loading, which is predominantly compressive in nature. It is well known that this mechanical environment is essential for the lubrication and nutrition of chondrocytes embedded in the extracellular matrix (ECM) of this avascular tissue. Previous studies have reported that static compression of explanted cartilage causes a down-regulation of matrix synthesis, while cyclic compression may induce an up-regulation of matrix synthesis dependent on the dynamic frequency applied (Sah et al., 1989; Kim et al., 1994). Accordingly, the manner in which cells respond to different mechanical environments has attracted a wide interest, with studies investigating the role of various intracellular signalling pathways associated with mechanotransduction. In addition, there are an increasing number of authors who have proposed in vitro mechanical conditioning strategies for cell-seeded scaffolds as an essential feature for the long term functionality of tissue engineered implants. This requires the development of suitable bioreactors, incorporating mechanical loading modules for use in a controlled biological environment. These are designed to provide appropriate mechanical conditioning regimes recognised to stimulate the formation of a functional neo-tissue, thereby improving the efficacy and efficiency of production of tissue engineered implants. In order to successfully develop and optimise bioreactor systems for mechanical conditioning of cell-seeded constructs, it is necessary to understand the complex interplay between the nature of the loading regime applied, the scaffold material and the cells seeded within the scaffold. This chapter describes studies conducted by the authors and others, aimed at developing mechanical loading strategies for use in functional tissue engineering of soft tissue defects. These studies primarily address issues related to the nature of the loading regimes adopted, the sourcing of cells for tissue engineering and the nature of the scaffold material. © 2005 Springer.