Engineering soft/hard tissue interfaces

Ligament and tendon injuries are relatively commonplace in patients of all age groups. These connective tissues enable joint locomotion and their injury can result in a debilitating loss of joint function and consequently a significant reduction in a patient's quality of life. Currently, ligament damage is repaired either by using a synthetic material to replace ligament function or by using tissue that is often harvested from elsewhere in the patients body (often from the hamstring or the quadriceps tendon). Failure of these repairs usually occur as a consequence of tensile stress concentrations at the interface with bone (enthesis) that can result in ligament detachment. In normally functioning ligaments, the interface with bone is specially structured with four continuous and yet distinct regions which protect the attachment point by ensuring that it is subject principally to compressive loads. In this work, we will seek to reproduce this structure by interfacing a tissue engineered ligament with a calcium phosphate based anchor material in a bioreactor system. The adhesion of the ligament to the ceramic structure will allow the mechanical conditioning of the tissue outside the body. By providing the necessary mechanical and chemical stimuli to a population of mesenchymal stem cells within the ligament, it may be possible to recreate the specialised enthesis structure in vitro. Ultimately, it is hoped that this multi-component tissue engineered structure will form an intimate bond with bone, resulting in the eventual regeneration of the ligament and enthesis in vivo leading to a better long term clinical outcome for the patient.

Although many approaches have been applied clinically in the repair and augmentation of diseased and damaged bone, there are currently major issues associated with the repair of the soft/hard tissue interface. Such interfaces are essential for joint articulation and hence locomotion and a loss of their integrity can result in a significant reduction in the patient's quality of life. The anterior cruciate ligament, for example, may be repaired by mechanical fixation, the clinical success of this approach, however, is limited by poor fixation at the graft-bone junction the friability of which is the primary cause of graft failure. Failure typically occurs at the graft-bone junction as a result of localised stress concentrations at the interface between the tendon/ligament and bone, which are caused by a mismatch in modulus between the tissues of several orders of magnitude. In vivo, these stress concentrations are avoided by a complex fibrocartilaginous interfacial region (enthesis) that effectively transfers the load between the more and less compliant tissues. The proposed work will seek to produce a multi-tissue construct using a novel method for engineering a ligament-like structure in vitro, which will interface with a calcium phosphate based bracket of defined morphology. Ultimately, it is anticipated that this approach will allow us to engineer replacement ligaments and tendons in vitro for eventual implantation and clinical treatment of ligament/tendon damage.