Instructive materials for tendon and ligament augmentation

Tendons and ligaments (T/L) are the connective tissue that connect muscles to bone and bone to bone, respectively. The main function of tendons is to translate muscle contractions into join motion and consequently generate movement. Ligaments function to stabilize joints and guide them during their range of motion. Injuries in these tissues continue to be a major clinical problem for clinicians, patients and society in general. Additionally, the current treatment options fail to restore the biomechanical properties of the repaired tissue to those of the native tissue. The field of tissue engineering has been explored in order to improve the repair and healing of these damaged tissues with several studies being conducted that investigated the use of biomaterials, cells, bioactive factors or a combination of them. One of the most important bioactive molecules are the growth factors (GFs). These hormone-like proteins are involved in several cellular processes and play roles both in the development and repair of T/L. Although, use and administration of GFs is currently an engineering challenge, not clinically feasible and heavily regulated due to the side effects of their administration. In this thesis we present a non-covalent method for the delivery of GFs to promote and enhance the healing process of these tissues. This unique process uses GF binding peptides in order to achieve immobilization of hTGF-β1, hBMP-2 and hVEGF in different biomaterials. The immobilized GFs retained their bioactivity and elicited cell’s response in vitro and in vivo. The ultimate goal is to develop a sleeve functionalized with GF binding peptide, that can be wrapped around the damaged T/L or graft, in order to capture the endogenous GFs and present them to the damaged tissue. Spatial control over the presentation of different GFs on such sleeve will allow the enhancement of the healing of different tissues, such as bone, soft tissue and the interface between both.