Tissue Engineering of Ligaments

The main function of a ligament is to connect one bone to another bone across a joint, keeping them aligned to prevent abnormal motions and dislocations. The typical magnitude of force a ligament may experience during day-to-day activities varies. For example the anterior cruciate ligament of the knee can be exposed to daily tensile forces ranging between 67N for ascending stairs to 630N for jogging (Vunjak-Novakovic, Altman et al. 2004), whereas large loads, exceeding 1800N, can cause rupturing. Depending upon anatomical location and the extent of vascularisation, the ligament may or may not be capable of selfhealing after a rupture. Some of the most frequently ruptured ligaments occur in the knee joint, often through sporting activities such as skiing, football and basketball and the number of injuries are increasing each year (Cooper, Lu et al. 2005). Ninety percent of knee ligament injuries involve the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) (Woo, Abramowitch et al. 2006). The MCL can self-heal, but the ACL cannot due to poor vascularisation. Because of this, alternative methods such as regenerative medicine have focused heavily upon the ACL with the aim of producing a fully functional tissue in vitro. Figures indicate that approximately 250,000 people are diagnosed with ACL injuries each year in the USA (Doroski and Brink 2007), and approximately 150,000 need to undergo surgical treatment, known as an ACL reconstruction (Cooper, Lu et al. 2005). If the rupture is not treated it can cause loss of function of the associated joint which can then lead to early development of osteoarthritis (Cooper and Bailey 2006; Gentleman, Livesay et al. 2006). The current gold standard procedure for an ACL reconstruction is surgical autografting. This involves using part of the patients own patellar tendon, hamstring or quadriceps to replace the ruptured ACL (Beasley, Weiland et al. 2005). However, these techniques cause donor site morbidity (Goulet and Germain 1997; Van Eijk, Saris et al. 2004; Cooper and Bailey 2006; Hairfield-Stein, England et al. 2007) which is associated with pain and a recovery period for the donor tissue site (Cooper, Lu et al. 2005; Hairfield-Stein, England et al. 2007). Generally 75-90% of patients have good or excellent long term success rates from these current grafting techniques (regarding functional stability and symptomatic relief upon return to normal activities) but unfortunately a substantial number of patients exist who have unsatisfactory results which could be attributed to graft failure (Vergis and Gillquist 1995). Some of these patients continue to endure pain, suffer from loss of motion secondary to the operative procedure and continue with recurrent instability (Vergis and Gillquist 1995), while others suffer from degenerative joint disease such as arthritis or