In the article, Current tissue engineering strategies in anterior cruciate ligament reconstruction, Leong, Petrigliano, and McAllister (2013) review the available literature on this topic. The tearing of the anterior cruciate ligament (ACL) ranks amongst the most prevalent causes of ligament injury. The correction of the ACL tear requires surgery, which involves the use of autografts, but this strategy raised issues surrounding the harvest of the autografts and the effects on the patient coupled with rerupture rates. Scientists shifted focus to synthetic grafts, but they also posed numerous challenges, which forced the Food and Drug Administration (FDA) to withdraw them from the market.
In the absence of any synthetic ACL replacement in the market, scientists moved to tissue engineering in a bid to come up with tissue-engineered ligament grafts. However, the tissue-engineered approaches to ACL tears are hindered given the complex properties of the ligament and its incapability to heal after a rupture due to its intraarticular positioning. Therefore, given the aforementioned challenges, scientists started focusing on medial collateral ligament (MCL), which is placed at the extraarticular and thus it heals easily after a tear, in a bid to relate the healing procedure to ACL. Unfortunately, these ligaments have different mechanical properties and thus drawing a positive correlation between the two healing processes posed a challenge.
Nevertheless, scientists have come up with ways of studying the ACL tear healing process by adopting different strategies. The first one is the use of biomaterial scaffolds. This approach appeared to work but it faced numerous in-vitro challenges including decreasing tensile strength and reabsorption of collagen, which was used as a scaffold. However, silk-collagen scaffolds were found to have over 25% matching properties with the native ACL, and FDA has already approved the use of synthetic biodegradable silk-collagen polymers.
The choice of cell sources underscores the other approach to ACL substitutes via tissue engineering. Ligament fibroblasts are the preferred choice for ligament regeneration, but they occur in small amounts in addition to having poor proliferation properties. However, stem cell technology now facilitates the use of multipotent and pluripotent stem cells. The choice of cell sources for ACL tear reconstruction is thus a key aspect as the right cells assist in multidimensional aspects in the regenerative process. Growth factors also play a key role in ACL regeneration as they influence different properties in the regenerative process. Most growth factors influence mitosis, which is a key aspect in ACL regeneration and thus they play an important role in tissue engineering. Mechanical conditioning is another important aspect in ACL tissue engineering. The knee has to withstand different forces and the mechanical properties of its constituents are critical elements. Mechanical strain has been shown to stimulate cell growth, but more research is needed to ascertain such findings in vivo.
Finally, animal studies play a key role in the study of tissue-engineered ACL grafts in vitro. However, the FDA’s numerous regulation on the use of large animals in research trials has been an impediment to this process. Therefore, scientists have come up with disparate animal models for the research. Tissue engineering has been a success in small animals and to some extent in larger animals. However, given the quadrupeds nature of animals, the challenge has been how to replicate that in humans, as they are bipedal. Despite the numerous efforts to come up with ACL grafts, so far scientists have not come up with a successful graft to be used in humans. This assertion underscores the dire need to continue with the tissue-engineering research on ACL grafts.
Reference
Leong, N., Petrigliano, F., & McAllister, D. (2013). Current tissue engineering strategies in anterior cruciate ligament reconstruction. Journal of Biomedical Materials Research, 102(5), 1614-1624.