Outlook for Tissue Engineering Strategies for Anterior Cruciate Ligament Reconstruction

Introduction

Anterior cruciate ligament (ACL) rupture is a common injury of the knee. Limitations of allografts and autografts in ACL reconstruction as well as recent advancements in biology and materials science have spurred interest in developing tissue-engineered ACL replacements that have the potential to mimic the native ACL in terms of both biological and mechanical properties. This chapter reviews current strategies that surround the development of a tissue-engineered ACL substitute and explores the limitations as well as future direction of these technologies. The four basic components of tissue engineering, biomaterial scaffolds, cell sources, growth factors, and mechanical stimuli, will be addressed. In addition, animal models that have been used to evaluate these tissue-engineered ACL replacements will also be reviewed.

ACL reconstruction is a common surgical procedure that is necessary because of the inherent inability of a ruptured ACL to heal. Current treatment consists of reconstruction with autograft or allograft rather than primary repair. While autografts have been successfully employed, the chief drawback is donor site morbidity, which can result in pain, infrapatellar contracture, tendonitis, weakness, and patella fracture. Additionally, in multiligamentous knee injury, recurrent injury, or revision surgery, autograft may be unavailable. The use of allograft can circumvent most of the these issues, but can be associated with limited supply, delayed biological incorporation, and the risk of disease transmission. Also, allografts are associated with a higher re-rupture rate, particularly in younger, more active patients.

Due to these limitations, there has been interest in developing synthetic ACL substitutes since the early 1970s. Nonbiodegradable synthetic grafts such as Proplast, Dacron, and GORE-TEX have all been previously evaluated for ACL reconstruction. While these grafts had sufficient initial strength, all had complications with particulate wear debris, the associated synovitis, and ultimately graft failure. Currently, there are no synthetic replacements for primary ACL reconstruction approved for clinical use in the United States.

Recent advances in biology and materials science have prompted researchers to develop a tissue-engineered ligament substitute. Tissue engineering is a multidisciplinary field that incorporates principles of engineering, biology, and materials science to replace or regenerate tissues in order to restore normal function. This field was popularized by Langer and Vacanti in the late 1980s, and operates under the paradigm of four basic components: a structural scaffold, a cell source, biologic modulators, and mechanical modulators. In orthopaedics, tissue engineering techniques have been applied to developing therapies for cartilage loss and bony nonunion, as well as tendon and ligament insufficiency. The ACL’s unique mechanical properties and inability to heal are the major challenges that have limited the development of tissue-engineered solutions to ACL rupture.