Current concept
Tissue Engineering for Anterior Cruciate Ligament Reconstruction: A Review of Current Strategies

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Abstract

The anterior cruciate ligament (ACL) is one the most commonly injured ligaments of the knee. Chronic ACL insufficiency can result in episodic instability, chondral and meniscal injury, and early osteoarthritis. The intra-articular environment of the ligament precludes normal healing and surgical replacement of the injured ligament is often mandated to restore stability. Current surgical strategies include the use of local autograft or allograft tissues for ligament reconstruction. These procedures have yielded superior long-term clinical results yet have the potential for serious associated morbidities. Existing limitations have prompted ongoing research designed to engineer a replacement ligament that will parallel the native ACL in both its biologic properties and mechanical durability. Ligament engineering necessitates the use of appropriate source cells and a growth matrix to support cell proliferation and collagen synthesis. The identification of appropriate growth modulators including both biochemical factors and mechanical stimuli are requisites for successful tissue growth. The characterization of the elements essential for successful graft development represents a significant challenge for investigators. This review examines the current literature regarding the potential and limitations of ligament engineering and describes the development of a novel 3-dimensional scaffold and bioreactor system at our institution.

Section snippets

Ligament healing

An appreciation of the physiology underlying ligament healing is necessary to efficiently formulate a system for ex vivo ligament engineering. In many extra-articular ligaments, such as the medial collateral ligament (MCL), healing occurs in 3 phases: hemostasis and inflammation, cellular proliferation and matrix deposition, and long-term remodeling.27, 28, 29 During the initial 72 hours following ligament injury, a hematoma develops within the soft tissue surrounding the ligament. This area is

Ligament engineering

The development of a functional engineered ligament is predicated on a system that uses (1) reparative cells with the capacity for proliferation and matrix synthesis, (2) a structural scaffold that facilitates cell adaptation, and (3) an environment that provides sufficient nutrient transport and appropriate regulatory stimuli (Fig 1). These constituents may be applied in either an in vivo or ex vivo system. In vivo ligament engineering uses a scaffold that is designed to be implanted into the

The UCLA experience

The aforementioned investigations represent the foundation of knowledge of ligament engineering. Collectively, the data suggest that fibroblasts and mesenchymal stem cells can be cultured on natural and synthetic ligament scaffolds, and that these cells respond to a number of biochemical and mechanical stimuli by proliferation, differentiation, and elaboration of ECM. However, the goal of synthesizing a functional ligament, or simply a tissue that can withstand biomechanical testing, has yet to

Summary

The current strategies applied to ACL reconstruction are satisfactory. However, the goal of improving this procedure and eliminating its associated complications is a practical one. With the heightened emphasis on fitness and athleticism in the United States, the prevalence of ACL injuries will likely continue to rise. A suitable tissue-engineered ACL replacement may obviate many of the current shortcomings of current autograft and allograft techniques, while allowing patients to promptly

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