Tissue-Engineering Strategies for Ligament Reconstruction
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MRS BULLETIN/NOVEMBER 1996
Our laboratory is developing a similar approach for ligament reconstruction. Ligaments are the strong, flexible bands of collagenous tissue that connect boneto-bone to provide a delicate balance of stability and flexibility to the joints of the body. The anterior cruciate ligament (ACL) is the primary stabilizer of the knee and is frequently injured in sporting activities and accidents. Serious ACL injuries can lead to disability and progressive degeneration of cartilage and meniscus that normally serve as shock absorbers in the joint. Anterior-cruciateligament ruptures do not heal without surgical intervention, due to a poor intrinsic healing response and poor vascularity. To restore normal joint function, ruptured ACLs can be surgically reconstructed using a patellar-tendon autograft or allograft. While significant progress has been made in understanding ACL anatomy, structure, biomechanics, and healing, there is still no biological graft or biomaterial ideally suited for ACL reconstruction.1"3 This article focuses on the tissue-engineering approach to ligament reconstruction and identifies critical issues in the use of scaffolds, cells, and signals to repair or regenerate ligaments and other musculoskeletal soft tissues. Resorbable Scaffolds for Ligament Reconstruction Ligaments are complex composite materials that can be modeled as continuous fibers aligned in parallel within a deformable matrix. Scaffolds for ligament reconstruction are typically biomimetic, with a similar composite design. The fiber and matrix biomaterials can be natural or synthetic but must satisfy strict design
criteria including biocompatibility, high initial strength and modulus, and a moderate resorption rate to gradually transfer mechanical loads to ingrowing neoligament tissue. As in all engineering designs, there are tradeoffs involved in optimizing scaffold performance. It is difficult if not impossible to satisfy all the design criteria. In general, currently available synthetic materials are deficient with respect to tissue interactions. For natural materials, the mechanical properties and resorption rates are difficult to consistently control. We have investigated scaffolds containing both natural (collagen) and synthetic fibers and matrices for ACL reconstruction. Collagen Fibers Collagen is a triple helical protein that self-assembles into strong, ropelike fibers that provide mechanical stability to all tissues of the body. Collagen has numerous biological functions and serves as the natural scaffold, supporting cell attachment, proliferation, and matrix synthesis within the body. Because of these unique mechanical and biological properties, collagen has been used extensively as a biomaterial in various physical forms including solution, powder, sponge, film, and fiber. Collagen fibers (50-100-/j.m diameter) for ACL reconstruction scaffolds are made by extruding a 1% (weight/volume) acid-insoluble bovine dermal collagen dispersion into saline solution, rinsing, and drying under tension. Fibers are c
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