Development of a Hierarchical Electrospun Scaffold for Ligament Replacement

The anterior cruciate ligament (ACL) is a dense collagenous structure that connects the femur to the tibia and is vital for joint stability. The ACL possesses complex time-dependent viscoelastic properties and functions primarily to prevent excessive translations and rotations of the tibia relative to the femur. It is estimated that 400,000 ACL tears occur in the United States annually and the monetary burden of these injuries and their subsequent treatment is approximately $1 billion annually. After injury allografts and autografts are commonly implanted to reconstruct the torn ACL in an attempt to restore joint stability, prevent pain, and limit damage to surrounding tissues. However surgical reconstructions fail to completely restore knee functionality or prevent additional injury and regardless of intervention technique radiographic osteoarthritis is present in 13% of patients 10 years after ACL rupture.

Drawbacks to traditional treatments for ACL ruptures motivate the development of a synthetic ACL replacement. Tissue engineering is the use of a scaffold, cells, and signaling molecules to create a replacement for damaged tissue. The goal of this work is to develop a polymer scaffold that can be utilized as a replacement for the ACL. A tissue engineered ACL replacement should replicate the hierarchical structure of the native ACL, possess reasonable time zero mechanical properties, and promote the deposition of de novo collagenous tissue in vitro. Additionally, the scaffold should be implantable using standard surgical techniques and should maintain in situ tibiofemoral contact mechanics. Thus, four specific aims are proposed:

Fabricate and characterize an aligned 3-dimensional electrospun scaffold for ACL replacement.

Assess the in vitro behavior of ovine bone marrow-derived stems cells seeded on the scaffold in the presence of conjugated growth factor.

Evaluate the performance of the electrospun scaffold using uniaxial mechanical testing.

Assess the effect of the electrospun scaffold on ovine stifle joint contact mechanics.

Development of a tissue engineered ACL replacement that mimics the structure and function of the native ACL would provide a novel treatment to improve outcomes of ACL injuries.

Keywords:

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Year

Entry

2005

Discher DE, Janmey P, Wang Y-l. Tissue cells feel and respond to the stiffness of their substrate. Science. November 18, 2005;310(5751):1139-1143.

2001

Provenzano P, Lakes R, Keenan T, Vanderby R Jr. Nonlinear ligament viscoelasticity. Ann Biomed Eng. October 2001;29(10):908-914.

1992

Butler DL, Guan Y, Kay MD, Cummings JF, Feder SM, Levy MS. Location-dependent variations in the material properties of the anterior cruciate ligament. J Biomech. May 1992;25(5):511-518.

2007

Nerurkar NL, Elliott DM, Mauck RL. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res. August 2007;25(8):1018-1028.

1978

Kastelic J, Galeski A, Baer E. The multicomposite structure of tendon. Connect Tissue Res. 1978;6(1):11-23.