Second Generation of Tissue-Engineered Ligament Substitutes for Torn ACL Replacement: Adaptations for Clinical Applications

The anterior cruciate ligament (ACL) of the knee joint is one of the strongest ligaments of the body and is often the target of traumatic injuries. Unfortunately, its healing potential is limited, and the surgical options for its replacement are frequently associated with clinical issues. A bioengineered ACL (bACL) was developed using a collagen matrix, seeded with autologous cells and successfully grafted and integrated into goat knee joints. We hypothesize that, in order to reduce the cost and simplify the model, an acellular bACL can be used as a substitute for a torn ACL, and bone plugs can be replaced by endobuttons to fix the bACL in situ. First, acellular bACLs were successfully grafted in the goat model with 18% recovery of ultimate tensile strength 6 months after implantation (94 N/mm2 vs. 520). Second, a bACL with endobuttons was produced and tested in an exvivo bovine knee model. The natural collagen scaffold of the bACL contributes to supporting host cell migration, growth and differentiation in situ post-implantation. Bone plugs were replaced by endobuttons to design a second generation of bACLs that offer more versatility as biocompatible grafts for torn ACL replacement in humans. A robust collagen bACL will allow solving therapeutic issues currently encountered by orthopedic surgeons such as donor-site morbidity, graft failure and post-traumatic osteoarthritis.

Mechanical Characteristics of Tissue Engineered Bone-Ligament-Bone Constructs Following ACL Replacement in Sheep

With approximately 400,000 reported each year, anterior crucial ligament (ACL) injuries are the most common injury in the US. Unfortunately current ACL replacement strategies, which involve using either allografts from cadavers or autografts from patients’ own patellar tendons (PT) or hamstring tendons as a replacement, have several limitations including graft availability, risk of rejection, increased morbidity and, more importantly, unmatched intra-articular biomechanical properties of grafts and ACL. The objective of this study is to use self-assembling, scaffold-less bone-ligament-bone (BLB) engineered tissue constructs as grafts in a sheep ACL repair model to characterize the biomechanical behaviors of native ACL, PT, and tissue engineered ligament and subsequently present a viable option of using tissue engineered ligament graft for ACL repair.

Non-Linear Viscoelastic Mechanics of Native and Engineered Ligaments and Tendons

Patellar tendon (PT) autografts and allografts are the most common methods currently used to replace a torn anterior cruciate ligament (ACL). The PT is not only much stiffer than the ACL it replaces it also exhibits qualitatively and quantitatively different non-linear viscoelastic behavior from those of the ACL. These mis-matched biomechanics may be contributing to the high incidence of early onset osteoarthritis suffered by patients who have had ACL surgeries. Thus there is a need for an ACL graft that can reproduce normal ligament biomechanics and knee function. This talk examines the inhomogeneous, non-linear viscoelastic response of native ACL and of a tissue engineered ACL graft designed to rapidly grow and remodel in vivo to restore the proper biomechanical properties of native ligament. The results using this graft as an ACL replacement are compared against those using a PT autograft for the ACL replacement. Uniaxial loading reveals that after nine months as an ACL replacement, the tissue-engineered graft develops a strain contour pattern closely resembling that of native ACL whereas the PT graft fails to similarly remodel in vivo.