Tissue Engineering for Anterior Cruciate Ligament and Rotator Cuff Tendon Repair

A major research area for the Arruda group is the tissue engineering of soft tissues and their interfaces. One of the major challenges in soft tissue engineering of tissues such as muscle, ligament and tendon is the attachment of the engineered tissue to native tissue. In our approach we engineer the tissue interfaces in vitro to provide a structurally viable and biochemically relevant interface at the time the tissue is implanted. A current paradigm in soft tissue engineering is that the mechanical properties of the engineered tissue must match those of the native tissue it is replacing at the time it is implanted. Methods that have used this design paradigm have failed to thrive in vivo, often losing mechanical integrity (stiffness and strength) during the first few weeks and months after implantation. Our approach recognizes that a critical mechanical property that has not been given proper scrutiny in ligament tissue engineering is extensibility, and as long as the engineered tissue can stretch during knee motion, it will not break. This is because ligaments are not loaded by specific weights like the bones of the skeleton. Ligaments must deform to allow movement of joints.

A specific example of what we’re doing is tissue engineering of a bone/ligament/bone construct for use as knee ligament replacement or reconstruction. Anterior cruciate ligament (ACL) reconstruction surgeries using tendon grafts are performed in the US at a rate of nearly 300,000 per year. In addition to the high economic costs associated with knee surgery (6B/yr), acute knee injury is a risk factor for osteoarthritis (OA). Limitations associated with grafting including availability, donor site morbidity, immune rejection, degradation of mechanical properties and incomplete ligamentization, have led investigators to develop strategies to engineer ligament tissue. Current methodologies for engineering ligament using scaffolds suffer similar limitations including immune rejection, degradation, non-physiological intra-articular mechanical properties and incomplete attachment to the bone tunnel. To more closely replicate native intra-articular ligament and promote integration with native bone within the bone tunnel, a multi-phasic engineered ligament with engineered bone at each end and a mechanically viable and biochemically relevant interface between the two tissues would be optimal for replacement. To address this need, our laboratory has developed a scaffold-less method using bone marrow stromal cells (BMSCs) to engineer an in vitro multi-phasic ligament model or bone-ligament-bone (BLB) construct that exhibits the structural and functional interface characteristics of young native tissue. We have demonstrated that our BLB constructs rapidly grow and remodel in vivo to an advanced phenotype, develop a vascular (blood) supply and nerves and physically, mechanically, and biochemically closely resemble the native tissue they have replaced.

Another example application is repair of the supraspinatus tendon of the rotator cuff. This tendon attaches one of the muscles of the rotator cuff to the humerus, providing stability to the shoulder. When torn, the current repair paradigm is to suture it to the humerus. This procedure often results in scarring, pain, and a loss of range of motion. In our laboratory we use a bone-tendon graft to repair the torn tendon. We have preliminary data demonstrating favorable outcomes compared to suture repair.