Cell-Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath
Abstract
Topic Area: The proposed research will address the need to prevent the development of osteoarthritis after joint injuries that include meniscal injury. Background: The menisci, C-shaped fibrocartilage connective tissues located in the knee joint space, are critical to normal knee function by distributing compressive forces during knee joint movement. Over 1 million reported meniscal repair surgeries are performed in the United States annually. The majority of the injuries encountered are radial tears (often coincident with anterior cruciate ligament tears) involving the nonvascularized zone of the meniscus, a zone that has poor healing capacity. These types of injuries compromise the mechanical properties of the meniscus, which is designed to withstand both compressive and lateral stresses during movement. The consequence of these types of injuries is increased and abnormal forces within the knee that lead to cartilage degeneration and osteoarthritis (OA). The morbidity and cost of these injuries is high because these radial tears in the meniscus occur in young, active populations, such as athletes and military personnel. Current meniscus repair strategies fail due to either early mechanical overload of the surgical site and/or incomplete restoration of the native tissue structure and composition. Objective: The goal of this proposal is to develop a novel bio-activated, aligned, nanofibrous scaffold that will serve as mechanical and biological support for the repair of radial tears of the meniscus. The hypothesis is that scaffolds consisting of aligned polymeric fibers, which structurally and mechanically mimic tendon and fibrocartilage, may be applied as a patch in alignment with the fibers of the tissue to be repaired, i.e., the meniscus with radial tear, to strengthen mechanically the surgical meniscal repair, and to subsequently guide tissue regeneration, for example, by seeded tissue progenitor cells. Research Aims: To achieve this objective, the first step is to develop an aligned nanofibrous scaffold (NFS) that meets the mechanical requirements of the native meniscal matrix and provides suture retention. This will be done by combining nanofibers composed of Food and Drug Administration (FDA)-approved biodegradable polymers to produce a biocompatible scaffold, which will provide mechanical support to the healing meniscus. To support suture retention, a second layer of non-aligned fibers will be coated onto the aligned fibers. Second, the NFS will be bio-enhanced by impregnation with an extract derived from decellularized meniscus matrix, which contains molecules and growth factors specific to this tissue, to increase the formation of fibrocartilage by adult stem cells seeded within the scaffold. This bio-activation should enhance the biological integration, i.e., adhesion and tissue regenerating activity of the NFS in meniscus repair. Finally, we will test the ability of the bio-activated, aligned NFS sheath to enhance meniscus repair when combined with stem cell-based wound bonding strategies and standard suture repair using an in vitro model of meniscal repair (employed to elucidate the optimal combination of materials developed here) and in vivo, repairing surgically induced radial defects in a goat. Research Impact: It is recently reported that between 1998 and 2006, there were 100,201 acute meniscal injuries in the active military population -- a rate of 8.27 incidences per 1000 person years that is generally 10 times higher than in civilian populations. Eight-three percent of the affected individuals were under the age of 40 (median age 30 years). Over one-third of these patients will develop OA in the following 5-10 years, and the demands of military training may greatly increase this rate. In 2001, a study revealed that 50% of all Veterans with military service-connected injuries were treated for arthritic conditions and that the overall rate of arthritis treatment is 27% among all
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510104
Entities
People
- Rocky Tuan
Organizations
- United States Army
- University of Pittsburgh