Novel Approaches in Meniscal Repair Utilizing Mesenchymal Stem Cells, New Generation Bioscaffolds and Biological Adhesives as Cell Delivery Vehicles

Abstract

Mesenchymal stem cells (MSCs) have been widely applied in the repair of the knee-joint menisci which have a limited ability to undergo spontaneous repair. The menisci stabilise the knee-joint and are weight-bearing structures subjected to considerable tensional and compressive forces during flexion-extension and torsional loading of the knee. Traumatic loading of the knee-joint menisci can generate a number of lesions in the inner avascular meniscal regions. These have a limited capability of intrinsic repair and predispose the underlying articular cartilages to premature osteoarthritis. A number of strategies have therefore been developed for meniscal repair employing MSCs, bioscaffolds, hydrogels, biological glue cell delivery systems and agents which promote cell proliferation/matrix synthesis. Meniscal implants have also been developed in combination with the above procedures. It is important that meniscal defects be repaired not only to maintain kneejoint stability but also to prevent further degenerative changes in other knee joint tissues. Degenerative menisci contribute degradative proteinases and inflammatory mediators to the total synovial degradative proteinase pool. Partial or total surgical removal of the menisci is not a solution since this leads to premature osteoarthritis. Meniscal integrity needs to be maintained or repair strategies implemented in a timely manner to maintain knee joint function.

The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing Structures Providing Global Protection to Human Knee-Joint Tissues

“…MSCs have been sourced from bone marrow [95,97,98,99,100,101], adipose tissues [98,99,102,103] and synovium [62,94,98,103]. The utility of a number of bioscaffolds seeded with therapeutic cells have also been examined to promote repair of inner zone meniscal defects (reviewed in [18]). These scaffolds include a stem cell/collagen-derived scaffold [91], polyurethane [104] and a scaffold-free tissue-engineered construct derived from allogeneic synovial MSCs [98] besides a number of conventional tissue engineering synthetic resorbale bioscaffolds [105].…”

“…Knowledge of biological glues and tissue adhesives for the attachment of meniscal flaps or tears have undergone significant improvements in recent years. Tissue adhesives currently used in surgical applications, reviewed in [18,105] include the topical skin adhesive Dermabond ® (2-octyl cyanoacrylate), fibrin glue for pulmonary leaks, and the recently developed TissuGlu ® (an FDA approved urethane-based adhesive) for abdominoplasty surgery [116,117]. Tissue adhesives inspired by high performance adhesive marine compounds which firmly attach mussels [118] and barnacles [119] to marine substrates are promising tissue adhesives.…”

“…This is clearly evident in the focal localisation of the HS-proteoglycan perlecan which is a chondrogenic marker [10]. Figure modified from [18] with permission of InTech Open Publishers: London. Figure copyright J. Melrose.…”