The knee meniscus: Structure–function, pathophysiology, current repair techniques, and prospects for regeneration

Abstract

Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee joint. As a vital part of the joint, it acts to prevent the deterioration and degeneration of articular cartilage, and the onset and development of osteoarthritis. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopedic and bioengineering communities. Current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus. Healing lesions found in the inner avascular region, which functions under a highly demanding mechanical environment, is considered to be a significant challenge. An adequate treatment approach has yet to be established, though many attempts have been undertaken. The current primary method for treatment is partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest towards the fields of biomaterials and bioengineering, where it is hoped that meniscal deterioration can be tackled with the help of tissue engineering. So far, different approaches and strategies have contributed to the in vitro generation of meniscus constructs, which are capable of restoring meniscal lesions to some extent, both functionally as well as anatomically. The selection of the appropriate cell source (autologous, allogeneic, or xenogeneic cells, or stem cells) is undoubtedly regarded as key to successful meniscal tissue engineering. Furthermore, a large variation of scaffolds for tissue engineering have been proposed and produced in experimental and clinical studies, although a few problems with these (e.g., byproducts of degradation, stress shielding) have shifted research interest towards new strategies (e.g., scaffoldless approaches, self-assembly). A large number of different chemical (e.g., TGF-β1, C-ABC) and mechanical stimuli (e.g., direct compression, hydrostatic pressure) have also been investigated, both in terms of encouraging functional tissue formation, as well as in differentiating stem cells. Even though the problems accompanying meniscus tissue engineering research are considerable, we are undoubtedly in the dawn of a new era, whereby recent advances in biology, engineering, and medicine are leading to the successful treatment of meniscal lesions.

Biological Augmentation and Tissue Engineering Approaches in Meniscus Surgery

“…Both the microarchitectural environment and biomechanical properties of a scaffold material act as biophysical cues for seeded and infiltrated cells. 13 In addition, the effect of mechanical loading on cellularized constructs, meniscus explants, and scaffoldless-assembly meniscus tissue is being investigated in an attempt to understand and use the resultant cellular responses; these may have a role in the maintenance of cell phenotype, matrix production, and overall improved vital role of cell phenotype maintenance and differentiation. Fibroblastic growth factor 2 has been shown to recover the monolayer expansion of meniscus cells, whereas TGF-ß1 has caused meniscus cells to take on a more chondrogenic phenotype.…”

“…Fibroblastic growth factor 2 has been shown to recover the monolayer expansion of meniscus cells, whereas TGF-ß1 has caused meniscus cells to take on a more chondrogenic phenotype. 13 As discussed, growth factor supplementation has shown improved cellular migration, proliferation, and matrix production, but important translational considerations include mode of delivery, localization of effect, and timing of growth factor release. The use of innovative imaging markers in future studies may prove efficacious in tracking cell migration and matrix production.…”

“…However, of critical importance is the understanding that current models of meniscus tissue engineering must also provide for the impact of mechanobiology (the effects of implant and tissue loading in the knee on cellular function and tissue formation). 13 This concept has grown in focus in recent years in the overall world of tissue engineering and regenerative medicine; it is of particular importance when considering musculoskeletal tissues. It may be of particular benefit to consider this in areas in which we have struggled in our efforts to make further advances toward the satisfactory surgical management of cartilage and meniscus lesions.…”

“…Hydrogels (natural or synthetic) are biochemically versatile and can be used as cell and growth factor delivery systems. 13 Although their biomechanical properties can be tailored somewhat by substrate concentration and composition, they often fall short of native meniscus properties. To overcome this problem, Holloway et al 51 proposed a fiber-reinforced composite containing ultra-high-molecular-weight polyethylene fibers in a polyvinyl alcohol hydrogel and varied the composition and orientation of the fibers to mimic native meniscus properties for total meniscus replacement.…”

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

“…In the laboratory, however, there are many studies investigating numerous scaffolds including chitosan, silk, collagen, alginate, polylactic acid, polygylcolic acid and polycaprolactone (PCL) (reviewed for the disc in Hudson et al, 2013;Kandel et al, 2008) and meniscus (Makris et al, 2011;Rongen et al, 2014;van Tienen et al, 2009). For both meniscus and intervertebral disc applications the addition of growth factors is also being studied.…”