There is a constant rise in demand for artificial meniscal grafts mimicking native articular tissue to be used for surgical treatment of meniscal lesions. In Europe alone over 400,000 surgical cases involving the meniscus are being performed annually, and over 1 million similar cases are treated in the United States. By far meniscectomy is known to be the most common surgical procedure performed in the orthopedic field today. The current therapeutic strategy for this type of meniscus tears is either partial or subtotal meniscectomy, with only a small percentage being successfully repaired but finally leading to osteoarthritis of the knee with time (Fairbank, 1948; Englund et al., 2003).
A functional intact meniscus is of paramount importance for homeostasis of the knee joint. It helps perform complex knee joint biomechanics, in load bearing, load transmission, shock absorption, joint stability and joint lubrication. However, due to lack of vasculature, human meniscus has a poor healing potential. Blood vessels are reported to be present only in the outer 10-30% of the meniscal body and can be sutured successfully with a high success rate (Englund et al., 2003; Buma et al., 2004). In contrast, majority of these meniscal tears are situated in the inner avascular zone lacking spontaneous healing process and hence be resected (Kohn et al., 1999). Removal and/or damage of all this important anatomical structure eventually leads to degenerative changes of the articular cartilage, osteoarthritis and subsequent clinical symptoms due to increased peak stresses (Fairbank, 1948; Cole et al., 2003; Chatain et al., 2003; Englund et al., 2003). It has been estimated that cartilage volume loss after meniscectomy is at 4% per year and is known to be more pronounced in the lateral compartment as compared to medial compartment (Verdonk and Kohn, 1999).
To this problem, meniscus allo/autograft transplantation represents a potential tissue engineering solution for the symptomatic, meniscus deficient patient to substitute for lost meniscal tissue to prevent cartilage degeneration, relieve pain and to improve function. The strategies included delivery of potent cells to the defect site for repair including chondrocytes, fibrochondrocytes and stem cells (Peretti et al., 2004; Izuta et al., 2005; Port et al., 1996). The other strategy being direct replacement of defective tissue in part or as a whole has also been carried out using both natural and synthetic scaffolds, including collagen-based grafts, subintestinal submucusa, cell free hydrogels, degradable porous foams, macro- and microporous polymeric meshes to improve immediate or long term outcomes (Buma et al., 2004; Stone et al., 1992; Cook et al., 2006 a; Setton et al., 1999; Sweigart et al., 2001; Kobayashi et al., 2005; Kelly et al., 2007; Van Tienen et al., 2002; Heijkants et al., 2004; Cook et al., 2006 (a, b). In the past, a variety of these materials have already been reported for cartilage tissue engineering including, poly-glycolic acid (PGA), poly-L-lactic acid (PLA), copolymer poly-lactic-co-glycolic acid (PLGA) and alginate (Grande et al., 1997; Freed et al., 1993 a,b; Paige et al., 1996; Marijnissen et al., 2002; Ma et al., 2003). However, these materials have intrinsic limitations, including inflammation in vivo in the case of the polyesters and rapid degradation and high swelling in the case of collagen, which can limit their use (Cancedda et al., 2003; Athanasiou et al., 1996; Wakitani et al., 1994; Meinel et al., 2004 a,b). In terms of meniscus shape, a PGA spun matrix was used in a rabbit model but failed to recapitulate the complex internal meniscus architecture (Kang et al., 2006). Additional efforts have focused on mimicking the native mesh-like meniscus architecture using cell alignment on biodegradable electrospun fibers for enhanced biomechanics (Baker and Mauck; 2007; Baker et al., 2009). Many of the above studies employed in vivo animal models to show chondroprotection by the implant, but with a low success rate due to failure to mimic the complex internal architecture and biomechanics of the native meniscus.
In order to develop a functional tissue engineered meniscus, mimicking its complex internal architecture is most important. In this regard, none of the approaches previously reported have successfully recapitulated the complex native meniscal multiporous and aligned structure as a single meniscus wedge shaped unit to completely and/or partially eliminate cartilage degeneration. Thus, in order to mimic the meniscus in a tissue engineered approach, understanding its structural and functional components is important. Menisci are wedge-shaped semi-lunar discs present in duplicate in each knee joint which are attached to the transverse ligaments, the joint capsule, the medial collateral ligament (medially) and the menisco-femoral ligament (laterally) (McDevitt and Webber, 1990; Sweigart and Athanasiou, 2001). An extensive scanning electron micrograph study of the human meniscus by Peterson and Tillmann showed 3 distinct zones comprising of outer finer meshwork, middle broader mesh like fibrous structure and bottom most aligned collagen bundles in laminar orientation (Petersen and Tillmann, 1998). This particular aligned laminar orientation of fibers along with mesh structure within was reported to contribute maximally for its high intrinsic tensile and compressive properties of native meniscus (Sweigart and Athanasiou, 2001; Tissakht and Ahmed, 1995; Petersen and Tillmann, 1998). As a fibrocartilaginous structure, the meniscus has characteristic of both fibrous (outer region) and cartilaginous (inner region) properties (O'Connor, 1976; Petersen and Tillmann, 1998). Knee meniscal fibrocartilaginous tissue contains mainly water (72%), collagens (22%) and glycosaminoglycans (0.8%) (Proctor et al, 1989; Herwig et al, 1984). Of the total collagen content, Type I collagen accounts for over 90%. The remaining 10% are meniscal collagens Type II, III and V collagen (Eyre and Wu, 1983; McDevitt and Webber, 1990). It has been shown that peripheral two-thirds of the meniscus solely consist of type I collagen, whereas type II collagen comprises a large portion of the fibrillar collagen on the inner side (Cheung, 1987). Proteoglycans make for 2-3% of the dry weight and are mainly concentrated in the inner cartilaginous region of the meniscus (McDevitt and Webber, 1990; Buma et al., 2004). Also, the cellular component of the meniscus further reflects its fibrocartilaginous nature, the main cell type being meniscus fibrochondrocytes (McDevitt and Webber, 1990). Regarding cell types, at least two cell populations are present within the human meniscus (Ghadially et al., 1983). The fibrochondrocytes being the main cell type are reported within the inner and middle part of the meniscus having a rounded or oval shaped cell structure surrounded by an abundant ECM deposition (McDevitt and Webber, 1990; Ghadially et al., 1983). The outer one-third meniscus is reported to be populated mainly by spindle shaped fibroblast like cells with a dense connective tissue (Ghadially et al., 1983).
Over the years, newer improvised methods such as meniscus allograft or autograft transplantation have been constantly searched for substituting the resected meniscus in case of either total or partial meniscectomy. However, none to date have generally been able to recapitulate and recreate the native meniscal multiporous and aligned structure as a single meniscus wedge shaped unit to completely and/or partially eliminate cartilage regeneration. As such, there is still a strong need to develop a scaffold that can mimic heterogeneous architecture and functions of native meniscal tissue.