Regeneration of whole meniscus using meniscal cells and polymer scaffolds in a rabbit total meniscectomy model

Abstract

The current treatments of meniscal lesion in knee joint are not perfect to prevent adverse effects of meniscus injury. Tissue engineering of meniscus using meniscal cells and polymer scaffolds could be an alternative option to treat meniscus injury. This study reports on the regeneration of whole medial meniscus in a rabbit total meniscectomy model using the tissue engineering technique. Biodegradable scaffolds in a meniscal shape were fabricated from polyglycolic acid (PGA) fiber meshes that were mechanically reinforced by bonding PGA fibers at cross points with 75:25 poly(lactic-co-glycolic acid). The compressive modulus of the bonded PGA scaffold was 28-fold higher than that of nonbonded scaffold. Allogeneic meniscal cells were isolated from rabbit meniscus biopsy and cultured in vitro. The expanded meniscal cells were seeded onto the polymer scaffolds, cultured in vitro for 1 week, and transplanted to rabbit knee joints from which medial menisci were removed. Ten or 36 weeks after transplantation, the implants formed neomenisci with the original scaffold shape maintained approximately. Hematoxylin and eosin staining of the sections of the neomenisci at 6 and 10 weeks revealed the regeneration of fibrocartilage. Safranin-O staining showed that abundant proteoglycan was present in the neomenisci at 10 weeks. Masson's trichrome staining indicated the presence of collagen. Immunohistochemical analysis showed that the presence of type I and II collagen in neomenisci at 10 weeks was similar to that of normal meniscal tissue. Biochemical and biomechanical analyses of the tissue-engineered menisci at 36 weeks were performed to determine the quality of the tissue-engineered menisci. Tissue-engineered meniscus showed differences in collagen content and aggregate modulus in comparison with native meniscus. This study demonstrates, for the first time, the feasibility of regenerating whole meniscal cartilage in a rabbit total meniscectomy model using the tissue engineering method.

Dynamic compressive loading of image-guided tissue engineered meniscal constructs

“…While there have been improvements in suturing techniques and devices to repair focal lesions (Farng and Sherman, 2004), no options exist for whole meniscal replacement other than cadaveric allografts. To this end, tissue engineering techniques have been used in efforts to replicate the complex shape of the meniscus and generate constructs that can mimic biochemical and mechanical properties of native tissue (Ballyns et al, 2008, 20010a;Gunja et al, 2009;Kang et al, 2006).…”

In vitro engineering of fibrocartilage using CDMP1 induced dermal fibroblasts and polyglycolide

“…Moreover, for the tissue engineering approach, a scaffold is a key issue for delivery of seed cells and provides a suitable spatial template for tissue growth in a 3-D arrangement. As one of the most commonly used synthetic polymers in cartilage tissue engineering, PGA has been shown to possess good biocompatibility and suitable biodegradation rate both in vitro [20,28] and in vivo [4,29]. To maintain its dimensional stability and enhance its mechanical properties, fibrous PGA meshes are always treated with PLA solution.…”

“…A variety of cell sources have been applied as seed cells for engineering fibrocartilage. Because of the donor sites morbidity for harvesting, low expansion and synthetic capacity during dedifferentiation and aging when cultured in vitro, chondrocytes isolated from either hyaline cartilage or fibrocartilage is not a good candidate in fibrocartilage engineering [3][4][5]. Bone marrow derived mesenchymal stem cells (BMSCs) have been used to treat fibrocartilage defects in a rabbit model [6].…”

“…The 3-D microenvironment offered by biodegradable PGA scaffold rather than a 2-D monolayer culture system was chosen due to the fact that it could allow more cell-matrix and cell-cell contact which is usually required for the enhanced chondrogenic differentiation of seeded cells [18]. Moreover, PGA scaffold has been successfully applied to support the growth of articular and meniscal chondrocytes, and to engineer fibrocartilage in vitro [4]. The proliferation and synthesis of glycosaminoglycan (GAG) by DFs in the presence of CDMP1 in vitro was investigated in detail.…”

Application of cell and biomaterial-based tissue engineering methods in the treatment of cartilage, menisci and ligament injuries

“…Kang et al [105] reported the regeneration of rabbit menisci using the PGA/PLGA scaffold seeded with allogenic meniscal cells implanted into the knee joint. At the 10th week, meniscal regeneration was observed and collagen and PG content in the newly-formed tissue was similar to that of native tissue.…”