The ultimate goal in the tissue engineering of the synovial joint is to fabricate biologically derived analogues that can replace severely degenerated or traumatized synovial joint components. A number of challenges must be addressed before reaching this ultimate goal. In this report, the relevance of cell seeding density in the synthesis of chondrogenic and osteogenic matrices from human mesenchymal stem cells is explored. Human mesenchymal stem cells (hMSCs) were differentiated into chondrogenic cells and osteogenic cells ex vivo and encapsulated in poly(ethylene glycol) diacrylate (PEGDA) hydrogel at densities of 5 x 106 cells/ml, 40 x 10(6) cells/ml, and 80 x 10(6) cells/ml, in addition to a cell-free poly(ethylene glycol) (PEG) control group (0 x 10(6) cells/ml). Cell-seeded or cell-free PEG constructs were separately incubated in vitro for 4 weeks or implanted in vivo in the dorsum of immunodeficient rats for 4 weeks. In-vitro data demonstrated that hMSC-derived chondrocytes or hMSC-derived osteoblasts maintained their lineages per Safranin O and von Kossa staining after incubation for 4 weeks. The general pattern of initial cell seeding densities of 5 x 10(6) cells/ml, 40 x 10(6) cells/ml, and 80 x 10(6) cells/ml were preserved following in-vitro cultivation. Similarly, in-vivo data revealed that hMSC-derived chondrocytes and hMSC-derived osteoblasts maintained their respective lineages and the pattern of cell-seeding densities. An attempt was made to fabricate a composite construct with PEGDA hydrogel and polycaprolactone (PCL) with designed internal porosity for an osteochondral graft. Various cell-seeding densities as delineated in this report can be realized in the composite PEG-PCL graft. The findings demonstrate that cell-seeding density is likely a key parameter to consider in tissue-engineering design. The source of cells can either be transplanted cells or internally recruited cells.

Synovial joints are created to enable movement among articulating bones. During movement, mechanical loading is transmitted across the joint, inducing mechanical stresses among all joint components such as articular cartilage, bone, meniscus, and ligaments. Articular cartilage plays critical roles in enabling motion in the synovial joint. Hyaline is the most common articular cartilage, whereas fibrocartilage is present in the semilunar meniscus of the knee, the temporomandibular joint of the jaw, and the intervertebral disk. The natural design of hyaline cartilage and fibrocartilage provides extraordinarily low friction and little wear under normal healthy conditions. However, molecular and ultrastructural structures of articular cartilage and meniscus can be destructed in diseases such as osteoarthritis and rheumatoid arthritis. For the purpose of this review, articular cartilage is discussed to represent hyaline cartilage, whereas knee meniscus is discussed as a representative of hyaline cartilage. Articular cartilage has a glassy appearance and consists of chondrocytes embedded in abundant, self‐made extracellular matrix (ECM). In contrast, knee meniscus consists of fibroblasts, chondrocytes, otherwise known as fibrochondrocytes, also embedded in self‐made ECM. Despite these superficial similarities, the composition of macromolecules in the ECM of articular cartilage and meniscus differs in important ways. Chondrocytes in articular cartilage primarily synthesize Type II collagen, whereas meniscus contains Type I and Type II collagens, likely synthesized by fibroblasts and chondrocytes separately or by fibrochondrocytes that express corresponding collagen genes. Collagen content and molecular weight in either articular cartilage or meniscus can be readily quantified. The second macromolecule in either articular cartilage or meniscus is proteoglycans. Highly negatively charged, large, and small proteoglycans retain water molecules and provide cartilage and meniscus with their resilience. From many of the studies that have formed the cornerstone of orthopedic medicine, it is known that collagen is chiefly responsible for the tensile strength of cartilage and meniscus, whereas proteoglycans provide compressive strength. Similarly, it should be recognized that collagen fibers and proteoglycan molecules cross‐anchor and function synergistically to enable walking, jogging, gymnastics, weightlifting, and innumerable physical activities human beings engage in. Rich literature exists of in‐depth characterization of articular cartilage and meniscus concerning their biology, biochemistry, and biomechanics. Observational and developmental biology studies have revealed not only the intricate compositions of articular cartilage and meniscus, but also molecular cues that regulate cellular function. For over a century, studies have explored the mechanical and physiochemical behaviors of these tissues under tension, compression, shear, hydrodynamic, and osmotic pressure loadings. Most of the sparse cells in adult articular cartilage are terminally differentiated chondrocytes engaged in matrix maintenance, rather than active chondroprogenitor cells capable of rapid proliferation. Evidently, the presence of angiogenesis favors bone formation from the same mesenchymal stem cells that, in the absence of vascularization, are capable of forming cartilage. Thus, the essential cause for the poor regenerative capacity of articular cartilage is not a lack of vascularization, but an intrinsic shortage of chondrogenic cells. Recent effort to tissue‐engineer articular cartilage and meniscus have used meritorious approaches such as stem cells or other tissue‐forming cells seeded in biocompatible porous‐permeable material scaffolds and growth factors. The novel concept of functional tissue engineering is an amalgamation of biologically based engineering approaches with physical stimulation toward the end goal of engineering a functionally adaptable articular cartilage and meniscus in vivo . This chapter will provide synthesis of the literature on biomechanical properties of articular cartilage and meniscus, and a brief update of current tissue engineering efforts to create synovial joint condyle and knee meniscus with an eventual goal toward the replacement of these diseased structures, for example, in osteoarthritis.

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