Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1503, MSC 8022, Bethesda, MD 20892-8022, USA.
Functional engineering of musculoskeletal tissues generally involves the use of differentiated or progenitor cells seeded with specific growth factors in biomaterial scaffolds. Ideally, the scaffold should be a functional and structural biomimetic of the native extracellular matrix and support multiple tissue morphogenesis. We have previously shown that electrospun, three-dimensional nanofibrous scaffolds that morphologically resemble collagen fibrils are capable of promoting favorable biological responses from seeded cells, indicative of their potential application for tissue engineering. In this study, we tested a three-dimensional nanofibrous scaffold fabricated from poly(epsilon-caprolactone) (PCL) for its ability to support and maintain multilineage differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in vitro. hMSCs were seeded onto pre-fabricated nanofibrous scaffolds, and were induced to differentiate along adipogenic, chondrogenic, or osteogenic lineages by culturing in specific differentiation media. Histological and scanning electron microscopy observations, gene expression analysis, and immunohistochemical detection of lineage-specific marker molecules confirmed the formation of three-dimensional constructs containing cells differentiated into the specified cell types. These results suggest that the PCL-based nanofibrous scaffold is a promising candidate scaffold for cell-based, multiphasic tissue engineering.
"During the cell fate determination process, stem cells sense and react to physical properties of their microenvironment. Accordingly , some cell fates are reached only in three-dimensional (3-D) cell cultures  . To date, in spite of extensive research efforts to control stem cell differentiation, the efficiency achieved in lineagerestricted differentiation is often poor. "
"MSCs are a heterogeneous population of plastic-adherent, fibroblast-like cells, from which the progenitor cells in culture are able to self-renew and differentiate into multiple lineages  . Recent studies showed that combining human MSCs and biomaterials with controlled properties, or by adding certain growth factors, differentiation towards chondrogenic  , osteogenic  , myogenic , adipogenic   endothelial , and neurogenic  lineage can be achieved. Distribution and adherence of cells in scaffolds play a crucial role in the efficiency of tissue engineering approaches. "
"In this study, the scaffolds used have both a polymer phase and a ceramic phase. As mentioned earlier, PLGA scaffolds release acidic degradation products, which may cause inflammatory responses in vivo (Li et al., 2005). The lactic and glycolic acidosis created within the engineered tissue may promote cell hypertrophy. "
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