[Show abstract][Hide abstract] ABSTRACT: Osteochondral lesions are often seen in orthopedics, but the available treatment strategies are limited in success. Regenerative medicine provides novel concepts for curing them. The purpose of this study was to test the effects of perfusion and cyclic compression on cell differentiation and mechanical properties using a custom-made biomechanoreactor in a recently established system of human bone marrow stromal cells (hBMSC) cultured in a 3-D collagen I-bone hybrid matrix out of commercially available and separately in human-certified products. Seeded hBMSC were viable for 88 +/- 8.9% during the entire experimental period in the constructs. GAG and DNA levels did not change. Perfusion induced collagen II and cyclic compression increased collagen X expression. Matrix stiffness was significantly increased after 28 days of cyclic compression. Cyclic compression of cell-loaded hybrid constructs enhanced chondrocyte differentiation and matrix stiffness. This system is a promising tool with a view to a later clinical application.
[Show abstract][Hide abstract] ABSTRACT: A tissue-engineered articular condyle could provide a new alternative approach to joint replacement. This study describes progress made towards engineering an articular condyle in vitro using human bone marrow stromal cells (hBMSCs) in a biphasic matrix. hBMSCs were transferred to a rat collagen-I hydrogel which was then pressed onto a bovine cancellous bone matrix. The gel/cell suspensions, each at a density of approximately 5 x 10(5)cells/ml containing fourth passage cells pressed into an adult human tibial condyle form using CT scan based moulds. The osteochondral constructs fabricated in vitro were stimulated in a bioreactor using cyclic compression and continuous perfusion. Penetration and cell distribution were demonstrated as homogeneous and cells were found to be viable after gel compression. The filamentous structure of the collagen fibres was more dense and homogeneous using compression. Mechanical tests showed a significant enhancement of primary matrix stability after initial compression. Stiffness was not observed to increase significantly over 7 days under loading in a bioreactor. The successful integration of mechanical stimulation in the tissue engineering process leads to an improvement in the structural and biomechanical properties of these tissues and offers new possibilities in the management of joint injuries and degenerative diseases. Remarkably, the stiffness was enhanced in our setting after initial compression of the construct in the glass cylinder without observing a negative influence on cell viability. Further studies need to clarify the influence of compression and various mechanical and hydrostatic stress patterns over different periods of time.