Alternatively, several in vivo studies have demonstrated the need for a vascular supply to promote healing of meniscal lesions, inducing proliferation of vessels, endothelial cells and mesenchymal cells, and resulting lower in fibrovas cular scar tissue repair. However, proliferation of endothelial cells by vascular endothelial growth fac tor coated sutures was not sufficient to pro mote healing of meniscal lesions in the avascular region of sheep menisci. The importance of meniscal cell migration and proliferation in meniscal healing is evidenced by a study showing that donor cells from fresh meniscal allografts in the goat do not survive but the host cells migrate into the allograft and repopulate the transplant.

In addition, in canine menisci containing devitalized meniscal plugs, cells migrate across the bridging tissue and into the interface, ultimately migrating Inhibitors,Modulators,Libraries into the devitalized plugs, remodeling the matrix, and filling the interface with a hyaline fibrocartilage Inhibitors,Modulators,Libraries matrix. Cell migration and or proliferation are necessary for endogenous meniscal healing and repair. In order to repair a meniscal tear, cells must repopulate the wound and synthesize new extracellular matrix to achieve inte grative repair. However, if cells are not able to fill in the gap, as in the presence of inflammatory cytokines, synthesis of reparative tissue and integrative repair can not occur. Additionally, IL 1 treatment up regulates MMP activity that promotes the catabolism of the meniscal extracellular matrix.

Therefore, a variety of strategies, including blocking proinflammatory cytokines, inhibiting MMP activity, and or using anabolic growth factors to increase matrix synthesis and promote cellular proliferation, Inhibitors,Modulators,Libraries may be required to promote meniscal healing following an injury and to increase the success Inhibitors,Modulators,Libraries of tissue engineering constructs. Conclusions In conclusion, we have shown that the inflammatory cytokines IL 1 and TNF a suppress the proliferation of meniscal cells and suppress integrative meniscal repair, while TGF b1 overall does not alter the proliferation of cells or meniscal repair. In inner zone meniscal cells, migration is increased by IL 1 treatment but not enough to overcome the suppression of proliferation and fill the micro wound. However, all other factors did not alter cellular migration independent of proliferation.

There fore, the suppression of cellular proliferation by IL 1 and TNF a may prevent integrative repair of meniscal lesions by decreasing cell accumulation in the wound, and Inhibitors,Modulators,Libraries consequently diminishing the available cell popula tion that can mediate the synthesis of reparative tissue. Therefore, strategies sellectchem that promote the proliferation of meniscal cells may be able to enhance integrative repair following injury and promote the success of tissue engi neered constructs.