Mesenchymal stem cells (MSCs) are regarded as a potential autologous source for cartilage repair, because they can differentiate into chondrocytes by transforming growth factor‐beta (TGF‐β) treatment under the 3‐dimensional (3‐D) culture condition. However, more efficient and versatile methods for chondrogenic differentiation of MSCs are still in demand for its clinical application. Recently, low‐intensity ultrasound (LIUS) was shown to enhance fracture healing in vitro and induce chondrogenesis of MSCs in vitro. In this study, we investigated the effects of LIUS on the chondrogenesis of rabbit MSCs (rMSCs) in a 3‐D alginate culture and on the maintenance of chondrogenic phenotypes after replating them on a monolayer culture. The LIUS treatment of rMSCs increased: (i) the matrix formation; (ii) the expression of chondrogenic markers such as collagen type II, aggrecan, and Sox‐9; (iii) the expression of tissue inhibitor of metalloprotease‐2 implicated in the integrity of cartilage matrix; and (iv) the capacity to maintain the chondrogenic phenotypes in a monolayer culture. Notably, LIUS effects were clearly shown even without TGF‐β treatment. These results suggest that LIUS treatment could be an efficient and cost‐effective method to induce chondrogenic differentiation of MSCs in vitro for cartilage tissue engineering.

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Multi-plant production planning problem deals with the determination of type and quantity of products to produce at the plants over multiple time periods. Hierarchical production planning provides a formal bridge between long-term plans and short-term schedules. A hybrid simulation-based hierarchical production planning architecture consisting of system dynamics (SD) components for the enterprise level planning and discrete event simulation (DES) components for the shop-level scheduling is presented. The architecture consists of the Optimizer, Performance Monitor and Simulator modules at each decision level. The Optimizers select the optimal set of control parameters based on the estimated behaviour of the system. The enterprise-level simulator (SD model) and shoplevel simulator (DES model) interact with each other to evaluate the plan. Feedback control loops are employed at each level to monitor the performance and update the control parameters. Functional and process models of the proposed architecture are specified using IDEF. The internal mechanisms of the modules are also described. The modules are interfaced using High Level Architecture (HLA). Experimental results from a multi-product multi-facility manufacturing enterprise demonstrate the potential of the proposed approach.