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Cell-based therapies aim at regenerating fully functional tissues damaged by surgery, trauma or disease, where their spontaneous repair is insufficient or leads to nonphysiological healing(1). Tissue engineering, based on the combination of suitable progenitor cells with biocompatible scaffolding materials, is the most advocated strategy as it enables both control over cell behavior and retention upon transplantation(2,3). Mesenchymal stem/stromal cells (MSC) are widely accepted as the best candidates in this type of regenerative medicine approach as they are able to differentiate into the three main mesenchymal lineages reaching complete differentiation both in vitro and in vivo, particularly into cells of the musculoskeletal system(4). Therefore, this phenotypic plasticity encourages their main therapeutic application in the regeneration of damaged bone or cartilage, where the clinical demand is not met by satisfactory surgical solutions(2,5-7). Studies of MSC obtained from different sources show that those isolated from bone marrow (bone marrow stromal cells [BMSC]) possess a greater ability to differentiate into the osteogenic lineage both in vitro and in vivo when compared with MSC derived from other tissues(8-11). The use of MSC for bone regeneration can be optimized in a tissue engineering approach where these cells are combined with natural or synthetic matrices able to mimic the extracellular matrix of connective tissue, hence favoring the differentiation of either host migrating progenitors or transplanted cells(3,12). In the latter case, an optimal seeding of the progenitor cells is the required first step to ensure a homogeneous regeneration of the tissue throughout the scaffold. In particular, high seeding density and uniform cell distribution through the scaffold are critical to promote homogeneous tissue formation and achieve clinical success(13). Bioreactors, including spinner flasks and perfusion bioreactors, are a very effective technology to reach this goal and can overcome the limitations of static loading of highly concentrated cell suspensions(14). However, bioreactor-based seeding procedures require one or more days of in vitro culture to allow cell distribution and attachment to the scaffolds(15). On the other hand, it is highly desirable from a clinical point of view to develop intraoperative approaches, whereby progenitors are harvested, seeded onto the scaffold and re-implanted into the patient directly without an in vitro culture step; this allows the operator to minimize the negative effects of cell manipulation(16) and to reduce...

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