Despite the periodical and completely interconnected pore network that characterizes rapid prototyped scaffolds, cell seeding efficiency remains still a critical factor for optimal tissue regeneration. This can be mainly attributed to the current resolution limits in pore size. We present here novel three-dimensional (3D) scaffolds fabricated by combining 3D fiber deposition (3DF) and electrospinning (ESP). Scaffolds consisted of integrated 3DF periodical macrofiber and random ESP microfiber networks (3DFESP). The 3DF scaffold provides structural integrity and mechanical properties, while the ESP network works as a "sieving" and cell entrapment system and offers-at the same time-cues at the extracellular matrix (ECM) scale. Primary bovine articular chondrocytes were isolated, seeded, and cultured for four weeks on 3DF and 3DFESP scaffolds to evaluate the influence of the integrated ESP network on cell entrapment and on cartilage tissue formation. 3DFESP scaffolds enhanced cell entrapment as compared to 3DF scaffolds. This was accompanied by a higher amount of ECM (expressed in terms of sulphated glycosaminoglycans or GAG) and a significantly higher GAG/DNA ratio after 28 days. SEM analysis revealed rounded cell morphology on 3DFESP scaffolds. Spread morphology was observed on 3DF scaffolds, suggesting a direct influence of fiber dimensions on cell differentiation. Furthermore, the ESP surface topology also influenced cell morphology. Thus, the integration of 3DF and ESP techniques provide a new set of "smart" scaffolds for tissue engineering applications.
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