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Simulators on steam for mac. Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2).
How to install vray for sketchup 2016 mac. Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation.
Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect. Introduction Cell-based advanced therapy medicinal products (ATMPs) have the potential to transform our health care systems, especially for patients with failing intrinsic tissue regeneration such as complex and large bone defects in compromised biological conditions (). The standard approach of this strategy typically includes: (1) donor cells to form tissues together with available host cells, (2) stimulatory factors to direct cellular processes, and (3) biomaterials to provide cells with 3D cues (). Despite major advances in the design, production and in vitro performance of ATMPs, only a fraction displays suitable characteristics for clinical translation (). Major reasons for this lack in clinical monetization of research efforts can be attributed to a poor design and lack of robust manufacturing protocols.
In terms of the design, a biomimetic strategy inspired by developmental embryology provides a scientific foundation and offers key clues regarding the main players, sequences of events and 3D stimulatory cues in postnatal fracture healing (,,, ). Previous reports established that large bone defects mainly heal through the formation of an intermediate cartilaginous callus ().