With multivariate analysis, age ( > 45 years), percent of round cell differentiation ( > or = 25%), and the presence of spontaneous tumor necrosis are significantly associated with a poor prognosis. No correlation was observed between DNA ploidy (i.e., diploid vs. aneuploid) and percent of round cell differentiation or clinical outcome.

Photo-crosslinkable hydrogels, in particular gelatin methacryloyl (GelMa), are gaining increasing importance in biofabrication and tissue engineering. While GelMa is often described as mechanically 'tunable', clear relationships linking the photocrosslinking conditions to reaction rates, and the resulting mechanical properties, have not been described. Meanwhile the conditions employed in the literature are disparate, and difficult to compare. In this work, in situ rheological measurements were used to quantify the relative rate of reaction of GelMa hydrogels with respect to light intensity, exposure time and photo-initiator concentration. In addition the UV degradation of the photo-initiator Irgacure 2959 was measured by UV-vis spectroscopy, and used to estimate the rate of free radical production as a function of light exposure. Using these data an expression was derived which predicts the mechanical properties of GelMa hydrogels produced across a wide range of crosslinking conditions. The model was validated through fabrication of a GelMa gradient which matched predicted properties. Human mesenchymal stem cells encapsulated in crosslinked GelMa exhibited high (>90%) viability post encapsulation, however metabolic activity over one week was influenced by the intensity of light used during crosslinking. The expressions described may be used to aid rational choices of GelMa photocrosslinking conditions, especially in cell encapsulation experiments where minimising the cytotoxic elements in the reaction is a priority.

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Cartilage injuries cause pain and loss of function, and if severe may result in osteoarthritis (OA). 3D bioprinting is now a tangible option for the delivery of bioscaffolds capable of regenerating the deficient cartilage tissue. Our team has developed a handheld device, the Biopen, to allow in situ additive manufacturing during surgery. Given its ability to extrude in a core/shell manner, the Biopen can preserve cell viability during the biofabrication process, and it is currently the only biofabrication tool tested as a surgical instrument in a sheep model using homologous stem cells. As a necessary step toward the development of a clinically relevant protocol, we aimed to demonstrate that our handheld extrusion device can successfully be used for the biofabrication of human cartilage. Therefore, this study is a required step for the development of a surgical treatment in human patients. In this work we specifically used human adipose derived mesenchymal stem cells (hADSCs), harvested from the infra-patellar fat pad of donor patients affected by OA, to also prove that they can be utilized as the source of cells for the future clinical application. With the Biopen, we generated bioscaffolds made of hADSCs laden in gelatin methacrylate, hyaluronic acid methacrylate and cultured in the presence of chondrogenic stimuli for eight weeks in vitro. A comprehensive characterisation including gene and protein expression analyses, immunohistology, confocal microscopy, second harmonic generation, light sheet imaging, atomic force mycroscopy and mechanical unconfined compression demonstrated that our strategy resulted in human hyaline-like cartilage formation. Our in situ biofabrication approach represents an innovation with important implications for customizing cartilage repair in patients with cartilage injuries and OA.

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Osteosarcoma (OS) remains the most common primary malignant bone cancer affecting children and adolescents. Majority of patients are subjected to surgery and chemotherapy with limited alternatives to consider. However, with increasing knowledge of the molecular pathogenesis of OS, advancements in OS therapy research fields have developed potential agents for a more targeted and localised approach to treatment. Thus, this review attempts to examine some common treatment strategies (surgery, radiotherapy and chemotherapy) employed clinically as well as recent developments in newer experimental therapy methods (gene therapy) which might potentially benefit patients.

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