ABSTRACT
Tissue Engineering of cartilage has been hampered by the inability of engineered tissue to express native levels of type II collagen in vitro. Inadequate levels of type II collagen are, in part, due to a failure to recapitulate the physiological environment in culture. In this study, we engineered primary rabbit chondrocytes to express a secreted reporter, Gaussia Luciferase, driven by the type II collagen promoter, and applied a Design of Experiments approach to assess chondrogenic differentiation in micronutrient-supplemented medium. Using a Response Surface Model, 240 combinations of micronutrients absent in standard chondrogenic differentiation medium, were screened and assessed for type II collagen promoter-driven Gaussia luciferase expression. While the target of this study was to establish a combination of all micronutrients, alpha-linolenic acid, copper, cobalt, chromium, manganese, molybdenum, vitamins A, E, D and B7 were all found to have a significant effect on type II collagen promoter activity. Five conditions containing all micronutrients predicted to produce the greatest luciferase expression were selected for further study. Validation of these conditions in 3D aggregates identified an optimal condition for type II collagen promoter activity. Engineered cartilage grown in this condition, showed a 170% increase in type II collagen expression (Day 22 Luminescence) and in Young's tensile modulus compared to engineered cartilage in basal media alone.Collagen cross-linking analysis confirmed formation of type II-type II collagen and type II-type IX collagen cross-linked heteropolymeric fibrils, characteristic of mature native cartilage. Combining a Design of Experiments approach and secreted reporter cells in 3D aggregate culture enabled a high-throughput platform that can be used to identify more optimal physiological culture parameters for chondrogenesis.
ABSTRACT
Background: Papillary thyroid carcinoma is the most common type of thyroid carcinoma, making up 85-90% of all thyroid carcinomas. Medullary thyroid carcinoma is the third most common type of thyroid carcinoma, making up less than 5% of all thyroid carcinomas. However, synchronous papillary-medullary thyroid carcinoma is exceedingly rare and has not been well described historically. There have been fewer than 40 cases reported in the current literature. Case Description: In this case report we present a 65-year-old man with synchronous papillary-medullary thyroid carcinoma. A 65-year-old man presented with a symptomatic multinodular thyroid goiter. Ultrasound (US) confirmed bilateral thyroid nodules, and he was initially managed nonoperatively. Fine needle aspiration (FNA) biopsy of the left dominant nodule revealed atypia of undetermined significance (AUS) (Bethesda class III). Further assessment of the FNA specimen with ThyGeNEXT® (mutation panel) revealed no mutations and the ThyraMIR® (microRNA risk classifier) was negative, which classified the results as very highly likely to be benign. Due to worsening local compressive symptoms, a total thyroidectomy was performed. Final surgical pathology revealed incidental multicentric, multifocal micropapillary carcinoma foci from (0.1 to 0.5 cm), and a 0.3 cm medullary carcinoma in the left thyroid lobe on the background of nodular hyperplasia. Conclusions: Synchronous papillary-medullary thyroid carcinoma is a rare finding that should be considered in patients with symptomatic multinodular thyroid goiters. It is important to report this case to increase awareness and improve our understanding and management of these unusual carcinomas in the future.
ABSTRACT
Osteobiologics are defined as a group of natural and synthetic materials used to augment bone healing. The selection of the most appropriate osteobiologic from the growing list of available options can be a challenging task. In selecting a material, surgeons should weigh a variety of considerations, including the indication for their use (the when), the most suitable substance (the what), and the correct mode of application (the how). This summary reviews these considerations and seeks to provide the surgeon with a basis for informed clinical evidence-based decision-making in their choice of a successful option.
