Modeling the Effect of TNF-α upon Drug-Induced Toxicity in Human, Tissue-Engineered Myobundles.

A number of significant muscle diseases, such as cachexia, sarcopenia, systemic chronic inflammation, along with inflammatory myopathies share TNF-α-dominated inflammation in their pathogenesis. In addition, inflammatory episodes may increase susceptibility to drug toxicity. To assess the effect of TNF-α-induced inflammation on drug responses, we engineered 3D, human skeletal myobundles, chronically exposed them to TNF-α during maturation, and measured the combined response of TNF-α and the chemotherapeutic doxorubicin on muscle function. First, the myobundle inflammatory environment was characterized by assessing the effects of TNF-α on 2D human skeletal muscle cultures and 3D human myobundles. High doses of TNF-α inhibited maturation in human 2D cultures and maturation and function in 3D myobundles. Then, a tetanus force dose-response curve was constructed to characterize doxorubicin's effects on function alone. The combination of TNF-α and 10 nM doxorubicin exhibited a synergistic effect on both twitch and tetanus force production. Overall, the results demonstrated that inflammation of a 3D, human skeletal muscle inflammatory system alters the response to doxorubicin.

Three-dimensionally-printed anthropomorphic physical phantom for mammography and digital breast tomosynthesis with custom materials, lesions, and uniform quality control region.

Anthropomorphic breast phantoms mimic patient anatomy in order to evaluate clinical mammography and digital breast tomosynthesis system performance. Our goal is to create a modular phantom with an anthropomorphic region to allow for improved lesion and calcification detection as well as a uniform region to evaluate standard quality control (QC) metrics. Previous versions of this phantom used commercial photopolymer inkjet three-dimensional printers to recreate breast anatomy using four surfaces that were fabricated with commercial materials spanning only a limited breast density range of 36% to 64%. We use modified printers to create voxelized, dithered breast phantoms with continuous gradations between glandular and adipose tissues. Moreover, the new phantom replicates the low-end density (representing adipose tissue) using third party material, Jf Flexible, and increases the high-end density to the density of glandular tissue and beyond by either doping Jf Flexible with salts and nanoparticles or using a new commercial resin, VeroPureWhite. An insert design is utilized to add masses, calcifications, and iodinated objects into the phantom for increased utility. The uniform chest wall region provides a space for traditional QC objects such as line pair patterns for measuring resolution and scale bars for measuring printer linearity. Incorporating these distinct design modules enables us to create an improved, complete breast phantom to better evaluate clinical mammography systems for lesion and calcification detection and standard QC performance evaluation.