The role of computer aided design/computer assisted manufacturing (CAD/CAM) and 3- dimensional printing in head and neck oncologic surgery: A review and future directions.

Microvascular free flap reconstruction has remained the standard of care in reconstruction of large tissue defects following ablative head and neck oncologic surgery, especially for bony structures. Computer aided design/computer assisted manufacturing (CAD/CAM) and 3-dimensionally (3D) printed models and devices offer novel solutions for reconstruction of bony defects. Conventional free hand techniques have been enhanced using 3D printed anatomic models for reference and pre-bending of titanium reconstructive plates, which has dramatically improved intraoperative and microvascular ischemia times. Improvements led to current state of the art uses which include full virtual planning (VP), 3D printed osteotomy guides, and patient specific reconstructive plates, with advanced options incorporating dental rehabilitation and titanium bone replacements into the primary surgical plan through use of these tools. Limitations such as high costs and delays in device manufacturing may be mitigated with in house software and workflows. Future innovations still in development include printing custom prosthetics, 'bioprinting' of tissue engineered scaffolds, integration of therapeutic implants, and other possibilities as this technology continues to rapidly advance. This review summarizes the literature and serves as a summary guide to the historic, current, advanced, and future possibilities of 3D printing within head and neck oncologic surgery and bony reconstruction. This review serves as a summary guide to the historic, current, advanced, and future roles of CAD/CAM and 3D printing within the field of head and neck oncologic surgery and bony reconstruction.

Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2).

Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface. Protein and mRNA expression analyses revealed that kidney proximal tubules express transmembrane fatty acid transporter-2 (FATP2), encoded by Slc27a2, but not the other candidate transporters CD36 and free fatty acid receptor 1. Kidney FATP2 localized exclusively to proximal tubule epithelial cells along the apical but not the basolateral membrane. Treatment of mice with lipidated albumin to induce proteinuria caused a decrease in the proportion of tubular epithelial cells and an increase in the proportion of interstitial space in kidneys from wild-type but not Slc27a2-/- mice. Ex vivo microperfusion and in vitro experiments with NEFA-bound albumin at concentrations that mimic apical proximal tubule exposure during glomerular injury revealed significantly reduced NEFA uptake and palmitate-induced apoptosis in microperfused Slc27a2-/- proximal tubules and Slc27a2-/- or FATP2 shRNA-treated proximal tubule cell lines compared with wild-type or scrambled oligonucleotide-treated cells, respectively. We conclude that FATP2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression.