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D'Souza, R. N.

Publications and source records attributed to D'Souza, R. N..

2 recordsLinked to original sources

Feasibility of clinician-facilitated 3D printing of synthetic cranioplasty flaps

Objectives3D scanning and stereolithographic printing technology becoming increasingly common, however its implementation into clinical practice is in its primacy. These technologies may be esoteric to the practicing neurosurgeon. We explored a range of 3D scanning and stereolithographic techniques to create patient-specific synthetic implants.\n\nMethodsWe simulated bilateral craniectomies from a single cadaveric specimen to create 3 methods of creating stereolithographically-viable virtual models. Firstly, we used pre-and-post operative CT derived bony windows to create a virtual skull model, from which the flap was extracted. Secondly, we used an entry-level 3D light-scanner to scan and render models of the individual bone pieces. Thirdly, we used an arm-mounted, 3D laser-scanner to create virtual models using a real-time approach.\n\nResultsFlaps were printed from the CT scanner and laser scanner models only, in a UV-cured polymer. The light scanner did not produce suitable virtual models for printing. The CT scanner derived models required extensive post-fabrication modification to fit the existing defects. The laser-scanner models assumed good fit within the defects without any modification.\n\nConclusionsThe methods presented varying levels of complexity in acquisition and model rendering. Each technique required hardware at varying in price points from $0 to [~]$100,000. The laser-scanner models produced the best quality parts which bore near-perfect fit with the original defects. We discuss potential neurosurgical applications of this technology.

synthetic biology

The Pax9/Wnt pathway regulates secondary palate formation in mice

Clefts of the palate and/or lip arise in about 1/700 human live births and are caused by multiple genetic and environmental factors. Studies of mouse knockout models of cleft palate have improved our understanding of the molecular control of palatogenesis. While it is known that Pax9 regulates palatogenesis through Bmp, Fgf and Shh signaling, there is still much to learn about its precise relationship with other pathways. Here we show that alterations of Wnt expression and decreased Wnt activity in Pax9-/- palatal shelves are a result of Pax9s ability to directly bind and repress the promoters of Dkk1 and Dkk2, proteins that antagonize Wnt signaling. The delivery of small-molecule Dkk inhibitors (Wnt agonists) into the tail-veins of pregnant Pax9+/- mice from E10.5 to E14.5 restored Wnt signaling, promoted cell proliferation, bone formation and restored the fusion of palatal shelves in Pax9-/- embryos. In contrast, other organ defects in Pax9 mutants were not corrected. These data uncover a unique molecular relationship between Pax9 and Wnt genes in palatogenesis and offer a new approach for treating cleft palates in humans.\n\nSummary StatementThese studies demonstrate that the Pax9/Wnt genes regulate murine palatogenesis. This unique molecular relationship is proven by the correction of cleft defects in Pax9-deficient mice through Wnt agonist therapies.

developmental biology