Search bioRxiv⌕ Search

Biology subjects

Tomkinson, A.

Publications and source records attributed to Tomkinson, A..

2 recordsLinked to original sources

A Biosynthetic Thumb Prosthesis

In cases of severe damage to the extremities, the function and structure of compromised biological tissues must be replaced. If biological reconstruction using autologous tissue is not feasible, amputation and replacement with a synthetic prosthesis is often the next best option. Currently, the synthetic materials available for prostheses are limited, especially in their ability to restore skin sensation. Here we show a biosynthetic prosthesis that combines the versatility of titanium with the rich sensory capabilities of biological skin, to both increase movement and restore sensation to an amputated thumb. The prosthesis recreates opposition pinch by linking motion of the prosthetic joint to that of the residual biological joint. The device is enclosed in neurotized skin from the patients own body, providing natural sensation. We validated the biosynthetic thumbs ability to reproduce opposition pinch on the benchtop and in a cadaver, and showed in vivo viability of the skin interface in an animal model. These results provide a framework for functional reconstruction of amputated digits using a combination of synthetic materials and biological tissues. One Sentence SummaryA prosthetic thumb made up of a titanium mechanism and living skin can restore opposition pinch and touch sensation following thumb amputation.

bioengineering↗

Discovery and Synthesis of GS-7682, a Novel Prodrug of a 4'-CN-4-Aza-7,9-Dideazaadenosine C-Nucleoside with Broad-Spectrum Potency Against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys.

Acute respiratory viral infections (ARVI), such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1) a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV EC50 = 3-46 nM, human metapneumovirus (hMPV) EC50 = 210 {+/-} 50 nM, human rhinovirus (RV) EC50 = 54-61 nM, and enterovirus (EV) EC50 = 83-90 nM. Prodrug optimization for cellular potency and lung cell metabolism identified the 5-methyl((S)-hydroxy(phenoxy)phosphoryl)-L-alaninate in combination with 2,3-diisobutyrate promoieties as optimal for high intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together these finding support additional evaluation of 1 and its analogs as a potential therapeutic for pneumo- and picornaviruses.

biochemistry↗