Nanomedicine

Gene and drug delivery are promising for many disease treatments. However, many of the current methods suffer from low efficiency and high toxicity. Developing nano carriers for gene/drug molecules to improve their bioavailability is at the forefront of the current research. Our interest lies in understanding the solution aggregation of novel polymers and peptides, their complexation with model DNAs/siRNAs and drug molecules and exploring their potential for improved drug and gene delivery.  

Designed peptides for gene delivery

Fig. 1. A, siRNA complexaction with designed peptide at different charge ratios. B, Delivery of siGLO-Red siRNA into HCT cancer cells (colorectal carcinoma cells) by cationic peptides. C, FITC-labelled peptides in MDA cells (breast cancer cells). D, Delivery of siGLO-Red siRNA into HCT cancer spheroids. E, Delivery of siGLO-Red siRNA into a zebrafish by cationic peptides.

Magnetite-silk core-shell nanoparticles for drug and gene delivery

We are also interested in the fabrication of magnetite-silk core-shell nanoparticles for targeted delivery of anticancer drugs (e.g. Curcumin) into human breast cancer cells. 

Fig. 2. A & B, AFM & TEM images of Curcumin loaded magnetite-silk core-shell nanoparticles. C, Image of cell nucleus stained by DAPI. D, Image of cell microfilament stained by Texas Red®-X Phalloidin. E, Image of Curcumin fluorescence delivered using magnetic-silk core-shell nanoparticles. F, Merge of images C, D, and E. 

Printed devices 
Inkjet printing is an emerging technique for surface patterning and 3D fabrication. We are interested in reactive inkjet printing (RIJ) of biomaterials (e.g. silk) for the fabrication of surface patterns, tissure culture scaffolds, and enzyme powered swimming devices.

Reactive inkjet printing of silk micro-rockets

Fig. 3. Left, Example of reactive inkjet printing (RIJ) of silk micro-rockets. a) Schematic of the RIJ process for manufacturing catalytic micro-rockets. Stage 1: Alternate printing of a silk/catalase/PEG ink and a methanol ink (to transform printed silk ink from soluble random coils to insoluble beta-sheet structure) to build the catalytically active base of the micro-rocket. Stage 2: Ten layers of PMMA ink are deposited to act as a divider between the two halves of the rocket (to stop the penetration of oxygen bubbles generated into the inactive part of the micro-rocket). Stage 3: The second half of the rocket is deposited as in stage 1, but a silk/PEG ink is now used. Stage 4: Manufacture complete, substrate is immersed into the fluidic swimming media. Stage 5: Ultrasonication is used to detach the micro-rockets from the substrate. SEM images for micro-rockets: b) overview of silk rocket RIJ array, c) top view of a symmetrically active silk rocket, d) symmetrically active rocket, and e) Janus micro-rocket: red arrow indicates PMMA barrier layer between catalytically active and inactive segments; fluorescent microscopy images of FITC labelled catalase in micro-rockets: f) single ink micro-rocket (symmetrical) and g) Janus micro-rocket. Right, Still frames for A) a fully active and B) a Janus micro-rocket in 2% human serum solution containing 3% wt/V aqueous hydrogen peroxide fuel. Red lines indicate trajectories. 

Reactive inkjet printing of silk micro-stirrers

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Fig. 4. A) A schematic representing the procedure of layer-by-layer reactive inkjet printing of regenerated silk fibroin (RSF) stirrers. Ink A: RSF/PEG400 mixture (yellow), ink B: RSF/Catalase/PEG400 mixture (green) and ink C: methanol curing ink (blue). Stage 1: Printing of ink A in order to build the main body of the silk stirrers. Stage 2: Printing of ink B for the ‘engine’ part of the silk stirrers containing catalase. Stage 3: Printing ink C (methanol) to transform printed RSF from soluble random coil structure into insoluble beta-sheet structure. Stage 4: Stages 1 to 3 are repeated consecutively to form 3D structures. The height of the structures is determined by the number of layers printed. B) Schematic representations of dual-engine and single-engine silk stirrers, illustrating the observed centre of rotation during stirring action. C) A pilot study of the stirrer in fuel solution. Red and Green lines show the trajectories at the two ends of the stirrer. D) Demonstration of stirring effect using a silk stirrer in a 9 cm diameter petri dish. 

Bioprinting

It is of growing interest to develop novel bio scaffolds for tissue engineering. We are interested in reactive inkjet printing of regenerated silk fibroin peptides as well defined scaffolds for cell culture.

Reactive inkjet printing of silk micro-patterns for cell culture

Fig. 5. a, inkjet printed dots and channels of silk ink; b, printed "SHEFFIELD ENGINEERING" pattern; c, printed silk scaffold channels; d, L929 cells growing on a printed silk scaffold.

Inkjet printing of self-assembled peptide nanoscaffolds for cell patterning

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Fig. 6. A, Self-assembled I3K peptide nanofibers; B, PC12 neuronal cell growing on I3K peptide nanoscaffolds; C, Inkjet printed peptide nanofiber scaffold lines; D, PC12 cells growing alone the printed pattern; E, DAPI and Phalloidin staining of the PC12 cells.

Biointerfaces & Biosensors

Biosensors play important roles in many biotechnological and biomedical applications such as cancer diagnostics. The performance of the biosensors significantly relies on the amount and molecular orientation of the biomarkers (e.g. antibodies) immobilized on the sensor electrode surfaces. We are interested in controlling the amount and manipulating the biomarker orientation at the surfaces for optimizing the sensor performance.

FBAR sensors for the detection of human prostate-specific antigen

Fig. 7. Example of a Film Bulk Acoustic Resonator (FBAR) as an immunosensor for the detection of human prostate-specific antigen (hPSA) by coating the anti-hPSA antibody onto the top electrode of the sensor. Left, frequency shift after antibody immobilization. Middle, SEM image and schematic cross-sectional view of the FBAR sensor. Right, Resonant frequency responses of the mass change on the FBAR sensor.