Advanced Manufacturing Research for Healthcare

Inventing novel methods for making fine bubbles, particles, capsules and fibres of the micro-nano scale is an essential part of modern advanced science and engineering. These structures play an important part in key areas like healthcare engineering which is of a very high utilitarian value and public demand. Microbubbles are crucial contrast agents in ultrasound imaging, and also very effective in drug delivery. Particles and capsules are extensively used in modern therapeutics. Fibres are used in advanced applications such as tissue engineering, microbial screening and chronic wound healing strategies. However, the quest to make these structures in a reproducible manner with high productivity and process control is still elusive and is a hot topic where scale-up possibilities and actual industrial manufacturing are crucial factors. The Biomaterials Processing & Forming Laboratory (www.edirisinghelab.com) has been at the forefront of this research and this talk will illustrate how these novel making developments are currently taking place at great pace. This work has led to many inventions and has won over 20 high impact factor international journal front covers. For example, microbubble generation using microfluidics and electrohydrodynamics and their combination has led to a new medical frontier (1), we are the inventors of the combined method. We have also invented new electrohydodynamic devices which can make 4-layered particles (2) and these are paving the way to a new generation of therapeutics, for example to combat urinary tract infections in a new way. We have invented a new fibre manufacturing method called pressurised gyration (3) which has allowed doped-manufacturing of polymeric fibres with a high yield and this has revolutionized fibre-mesh generation for making antimicrobial filtration mats, tissue engineering constructs and wound healing and drug delivery patches. Our work has also paved new ways of utilising graphene and its derivatives in biomedical engineering (4). More exciting developments are in progress in collaboration with USA, China and Europe to further harness these manufacturing technologies especially in biotechnology (5) and core-sheath structure generation to enhance biomedical applications (6) and this talk will briefly indicate the exciting progress we are making in these areas. 
References 
 
M.Edirisinghe and S.Dalvi, Langmuir, 2019, Volume 35, Issue 31 (special issue), pages 9995-10222 S.Labbaf, H.Ghanbar, E.Stride and M.Edirisinghe, Macromol Rapid Commun. 2014; 35(6), 618–623. P.Heseltine, J.Ahmed and M.Edirisinghe, Macromol Mater. & Eng., 2018, Vol. 303((9), 1800218. M.Edirisinghe, The Royal Society Interface Focus, Special Issue, April 2018, Vol. 8, issue 3. J.Ahmed, M.Gultekinoglu and M.Edirisinghe, Biotech. Adv., 2020, Volume 41, July-August issue, 107549. S.Mahalingam, R.Matharu, S.Homer-Vanniasinkam and M.Edirisinghe, Appl. Phys. Rev., 2020, 7, 041302 .

• When the channel gap size is greater than the diameter of capillary, fission process occurred  Filters were tested using phosphate buffered saline solution spiked with high concentrations of Pseudomonas aeruginosa and Staphylococcus aureus. The bacterial suspensions were passed through a peristaltic pump at 500 mL min -1 to simulate standard UK tap pressure.
The viability of bacterial populations were quantified and analysed using flow cytometry to determine live and dead cells after filtration.

Electrospinning
Pressurised Gyration -Voltage can be adjusted very incrementally to give great control over final fibre morphology -Flow rate is carefully governed to suit desired application and fibre size -Collection distance can be altered to optimise fibre production by controlling fibre drying times -Needle size can also have an effect on fibre production and morphology -Rotation speed influences centrifugal force and can be adjusted to control fibre morphology -Applied gas pressure can also be increased to reduce fibre diameter, and control bead production -Collection distances and setups do influence fibre structure -Relative humidity can be used to regulate drying times and thus fibre morphology -Melt temperature and infusion rate can further used to regulate fibre production

Differences in Fibre Production Rate Electrospinning
Pressurised Gyration -Typical flow rates are 50-150 μL/min in a single needle setup -Typical fibre production in 1 hour is approximately 0.6 grams of fibre for normal single-needle nanofibre setups -Can be scaled up with multiple needle set-ups and advanced needle and collector devices which minimise solutionrelated problems -5mL of polymer solution can be produced into fibres in 15 seconds -Typical fibre production rate in 1 hour is approximately 120 grams -Infusion gyration can further increase production rate to exceed 6 kg/hour -Just like electrospinning, multiple gyration pot setups can be created to increase production rate

Electrospinning
Pressurised Gyration -Without a modified collector electrospun fibres form mesh-like fibres useful in mimicking the ECM -Increased collection times allow for stacking up of layers to create 3D structures -Very low fibre diameters can be achieved as low concentration polymers can be used -PG fibres can easily form highly aligned structures suitable for use in neural tissue engineering -The fibres can be collected into mats, bandages and other shapely materials and used directly as bandages without an additional step -High production capable of fulfilling demand in medical scenarios

Differences in physical applications Electrospinning
Pressurised Gyration -Can be used to create filters with small mesh sizes that are capable of trapping microbes -Portable EHD gun can be used to coat a layer of protective fibres directly onto the wound site in an emergency state -Rapid spinning process allow for macroscaled materials to be produced fast allowing for use in more physical applications such as wound dressings -As the spinning material does not have to be in a solution, a wide range of antimicrobial and pro wound-healing additives can be incorporated into the o Materials including hydrogels, decellularized dermal porcine dermal matrix and freezing dried or gas foaming scaffolds have been studied for wound healing applications, however, lack the ability to recapitulate the architecture of the skin's extracellular matrix o A new generation of wound dressing materials is anticipated to have a higher moisture level, and thereby provide sustained release results, which will enhance the healing of wounds due to the distinctive biological and non-sterile wound environment and to the difficult process of wound healing 1-3 .
o Pressurised gyration is selected in this research because of its ability to mass produce bandage like meshes with simple separation and enhanced process control 4 .

Antimicrobial peptide structures
Fourier-transform infrared spectroscopy