David A Gregory | The University of Sheffield (original) (raw)

Papers by David A Gregory

NIP & Digital Fabrication Conference, 2016

This is a repository copy of Altering the bubble release of reactive inkjet printed silk micro-ro... more This is a repository copy of Altering the bubble release of reactive inkjet printed silk micro-rockets.

Trends in Molecular Medicine, 2022

Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible and bioresorbable polymers... more Polyhydroxyalkanoates (PHAs) are sustainable, versatile, biocompatible and bioresorbable polymers, suitable for biomedical applications. Produced via bacterial fermentation, under nutrient limiting conditions, they are unravelling a new horizon for devices in biomedical applications. A wide range of cell types including bone, cartilage, nerve, cardiac, and pancreas readily attach, grow and are functional on PHAs. The tuneable physical properties and resorption rates of PHAs allows them to be a toolbox for biomedical engineers in developing devices for hard / soft tissue engineering applications and drug delivery. The versatility of PHAs and the vast range of different PHA-based prototypes are discussed. Current in vitro, ex vivo and in vivo development work are described, and their regulatory approval reviewed.

Frontiers in Bioengineering and Biotechnology, 2021

Graphical Illustration of PHA synthesis followed by a simple muscle inspired chemistry polydopami... more Graphical Illustration of PHA synthesis followed by a simple muscle inspired chemistry polydopamine coating.

Materials Advances, 2021

A simple one-step glancing angle deposition technique is employed to increase the rotational velo... more A simple one-step glancing angle deposition technique is employed to increase the rotational velocity of anisotropic ellipsoidal micro-swimmers.

Journal of Visualized Experiments, 2019

In this study, a protocol for using reactive inkjet printing to fabricate enzymatically propelled... more In this study, a protocol for using reactive inkjet printing to fabricate enzymatically propelled silk swimmers with well-defined shapes is reported. The resulting devices are an example of self-propelled objects capable of generating motion without external actuation and have potential applications in medicine and environmental sciences for a variety of purposes ranging from micro-stirring, targeted therapeutic delivery, to water remediation (e.g., cleaning oil spills). This method employs reactive inkjet printing to generate well-defined small-scale solid silk structures by converting water soluble regenerated silk fibroin (silk I) to insoluble silk fibroin (silk II). These structures are also selectively doped in specific regions with the enzyme catalase in order to produce motion via bubble generation and detachment. The number of layers printed determines the three-dimensional (3D) structure of the device, and so here the effect of this parameter on the propulsive trajectories is reported. The results demonstrate the ability to tune the motion by varying the dimensions of the printed structures.

International Journal of Pharmaceutics, 2018

The lack of efficient and cost-effective methods for gene delivery has significantly hindered the... more The lack of efficient and cost-effective methods for gene delivery has significantly hindered the applications of gene therapy. In this paper, a simple one step and cost effective salting-out method has been explored to fabricate silk-PEI nanoparticles (SPPs) and magnetic-silk/PEI core-shell nanoparticles (MSPPs) for targeted delivery of c-myc antisense oligodeoxynucleotides (ODNs) into MDA-MB-231 breast cancer cells. The size and zeta potential of the particles were controlled by adjusting the amount of silk fibroin in particle synthesis. Lower surface charges and reduced cytotoxicity were achieved for MSPPs compared with PEI coated magnetic nanoparticles (MPPs). Both SPPs and MSPPs were capable of delivering the ODNs into MDA-MB-231 cells and significantly inhibited the cell growth. Through magnetofection, high ODN uptake efficiencies (over 70%) were achieved within 20 min using MSPPs as carriers, exhibiting a significantly enhanced uptake effect compared to the same carriers via non-magnetofection. Both SPPs and MSPPs exhibited a significantly higher inhibition effect against MDA-MB-231 breast cancer cells compared to human dermal fibroblast (HDF) cells. Targeted ODN delivery was achieved using MSPPs with the help of a magnet, making them promising candidates for targeted gene therapy applications.

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due t... more Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to t...

Journal of Functional Biomaterials

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedi... more In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical po...

Macromolecular Bioscience, Jul 7, 2023

Silane modification is a simple and cost‐effective tool to modify existing biomaterials for tissu... more Silane modification is a simple and cost‐effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108‐15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11‐aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X‐ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108‐15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11‐modified fibers significantly support NG108‐15 neuronal cell and Schwann cell viability. NG108‐15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost‐effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration.

Progress in Natural Science: Materials International, 2020

Patterning the neuronal cells via inkjet printing of self-assembled peptides on silk scaffolds.

Frontiers in Cardiovascular Medicine, 2020

Cardiovascular diseases (CVD) constitute a major fraction of the current major global diseases an... more Cardiovascular diseases (CVD) constitute a major fraction of the current major global diseases and lead to about 30% of the deaths, i.e., 17.9 million deaths per year. CVD include coronary artery disease (CAD), myocardial infarction (MI), arrhythmias, heart failure, heart valve diseases, congenital heart disease, and cardiomyopathy. Cardiac Tissue Engineering (CTE) aims to address these conditions, the overall goal being the efficient regeneration of diseased cardiac tissue using an ideal combination of biomaterials and cells. Various cells have thus far been utilized in pre-clinical studies for CTE. These include adult stem cell populations (mesenchymal stem cells) and pluripotent stem cells (including autologous human induced pluripotent stem cells or allogenic human embryonic stem cells) with the latter undergoing differentiation to form functional cardiac cells. The ideal biomaterial for cardiac tissue engineering needs to have suitable material properties with the ability to support efficient attachment, growth, and differentiation of the cardiac cells, leading to the formation of functional cardiac tissue. In this review, we have focused on the use of biomaterials of natural origin for CTE. Natural biomaterials are generally known to be highly biocompatible and in addition are sustainable in nature. We have focused on those that have been widely explored in CTE and describe the original work and the current state of art. These include fibrinogen (in the context of Engineered Heart Tissue, EHT), collagen, alginate, silk, and Polyhydroxyalkanoates (PHAs). Amongst these, fibrinogen, collagen, alginate, and silk are isolated from natural sources whereas PHAs are produced via bacterial fermentation. Overall, these biomaterials have proven to be highly promising, displaying robust biocompatibility and, when combined with cells, an ability to enhance post-MI cardiac function in pre-clinical models. As such, CTE has great potential for future clinical solutions and hence can lead to a considerable reduction in mortality rates due to CVD.

Materials Science and Engineering: R: Reports, 2021

Natural biomaterials have benefited the human civilisation for millennia. However, in recent year... more Natural biomaterials have benefited the human civilisation for millennia. However, in recent years, designing of natural materials for a wide range of applications have become a focus of 61 attention, spearheaded by sustainability. With advances in materials science, new ways of 62 manufacturing, processing, and functionalising biomaterials for structural specificity has 63 become feasible. Our review is focused on bacterial cellulose (BC), an exceptionally versatile natural biomaterial. BC is a unique nanofibrillar biomaterial extruded by microscopic singlecell bacterial factories utilising the chemical energy harvested from renewable substrates. BC is extracellular and is intrinsically pure, unlike other biopolymers that require extraction and purification. BC fibres are 100 times thinner than plant-derived cellulose and exist in a highly porous three-dimensional network that is highly biocompatible. Macro fibres fabricated from BC nanofibrils are stronger and stiffer, have high tensile strength values and can be used as substitutes for fossil fuel-derived synthetic fibres. The increased surface area to volume ratio allows stronger interactions with the components of composites that are derived from BC. The reactive hydroxyl groups on BC allows various chemical modifications for the development of functionalised BC with a plethora of 'smart' applications. In this review we consolidate the current knowledge on the production and properties of BC and BC composites, and highlight the very recent advancements in bulk applications, including food, paper, packaging, superabsorbent polymers and the bio-concrete industries. The process simplicity of BC production has the potential for large scale low-cost applications in bioremediation. Furthermore, the emerging high value applications of BC will be in electrochemical energy storage devices as a battery separator, and in transparent display technologies will be explored. Finally, the extensive biomedical applications of BC are discussed including, wound healing, controlled drug delivery, cancer treatment, cell culture and artificial blood vessels. In a further development on this, additive manufacturing considers enhancing the capabilities for 83 4 manufacturing complex scaffolds for biomedical applications. An outlook on the future directions of BC in these and other innovative areas is presented.

Small, 2018

Stirring small volumes of solution can reduce immunoassay readout time, homogenize cell cultures,... more Stirring small volumes of solution can reduce immunoassay readout time, homogenize cell cultures, and increase enzyme reactivity in bioreactors. However, at present many small scale stirring methods require external actuation, which can be cumbersome. To address this, here, reactive inkjet printing is shown to be able to produce autonomously rotating biocompatible silk‐based microstirrers that can enhance fluid mixing. Rotary motion is generated either by release of a surface active agent (small molecular polyethylene glycol) resulting in Marangoni effect, or by catalytically powered bubble propulsion. The Marangoni driven devices do not require any chemicals to be added to the fluid as the “fuel,” while the catalytically powered devices are powered by decomposing substrate molecules in solution. A comparison of Marangoni effect and enzyme powered stirrers is made. Marangoni effect driven stirrers rotate up to 600 rpm, 75–100‐fold faster than enzyme driven microstirrers, however enz...

Small (Weinheim an der Bergstrasse, Germany), Jan 27, 2016

Inkjet-printed enzyme-powered silk-based micro-rockets are able to undergo autonomous motion in a... more Inkjet-printed enzyme-powered silk-based micro-rockets are able to undergo autonomous motion in a vast variety of fluidic environments including complex media such as human serum. By means of digital inkjet printing it is possible to alter the catalyst distribution simply and generate varying trajectory behavior of these micro-rockets. Made of silk scaffolds containing enzymes these micro-rockets are highly biocompatible and non-biofouling.

International Journal of Molecular Sciences, 2021

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate ... more Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces th...