BIOFABRICATION
Biofabrication is the controlled spatial deposition of materials and biological material (termed a bioink when printed simultaneously) and subsequent maturation of the printed tissue structure. It is a rapidly developing technique with commercially available printing hardware now making the field very accessible. Dr. Cooke has worked on the development of suspension bioprinting using fluid gels, which have been sheared during gelation to produce a suspension media. This helps to overcome the limitations of viscosity in bioprinting tissue constructs with good shape fidelity. She is also very interested in how cells and materials interact when combined to form bioinks, and how their interactions affect the processing and printability of bioinks.
Cooke and Rosenzweig, APL Bioengineering 2021
This invited review presents fundamental technical information on the properties of hydrogel polymers before introducing qualitative and quantitative methods methods for characterising 'printability'. We highlight a series of rheological tests that we advise should be performed in the characterisation of bioinks.
We then go on to summarise novel approaches to overcome rheological limitations, such as the use of dynamic biomaterials and suspension bioprinting methods. Throughout we discuss limitations in the field such as standardisation of testing methods and protocols as well as the lack of rheological testing performed on cell-seeded biomaterials.
Moxon and Cooke et al., Advanced Materials 2017
In this article we presented for the first time a novel gel-in-gel printing technique using fluid gel microparticles. Unlike microgels or slurries, these particles have dendritic-like processes that interact with each other resulting in very fast recovery of solid-like properties.
Using this technique we produced osteochondral plugs with spatially defined bone-like and chondral-like regions. Primary human cells were printed within the bioink, the plugs were then matured before their biochemistry was assessed.
Cooke et al., Advanced Materials 2018
In this progress report, we detailed a number of techniques being used in the Grover lab to structure hydrogels to give them new properties. A key driver for this research is the onerous regulatory environment. By taking already approved materials and inducing novel properties the route to translation will be accelerated and financially less cumbersome.
TISSUE STRUCTURE AND MECHANICS
The key functions of cartilage and bone are mechanical, be that in transfer of load through cartilage to the subchondral bone or providing attachment sites for ligaments and tendons in bone. Most tissues have been shown to exhibit viscoelastic mechanical properties. Dynamic Mechanical Analysis (DMA) is therefore an important and powerful testing modality when examining native tissues or producing new biomaterials for tissue engineering. Beyond their mechanics, Meg is fascinated by the changing structures of tissues in health and disease.
Acta Biomaterialia 2018
In this study we investigated the effects of osteoarthritis (OA) on both the viscoelastic and biochemical properties of articular cartilage in the human knee joint.
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The ability of cartilage to store energy (storage modulus) was significantly decreased in OA. This was attributed to a reduction in proteoglycan content as shown by quantitative x-ray fluorescence spectroscopy and in increased unbound water as quantified by thermogravimetric analysis.
Osteoarthritis and Cartilage 2019
In this project, bovine osteochondral cores were assessed for their viscoelasticity. Investigating how the histomorphometry of subchondral bone affected their viscoelasticity.
Journal of the Mechanical Behaviour of Biomedical Materials 2018
This study investigated the effects of hydroxyapatite addition into agarose and gellan hydrogels on the dynamic mechanical properties.
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Biomaterials are often tested in static compression or tension. However, as most tissues in the body have shown to be inherently viscoelastic.
MICROGELS AS GRANULAR TISSUE MATRICES
Microgels are 10-500 um hydrogel particles produced by microfluidic dropletting, emulsions or the application of shear during gelation. By changing fabrication parameters microgels can be tailored regarding their size, morphology, aspect ratio, particle stiffness and packing density. Altering these physical properties elucidates different local (cell-sensing) and global (as a bulk matrix) mechanical properties. As a bulk, granular matrices act as yield stress materials with minimal thixotropy as adhesion forces between particles at rest overcome gravitational forces that would induce flow. When a critical stress is applied, they flow as structured fluids imparting injectability. Their bulk mechanics can be improved by introducing secondary crosslinking mechanisms activated post-injection.
Cooke et al., APL Bioengineering 2017
Fluid gels as a matrix to enable the injectable delivery of chondrocytes to the articular surface of the knee joint.