Ultrasound (high-frequency pressure waves) can be used to remotely interact with cells, biomaterials, and tissues. A major focus of our research is the development of new ultrasound-based technologies for driving the assembly of biomaterials and engineered tissues.
- Acoustic Cell Patterning for Musculoskeletal Tissue Engineering: We have pioneered the use of ultrasound standing waves to remotely pattern living cells for musculoskeletal tissue engineering (see our review in Trends in Biotechnology 2020). This includes the patterning of skeletal myoblasts to engineer muscle tissue with aligned bundles of myotubes and anisotropic tensile properties (Advanced Materials 2018) and the patterning of chondrocytes to engineer deep-zone cartilage tissue with oriented collagen fibers (Advanced Healthcare Materials 2022). We have also developed an analytical framework for the quantitative optimization of experimental parameters that affect ultrasound-based cell patterning, such as frequency, amplitude, and material viscosity (Lab on a Chip 2019).
- Ultrasound Manipulation: Mario Ortega Sandoval developed ultrasound tweezers that could be used to manipulate large particles underwater. Working with Martha Lavelle, we demonstrated proof-of-concept manipulation of fixed neuroectoderm aggregates, paving the way toward a new biofabrication technology (Applied Physics Letters 2024).
- Ultrasound-triggered Enzyme Catalysis and Enzymatic Hydrogelation: This study was led by Dr Valeria Nele during her PhD at Imperial College. We used ultrasound to controllably permeabilize calcium-loaded liposomes, releasing the ion cargo to activate an enzyme (transglutaminase) and catalyze the gelation of fibrinogen (Advanced Materials 2020).
Organoids are 3D multicellular structures that can recapitulate many of the structural and functional features of human tissues. We are particularly interested in brain organoids, derived from pluripotent stem cells, and cancer organoids, derived from patient biopsies. We are now developing technologies that can be used to engineer and interrogate organoid cultures.
- Ultrasound Manipulation: Mario Ortega Sandoval developed ultrasound tweezers that could be used to manipulate large particles underwater. Working with Martha Lavelle, we demonstrated proof-of-concept manipulation of fixed neuroectoderm aggregates, paving the way toward a new biofabrication technology (Applied Physics Letters 2024).
- Brain Organoid Engineering: Dr Kaja Ritzau-Reid, during her PhD at Imperial College London, used melt electrowriting to 3D print geometrically-defined scaffolds, which could control the lumenogenesis of pluripotent stem cells and their subsequent formation into brain organoids (Advanced Materials 2023).
Biomaterials are used to interface with living systems. We are particularly interested in the rational design of spatially patterned and responsive biomaterial systems, in particular hydrogels that can be harnessed for cell manipulation, tissue engineering, and endogenous tissue repair (Advanced Functional Materials 2020). We are increasingly interested in the development of biomaterials for clinical applications (Science Translational Medicine 2020).
- Casting Hydrogels with Bio-instructive Gradients: We are interested in the design of gradient biomaterials that can be used to spatially modulate cell behaviour (see our review Trends in Biotechnology 2020). Dr Chunching Li, during his PhD at Imperial College London, developed two new methods to programme gradients of slow-releasing osteogenic morphogens into cellularized hydrogels. These were used to generate integrated osteochondral tissue constructs (Biomaterials 2018, Advanced Materials 2019).
- Cardiovascular Tissue Grafts: We are interested in the development of biomaterials for the surgical treatment of congenital heart disease. Amy Harris, during her PhD at the Bristol Heart Institute, has developed a method for the decellularization of porcine right ventricular outflow tracts using 3D printed flow chambers (STAR Protocols 2024).
- Regulation of Stem Cells using Silicon Nanoneedle Arrays: Dr Hyejeong Seong, during her postdoc at Imperial College London, showed that nondegradable nanoneedle arrays could be used for the long-term culture of stem cells, and that tip sharpness could be used to regulate stem cell alignment, nuclear impingement, and gene expression (ACS Nano 2020).
Bioprinting is a major technological innovation that enables the additive manufacture of living bioinks into complex tissue structures. We are particularly interested in bottom-up bio-assembly for tissue engineering (Advanced Functional Materials 2020) and the development of new technologies and bioinks that expand the possibilities of bioprinting.
- In Situ Endothelialization: This study was led by Dr Liliang Ouyang during his postdoc at Imperial College London. We developed a void-free bioprinting method as a highly efficient, in-situ approach to endothelialization that avoided the need for post-seeding (Advanced Functional Materials 2020).
- 3D Printing “Unprintable” Hydrogel Bioinks: This study was led by Dr Liliang Ouyang during his postdoc at Imperial College London. We developed a new method that used the thermal gelation of gelatin to enable the bioprinting of conventionally “unprintable” hydrogel bioinks for cell culture and tissue engineering (Science Advances 2020).
- Droplet Interface Bilayers for High-resolution Bioprinting: This study was led by Dr Alex Graham during his DPhil at the University of Oxford, who printed cells within water-in-oil emulsions that formed droplet interface bilayers upon assembly, and demonstrated that this method could be used for high-resolution bioprinting (Scientific Reports 2017).
- Templating Bioinks: We used the thermal gelation of pluronic as a temporary guide for the printing of cellularized alginate hydrogels (Advanced Healthcare Materials 2016). We have since collaborated with the Scarpa Group to reinforce this bioink with flax fibres, that provide enhanced load-bearing and enable hygromorphic actuation (Soft Matter 2024).
Biomolecules (e.g., proteins, DNA) can be modified to provide augmented structure or function. We are particularly interested in the development of chemical bioconjugation methods that can endow biological membranes with new functionalities for tissue engineering and regenerative medicine (Experimental Biology & Medicine 2016, ACS Nano 2017).
- Oxygenation of Cartilage Tissue: We developed cell-binding myoglobin conjugates that could oxygenate mesenchymal stem cells and reduce heterogeneous matrix formation during cartilage tissue engineering (Nature Communications 2015).
- Ultra-fast Cell Magnetization: This study was performed in collaboration with Dr Sara Carreira during her PhD at the University of Bristol. We showed that chemical cationization of magnetoferritin could be used to rapidly magnetize cells for magnetic resonance imaging (Nanoscale 2016, JoVE 2016).
- Magnetization of DNA and Proteins: Dr Paul Brown, during his PhD at the University of Bristol, conjugated magnetic surfactants to DNA and proteins to create magnetically-susceptible biomolecules (Advanced Materials 2013).
Bioimaging is our window into the structure and dynamics of cells and tissues. Understanding the interactions between cells and biomaterials is central to our work, and we are particularly interested in bioimaging modalities that can provide insight in a non-destructive, label-free manner.
- Raman Imaging of Zebrafish: Dr Hakon Hogset, during his PhD at Imperial College London, developed a method of using confocal Raman spectroscopic imaging (cRSI) to generate biomolecular maps of living zebrafish embryos (Nature Communications 2020).
- Immunogold FIB-SEM: Dr Sahana Gopal, during her PhD at Imperial College London, developed a technique for using immunogold labelling in combination with focussed ion beam scanning electron microscopy (FIB-SEM) to visualize protein expression and cell ultrastructure in 3D (Advanced Materials 2019).