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. In particular, we are using ultrasound fields to remotely pattern cell populations for tissue engineering, and provide an on-demand trigger for enzyme catalysis and hydrogelation. This includes:
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 (link: Advanced Materials 2020). This is linked to my research activity in biomaterials & bioimaging.
Acoustic Cell Patterning for Musculoskeletal Tissue Engineering
We used ultrasound standing waves to remotely pattern cells for tissue engineering. This includes the patterning of skeletal myoblasts to engineer muscle tissue with aligned bundles of myotubes and anisotropic tensile properties (link: Advanced Materials 2018), and the patterning of chondrocytes to engineer deep-zone cartilage tissue with oriented collagen fibers (link: Advanced Healthcare Materials 2022). This is linked to my research activity in tissue engineering.
Quantifying Acoustic Cell Patterning using Voronoi Tessellation
We developed a new analytical framework for the quantitative optimization of experimental parameters that affect ultrasound-based cell patterning, such as frequency, amplitude, and material viscosity. We also used this method to track the migration kinetics of acoustically-patterned cells (link: Lab on a Chip 2019).
If you are interested in these topics, you can find more information in these recent reviews (Trends in Biotechnology 2020, Advanced Functional Materials 2020).
Tissue engineering is the growth of artificial tissue constructs that can be used as clinical grafts or as preclinical models of physiology and disease. A major focus of our work is the design and application of biotechnologies that can recreate structural and functional aspects of engineered tissues. This includes:
Brain Organoid Engineering
This study was led by Dr Kaja Ritzau-Reid during her PhD at Imperial College London. We used melt electrospinning writing to print geometrically-defined scaffolds, which we used to control the lumenogenesis of pluripotent stem cells and their subsequent formation into brain organoids (link: Advanced Materials 2023).
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 (link: Advanced Functional Materials 2020). This is linked to my research activity in 3D bioprinting.
Acoustic Cell Patterning for Musculoskeletal Tissue Engineering
We used ultrasound standing waves to remotely pattern cells for tissue engineering. This includes the patterning of skeletal myoblasts into collagen-based hydrogels, which was used to engineer muscle tissue with aligned bundles of myotubes and anisotropic tensile properties (link: Advanced Materials 2018). This is linked to my research activity in ultrasound manipulation.
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 (link: Science Advances 2020). This is linked to my research activity in 3D bioprinting.
Casting Hydrogels with Bio-instructive Gradients
This study was led by Dr Chunching Li during his PhD at Imperial College London. We developed a new method to programme gradients of slow-releasing osteogenic morphogens into cellularized hydrogels, which generated integrated osteochondral tissue constructs (link: Advanced Materials 2019). This is linked to my research activity in biomaterials & bioimaging.
Magnetic Patterning of Morphogen Gradients
This study was led by Dr Chunching Li during his PhD at Imperial College London. We developed a new method for magnetically patterning osteogenic growth factors in cellularized hydrogels, which could guide the engineering of osteochondral tissue (link: Biomaterials 2018). This is linked to my research activity in magnetic manipulation.
Droplet Interface Bilayers for High-resolution Bioprinting
This study was led by Dr Alex Graham during his PhD at the University of Oxford. We 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 (link: Scientific Reports 2017). This is linked to my research activity in 3D bioprinting.
Hybrid Bioinks for Templated 3D Bioprinting
This study was performed in collaboration with Dr Madeline Burke and Dr Ben Carter at the University of Bristol. We showed that the thermal gelation of pluronic could be used as a temporary guide for the printing of cellularized alginate hydrogels, which we used for cartilage and bone tissue engineering (link: Advanced Healthcare Materials 2016). This is linked to my research activity in 3D bioprinting.
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 (link: Nature Communications 2015). This is linked to my research activity in biomolecular conjugation.
If you are interested in these topics, you can find more information in some of our recent reviews (Science Translational Medicine 2020, Tissue Engineering Part A 2019, Trends in Biotechnology 2020, Advanced Functional Materials 2020, Trends in Biotechnology 2020)
Biomaterials are used to interface with living systems while bioimaging is used to understand living structures and processes. We are interested in developing new regenerative biomaterials and new imaging modalities. Previous work includes:
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 liposomes, releasing calcium ions that could then activate an enzyme (transglutaminase) to catalyze the gelation of fibrinogen (Advanced Materials 2020). This is linked to my research activity in ultrasound manipulation.
Regulation of Stem Cells using Silicon Nanoneedle Arrays
This study was led by Dr Hyejeong Seong during her postdoc at Imperial College London. We 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).
Immunogold FIB-SEM
This study was led by Dr Sahana Gopal during her PhD at Imperial College London. We developed a technique for using immunogold labelling in combination with focussed ion beam scanning electron microscopy (FIB-SEM), which we used to visualize protein expression and cell ultrastructure in 3D (Advanced Materials 2019).
Raman Imaging of Zebrafish
This study was led by Dr Hakon Hogset during his PhD at Imperial College London. We developed a method of using confocal Raman spectroscopic imaging (cRSI) to generate biomolecular maps of living zebrafish embryos (Nature Communications 2020).
Casting Hydrogels with Bio-instructive Gradients
This study was led by Dr Chunching Li during his PhD at Imperial College London. We developed a new method to programme gradients of slow-releasing osteogenic morphogens into cellularized hydrogels, which generated integrated osteochondral tissue constructs (Advanced Materials 2019). This is linked to my research activity in tissue engineering.
If you are interested in these topics, you can find more information in these recent reviews (Science Translational Medicine 2020, Trends in Biotechnology 2020, Advanced Functional Materials 2020, and Advanced Functional Materials 2020).
3D bioprinting is a major technological innovation that enables the additive manufacture of living bioinks into complex tissue structures. We are interested in the development of new 3D bioprinting methods and bioinks. Previous work includes:
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 (link: Advanced Functional Materials 2020). This is linked to my research activity in tissue engineering.
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 (link: Science Advances 2020). This is linked to my research activity in tissue engineering.
Droplet Interface Bilayers for High-resolution Bioprinting
This study was led by Dr Alex Graham during his PhD at the University of Oxford. We 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 (link: Scientific Reports 2017). This is linked to my research activity in tissue engineering.
Hybrid Bioinks for Templated 3D Bioprinting
This study was performed in collaboration with Dr Madeline Burke and Dr Ben Carter at the University of Bristol. We showed that the thermal gelation of pluronic could be used as a temporary guide for the printing of cellularized alginate hydrogels, which we used for cartilage and bone tissue engineering (link: Advanced Healthcare Materials 2016). This is linked to my research activity in tissue engineering.
If you are interested in any of these topics, you can find out more information in this recent review (Advanced Functional Materials 2020).
Biomolecules (e.g., proteins, DNA) can be chemically modified to provide new structures or functionalities. We have previously created artificial membrane-binding proteins that could endow cells with new functional properties:
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 (link: Nature Communications 2015). This is linked to my research activity in tissue engineering.
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 (link: Nanoscale 2016, JoVE 2016). This is linked to my research activity in magnetic manipulation.
Magnetization of DNA and Proteins
This study was led by Dr Paul Brown during his PhD at the University of Bristol. We conjugated magnetic surfactants to DNA and proteins to create magnetically-susceptible biomolecules (link: Advanced Materials 2013). This is linked to my research activity in magnetic manipulation.
You can find out more about these topics in our recent reviews, which discuss the use of modified proteins to functionalize cells (Experimental Biology & Medicine 2016) and extracellular vesicles (ACS Nano 2017).
One aspect of my research is the generation of magnetically-responsive biomolecules. In particular, I seek to create field-responsive systems that can guide tissue engineering processes. This includes:
Magnetic Patterning of Morphogen Gradients
This study was led by Dr Chunching Li during his PhD at Imperial College London. We developed a new method for magnetically patterning osteogenic growth factors in cellularized hydrogels, which could guide the engineering of osteochondral tissue (link: Biomaterials 2018). This is linked to my research activity in tissue engineering.
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 (link: Nanoscale 2016, JoVE 2016). This is linked to my research activity in biomolecular conjugation.
Magnetization of DNA and Proteins
This study was led by Dr Paul Brown during his PhD at the University of Bristol. We conjugated magnetic surfactants to DNA and proteins to create magnetically-susceptible biomolecules (link: Advanced Materials 2013). This is linked to my research activity in biomolecular conjugation.
If you are interested in these topics, you can find more information in these recent reviews, which have further details regarding the use of magnetic manipulation for tissue engineering (Trends in Biotechnology 2020) and biomaterial fabrication (Advanced Functional Materials 2020).