Enabling technologies

In vitro enzymatic degradation of PCL/HA scaffolds for bone tissue engineering. Image courtesy of M. Domingos.

Enabling technologies

Research into novel biomaterials and tissue scaffolds provides the basis to innovate cell culture techniques and the ability to approximate more natural tissue environments, which can enhance the growth of specific cell types, thus enabling regeneration. These technologies, therefore, span multiple tissues and disease areas.

Physical Sciences

Professor Lin Li

Associate Dean of Business Engagement and Development for Faculty of Science and Engineering
Faculty of Science and Engineering
Director of Laser Processing Research Centre
Laser Processing Research Centre
lin.li@manchester.ac.uk<a href="http://www.mace.manchester.ac.uk/our-research/centres-institutes/laser-processing/
Professor Li’s University Profile

Laser Processing and Surface Engineering

The Regenerative Medicine aspects of Professor Li’s research centre around laser pattering implants to improve the bio-compatibility at their surface interface.  This includes laser texturing the surface to bone implants and coronary stents. His other research interests are listed below:

  • Drilling (thermal barrier coated Ni alloys, carbon composites etc)
  • Cutting (composite materials, ceramics, striation-free cutting of metals, pipes and vessels)
  • Welding (dissimilar materials, light alloys, composites and ceramics, graphene, thick sections)
  • Surface engineering (hardening, coating, cladding, sealing cracks/porosity, texturing, cleaning)
  • Additive manufacturing (rapid tooling, rapid manufacturing, repair, re-manufacturing)
  • Micro-machining for medical applications
  • Nano-manufacturing (nano-surface structures, nano-particles)
  • Hybrid manufacturing (laser-EDM machining, laser/mechanical machining, laser/arc welding)
  • Modelling of laser interactions with materials and effects
  • Nano-imaging

Professor Jian Rai Liu

Head of Biological Physics
Faculty of Science and Engineering
j.lu@manchester.ac.uk
Professor Liu’s University Profile

Physical Properties of Biological Membranes and Surface Interactions

Professor Liu’s research focuses on the manipulation and design membranes towards a specific end, including the designing antimicrobial peptides and bespoke micelles, which can be tuned to optimise cargo loading and unloading.  Professor Liu’s understanding of surface physics has also been used to improve the bio-compatibility of surfaces.

Materials Sciences

Prof Alberto Saiani

Reader in Molecular Materials
Faculty of Science and Engineering
School of Materials
a.saiani@manchester.ac.uk
Prof Saiani’s University Profile

Peptide Hydrogels

Prof Saiani’s research focuses on the characterisation of polymer and biopolymer materials across the length scales and in particular on the understanding of the chemical architecture – thermodynamic – structure – physical property correlations in complex polymeric systems using state of the art techniques which include neutron and X-ray small angle scattering on large scale facilities. His work encompasses a variety of polymeric materials including protein and peptide hydrogels as well as polyurethanes and polyureas elastomers and nanoparticules. He has recently extended his activities into the creation of 3 dimensional hydrogel scaffolds from the self-assembly of de novo designed short peptides. These scaffolds have been further functionalised by conjugating the peptides to pH and temperature responsive polymers.

His research is currently funded by the EPSRC, EU-FP7, Huntsman Polyurethanes and Solvay.

In 2013 he was awarded an EPSRC Research Fellowship

His current research projects are:

  • Responsive hydrogels from polymer-peptide conjugates.
  • 3-D hydrogel formation from self-assembling peptides.
  • Protein based hydrogel for tissue engineering.
  • In Vitro degradation of poly(lactide-co-glycolide) block copolymers.
  • Studies of model segmented polyurethanes elastomers.
  • Associative and bio-adhesive properties of responsive polymers.

Professor Aline Miller

Professor in Biomolecular Engineering
Faculty of Science and Engineering
School of Materials
aline.miller@manchester.ac.uk
Professor Miller’s University Profile

Self Assembly of Peptide Hydrogels

Professor Miller’s research is split in to three distinct subject areas:
1) Understanding and Exploiting Protein Self-Assembly: Professor Miller’s group is exploring the specific rules and general paradigms that govern protein self-assembly. In particular they are concentrating on how proteins un-fold, and self-assemble into fibrillar structures, and subsequently into an array of higher ordered supramolecular structures on the micro, meso and macroscopic length-scales. They are mapping out the phase behaviour of such systems to understand the influence of concentration, pH, ionic strength, temperature and presence of the denaturing agents such as sodium dodecyl sulfate (SDS). This has particular relevance for biopharmaceutical applications and they are also using the knowledge to design novel biomaterials for therapeutic and tissue engineering applications. The organisation and dynamics of such systems at the air-water interface are also of interest.
2) From Fibres to Networks Using Self-Assembling Peptides: Molecular self-assembly is a powerful tool for the preparation of materials with a wide variety of properties. This is illustrated by the abundance of self-assembled proteins and polysaccharides encountered in nature. In particular peptide materials are attracting increasing attention as small peptides are easy to design and synthesise with defined structure and function that self-assemble into 3D structures that are able to support the growth of a wide of variety of cell types. However their effective design and application is currently limited as the fundamental link between building block structure, mesoscopic structure, material properties and cell response has yet to be elucidated. Professor Miller’s group is working towards addressing this by focussing on a number of key-issues to enable understanding and control of peptide self-assembly. Consequently they will be able to direct the morphology (e.g.: fibre size, porosity, roughness) and mechanical properties (e.g.: modulus, viscosity) of our materials and tailor them to specific application needs. In particular they are elucidating the molecular drivers for peptide self-assembly across the length scales by synthesising octa peptides with different amino acid sequences to systematically examine the effect of hydrophobicity, charge distribution and amino acid size/type. They are also fully characterising the structure and properties of the functional self-assembled networks and exploring their potential for therapeutic and clinical application.
3) Surfaces and Interfaces: Professor Miller’s group are interested in understanding and manipulating molecular behaviour at the air-liquid and liquid-liquid interfaces. One avenue they are exploring focuses’ on the ability of surfactants and polymers to promote, or inhibit, crystallization of small molecules. For example, they are using surfactant and hydroxyl based polymers to promote ice crystallisation at the oil-water and air-water interfaces which has implications for the ice-cream industry. This work will be extended to investigate the effect of antifreeze proteins on ice crystal morphology.

Dr Marco Domingos

Lecturer
Faculty of Science and Engineering
marco.domingos@manchester.ac.uk
Dr Domingos’s University Profile

3D Graded Tissue Scaffolds

Dr Domingos’ research focuses on the development of scaffold-based tissue engineering approaches to generate functionalised matrices capable of mimicking the native biomechanical environment and promote the guided regeneration/repair of damaged tissues or organs.  This is an interdisciplinary field where they combine biomanufacturing techniques, biomaterials, cells and biological molecules to produce functional graded structures with enhanced regenerative capacity. Therefore, his particular areas of interest are:

  • Development and application of hybrid biomanufacturing systems for regenerative medicine.
  • Novel biomaterials for skeletal tissue applications.
  • Advanced tissue engineered grafts with optimized structural and functional zonal properties for the treatment of osteochondral defects.
  • Functional graded and multi drug delivery scaffolds for load bearing applications.
  • In vitro models for drug delivery/testing.
  • Hydrogels for cell printing.
  • In situ Biomanufacturing.

Dr Aravind Vijayaraghavan

Lecturer in Nanomaterials
Faculty of Science and Engineering
aravind@manchester.ac.uk
Dr. Vijayaraghavan’s Group Web page

Graphene-Based Materials for Biomedical Applications

Dr Vijayaraghavan’s research group develops graphene based materials for a variety of applications, including biomedical applications such as biosensors, regenerative medicine and drug delivery.

  • Regenerative Medicine: Dr Vijayaraghavan’s group develops 2-dimensional and 3-dimensional graphene scaffolds for cell growth, stem-cell differentiation and tissue repair; current projects involve scaffolds for smooth muscle cells, peripheral nerve cells, haematopoietic stem cells, etc. 2-d scaffolds take the form of graphene coatings on cell-culture plastic and glass substrates as well as other implantable substrate materials. 3-d scaffolds take the shape of graphene hydrogels or graphene/peptide and graphene/polymer composite hydrogels.
  • Therapeutics: The group also produces bio-compatible graphene materials for drug-delivery and other therapeutic applications. In particular, the group focuses on cancer therapies, employing graphene for cancer stem cell differentiation therapy, delivery of water-insoluble cancer drugs and graphene as a promoter in radiation and photothermal therapies.
  • Biosensors: The group develops a range of graphene-based sensors, employing electronic, photonic and plasmonic transduction channels, for chemical, bio-chemical and mechanical stimuli. In particular, the group develops novels ways to biochemically modify the surface of graphene to engineer sensitivity and selectivity to specific target analytes.
  • Underpinning Graphene Technologies: The group has expertise in a number of graphene technologies, including in-house production of highly specified and bio-compatible graphene based materials in dispersion, powder and coating forms, a broad range of physical and chemical characterisation techniques for graphene and employing the clean rooms of the National Graphene Institute to produce electronic and opto-electronic devices of graphene.

Professor Brian Saunders

Professor of Polymer and Colloid Chemistry
Faculty of Science and Engineering
brian.saunders@manchester.ac.uk
Professor Saunders’s University Profile

Injectable Microparticle Gels

One of the major themes within the polymer and colloid chemistry research conducted in the Saunders group is biomaterials. The group is running projects using microgels to repair damaged intervertebral discs (IVDs) and involving responsive polymers. Microgel particles are swellable polymer colloids and the Saunders group have shown that injection of a pH-responsive microgel into degenerated IVDs result in an increase in disc height under biomechanically meaningful loads. This research has resulted in ESPRC Established Career Funding (for BRS) and a Spin Out (Gelexir Healthcare).

Material/Biological Interface

Professor Nicola Tirelli

Professor of Polymers and Biomaterials
Faculty of Biology, Medicine and Health
nicola.tirelli@manchester.ac.uk
Prof Tirelli’s University Profile

Hydrogels and Biologically Reactive Materials

The focus of Professor Tirelli’s group is the molecular design and processing of polymeric materials, in view of their biomedical application. More specifically, they are interested in:

  • Creating new macromolecular structures and providing them with environmental/biological responsiveness, so that they can influence a biological system and be influenced by it. For example, they can be transformed by an inflamed environment and as a result release anti-inflammatory drugs.
  • Producing nanoparticles and other nano-sized colloidal structures for the purpose of (responsive) drug delivery. They  are predominantly interested in drug delivery for cancer treatment and to immune cells and test their materials on advanced in vitro cellular models. Their activities are also part of the NorthWest Centre of Advanced Drug Delivery (NoWCADD) <http://sites.pharmacy.manchester.ac.uk/nowcadd/>
  • Designing new artificial extracellular matrices. In particular, they focus on injectable, remodellable hydrogels, with the aim to provide control over the inflammatory activation of the cells that colonize them.

Professor Kostas Kotsarelos

Professor of Nanomedicine
Faculty of Biology, Medicine and Health
kostas.kostarelos@manchester.ac.uk
www.nanomedicinelab.com
Prof Kostarelos’s University Profile

Nanomedicine

Professor Kostarelos is the head of the Nanomadicien Lab in Manchester; their research has a long history in developing liposomes, colloidal nanoparticulates (polymeric microspheres, solid nanoparticles), natural (e.g. peptide) and synthetic macromolecules (e.g. dendrimers) and novel nanomaterials (e.g. nanocarbons) as vector systems for therapeutic and diagnostic applications. A variety of biologically active entities (peptides, proteins, plasmid DNA, siRNA, stem cells) and more conventional small molecules to achieve anti-angiogenic or cytotoxic activities have been developed along with imaging probes (radionuclides, NIR, opoacoustic) to design multi-functional (theranostic) modalities. The primary therapeutic targets for clinical translation of these technologies are cancer (solid and metastatic) and neurodegenerative disorders.

Professor Sarah Cartmell

Professor of Bioengineering
Faculty of Science and Engineering
sarah.cartmell@manchester.ac.uk
Professor Cartmell’s University Profile

Growth of Bone and Cartilage in Bi-phasic Bio-reactors

Professor Cartmell’s work  involves growing bone, cartilage, tendon and ligament tissue in the laboratory with a view for potentially implanting these tissues into a patient. This means that a patient could receive a newly grown hip joint that will last the rest of the patient’s life rather than needing a metal hip joint prosthesis, which fails after a few years and will need to be replaced. Specifically, her research is involved with the design of a chamber that has the ability to house and grow these orthopaedic tissues in the laboratory. Not only can these tissues be potentially implanted into humans to replaced damaged/diseased tissues, they can also be used by pharmaceutical companies to test new drugs in vitro and hence reduce the number of animals needed for new drug development. Her work has led to the development a variety of different bioreactors for these purposes; two of which include the capability of growing a bone/cartilage plug and and the ability to apply physiologically relevant electrical stimuli to cells and tissues. Additionally, her research is involved with the use of computed tomography (X-rays in 3D) to quantify and characterise novel biomaterials and cellular responses to the novel biomaterials.

Professor Julie Gough

Professor of Biomaterials and Tissue Engineering
Faculty of Science and Engineering
j.gough@manchester.ac.uk
Professor Gough’s University Profile

Tissue Engineering of Mechanically Sensitive Connective Tissues such as Bone, Cartilage, Skeletal Muscle and the Intervertebral Disc

Professor Gough’s research encompases controlling cell responses at the cell-biomaterial interface by engineering defined surfaces. This includes analysis and control of cells such as osteoblasts, chondrocytes, fibroblasts, keratinocytes, myoblasts and macrophages on a variety of materials and scaffolds. Her research also involves development of scaffolds for tissue repair such as novel hydrogels and various porous and fibrous materials.

Professor Brian Derby

Professor of Material Science
Faculty of Science and Engineering
brian.derby@manchester.ac.uk
Professor Derby’s University Profile

Deposition and Patterning of Living Cells and Biological Molecules by Inkjet Printing and the Characterisation of Mechanical Properties of Tissues Using Acoustic Microscopy.

Professor Derby’s research focuses on the deposition and patterning of biological molecules and living cells by inkjet printing.  One of his primary interest lies in the printing of cell sheets;  this involves the printing kidney endothelial cells to create in vitro models of kidney function and the printing of mucosal epithelium for the purposes of repair. He is also involved in the super resolution (1µM) inkjet printing of cell matrix and signalling molecule to determine signalling hierarchy.

Professor derby has a secondary long standing interest in the use of Acoustic Microscopy to determine the stiffness of tissues and cells.

Dr Lu Shin Wong

Lecturer
Faculty of Science and Engineering
l.s.wong@manchester.ac.uk
Dr Wong’s University Profile

Engineering of biologically active micro and nano-patterned surfaces

Dr Wong utilises nanolithpgraphic methods to create micro and nano patterned surfaces with biological activity. His group has utilised this technology to pattern Extra Cellular Matrix (ECM) molecules, such as Fibronectin, with the submicron precision that can address cell surface receptor complexes. These patterned surfaces were then used as substrates for cell culture, demonstrating that patterned Fibronectin surfaces can be direct hMSC towards to oestrogenic fates in the absence of conventional oestrogenic factors, when compared to non-patterned surfaces. Dr Wong has further utilised novel nanolithographic technology to create nano-scale protein arrays, with single molecule resolution and specific directional orientations.

Dr Olga Tsigkou

Lecturer in Biomaterials
Faculty of Science and Engineering
olga.tsigkou@manchester.ac.uk
Dr Tsigkou’s University Profile

Vascularisation of Engineered Tissues

Dr Tsigkou’s research employs novel approaches in stem cells, hydrogels and porous scaffolds for the vascularisation of engineered tissues and the development of 3D in vitro models to mimic the cellular microenvironment. Research efforts of the group also focus on the investigation of the intricate cell-substrate and cell-extracellular matrix interactions for the design of novel bioactive materials for bone and nervous system regeneration.

Dr Annalisa Tirella

Lecturer in Pharmaceutics
Faculty of Medicine, Biology and Health
annalisa.tirella@manchester.ac.uk
Dr Tirella’s University Profile

Generation of 4D Culture Models.

Dr Tirella’s research involves manufacturing engineering and materials sciences for the design and fabrication of biological 3D in vitro models.

Based on an interdisciplinary combination, in vitro model can be engineered to recapitulate key properties and functions of the (patho)physiological environment e.g. stiffness, and ideally integrate one or more cell types. With the use of imaging techniques, the fate of developed 3D in vitro system is ideally tracked over time (hence adding the 4th dimension to the system). Dynamic environment(s) are another alternative way to cultivate 3D systems in a more physiologically relevant fashion e.g. use of perfusion system.

The main core of the research is the translational link between micro- and nano-scales, and their therapeutic applications. For example, material properties can be tailored in their micro features (stiffness, porosity), directing cell behaviour towards a specific state (inflammation by matrix stiffening).

Translational research on nano-formulations can be included in such engineered in vitro models to test targeted delivery e.g. inflammatory reactions.