Regenerative Biomaterials

Regenerative biomaterials are an essential component in developing advanced cell and gene therapies for tissue regeneration. The Centre for Craniofacial & Regenerative Biology is at the forefront of regenerative biomaterials discovery and translation, thanks to unique synergies arising from leading expertise in developmental biology, bioengineering and cell technologies.

Members

Mads Bergholt

Lecturer in Biophotonics

Ciro Chiappini

Senior Lecturer in Nanomaterials and Biointerfaces

Eileen Gentleman

Reader in Bioengineering

Andrea Serio

Lecturer in Neural Tissue Engineering

Nanoneedles for topical delivery

Delivery of biologicals to accessible sites such as the skin, eyes and the mucosas can treat a broad range of conditions with minimal invasiveness and high patient compliance. Yet, topical delivery approaches for large, labile molecules remains largely inefficient due a combination of poor delivery and immunogenicity. Our nanoneedle technology can negotiate the local biobarriers to effectively deliver a broad range of nucleic acids, proteins and peptides to the site of interest, with minimal immune modulation. We are testing this approach for the treatment of skin conditions.

Controlling delivery of morphogens

Controlling the spatial and temporal organisation of morphognes across a developing and regenerating tissues is a key to determine their architecture and control their function. Nanomaterials that we are developing in the lab provide a unique ability to regulate the expression of morphogen at the single cell level, unlocking potential for in vitro modelling and in vivo regeneration.

Nanoparticles for tailored ion release

Dissolvable inorganic nanoparticles are an effective source of bioactive stimuli in the form of ions. We developed a new approach to regulate the amounts and kinetics of ion release from few hours to several days, modulating osteogenic signalling in preclinical models.

Disease modelling

Crohn’s disease causes chronic intestinal inflammation, and can often lead to fibrotic strictures. The Gentleman Lab creates in vitro models of Crohn’s disease by combining PEG-based hydrogels with human iPSC intestinal organoids. Co-culture of intestinal organoids with rare immune cells (type I innate lymphoid cells) that accumulate in the intestines of Crohn’s disease patients prompts organoids to remodel their extracellular matrix in a process that resembles tissue fibrosis. Ongoing work aims to better understand how cues from the matrix impact the intestinal epithelium and vice versa in Crohn’s disease. They also use PEG hydrogels to study matrix remodelling in blood vessels, which can cause aneurysm, and to understand how matrix cues drive the differentiation of pancreatic organoids.

Regenerative applications

Degeneration of the cartilage that enables smooth joint movement in the knee, hip and jaw can cause pain and limit mobility. The Gentleman Lab have created injectable hydrogels based on hyaluronic acid, which can deliver cells and other regenerative factors, and that can adhere to the surrounding tissue. They designed a completely aqueous synthesis route, which makes the materials suitable for injection in the head to treat damage to the cartilage of the TMJ. Ongoing work aims to apply the materials in animal models of TMJ damage to foster tissue repair.

Development of label-free 3D molecular imaging of biomaterials

We innovate instrument design and integrate new technologies to offer label-free bioimaging of biomaterials at the molecular level. In label-free bioimaging the detected light originates directly from the interaction between the excitation light and the sample and requires no contrast agents. The interaction can lead to a variety of physical processes, such as light scattering, absorption and fluorescence decay. Specifically, we develop 3D microscopes as well as novel computed tomographic (CT) approaches for tissue imaging.

Assessment of biocomposition in tissue scaffolds

Tissue engineering (TE) has the potential to improve the outcome for patients. The successful clinical translation of this technique as part of a therapy requires the ability to measure extracellular matrix (ECM) production of engineered tissues in vitro, in order to ensure quality control and improve the likelihood of tissue survival upon implantation. We utilize optical spectroscopy to non-destructively monitor construct growth online in a broad range of TE applications in regenerative medicine toward controlled clinical translation.

In vivo monitoring of implanted biomaterials

Traditional histological and immunohistochemical imaging techniques have been essential for characterisation of biomaterials and tissues ex vivo and in vitro. Monitoring the properties of biomaterials in vivo after implantation is essential towards understanding biocompatibility and tissue formation. We develop novel fiber-optic approaches based on techniques such as for example Raman and reflectance spectroscopy in order to characterise biomaterials in vivo.

Shape-Function Relationship in the Nervous System

we have developed a series of platform and tools that allow us to tackle specific questions related to cell shape across the neural lineage and its consequence on neuronal and glial function. Specifically we are interested in the mechanisms that neurons use to adapt to function with an extremely polarised morphology, sometimes having axons up to 1m in length, as well as the mechanisms that link the shape of astrocytes to their functional profile. For these projects we use a combination of on-chip microfluidic devices, advanced molecular imaging, targeted genetic engineering of stem cell populations and micromanipulation of cells within bioengineered devices.

Engineering Principles of Neuronal and Glial Networks

 We use a combination of bioengineered on-chip devices and molecular reporters with human iPSC-derived neurons and astrocytes to direct the assembly of cell networks with known architecture. This allows us to test how the function of a neuronal and glial network is tied to their shape and level of connectivity, and how we can modulate the functional properties of in vitro populations by altering the engineering principles of the networks (e.g. level of interconnectivity between single cells or nodes, identity and subtypes of the cells involved, etc.).

Advanced modelling platform for neurodegeneration and neurotrauma

 We also use the bioengineered platform we have developed to model both neurodegeneration (e.g. Amyotrophic Lateral Sclerosis, Dementias, Parkinson’s Disease) using patient derived stem cell populations, so we can better understand the effect of single causative genetic mutations on the functionality of neural circuits, and test potential new therapies directly on engineered complex networks of neurons and astrocytes.

Bergholt Lab

Optical imaging and spectroscopy offer a unique insight into tissue and cell structures at the biomolecular level. Our research address fundamental challenges for biomaterial and tissue characterisation, and aim to create a step-change in the way that we can decipher biological systems that goes well beyond current state of the art. We innovate new biomedical imaging instrumentation and methods to study interactions between light and cells/tissue in biomaterials. We aim to develop highly successful label-free biophotonic-based tools, discoveries in biomedicine and technologies that will ultimately create impact on human health.

Bergholt Lab website

Chiappini Lab

Nanomaterials have the same size and can easily interact with the basic building blocks of life, such as proteins, nucleic acids and metabolites allowing. We engineer and innovate nanomaterials to control the delivery of drugs to cells and tissue and to manipulate the cell microenvironment for regenerative applications in vitro and in vivo.

Chiappini Lab

Chiappini Lab website

Gentleman Lab

Hydrogels are water-swollen polymer networks that can mimic many characteristics of the native extracellular matrix. The Gentleman Lab designs and synthesises hydrogels suitable for encapsulating cells and multi-cellular structures and uses these constructs for disease modelling and regenerative applications.

Gentleman Lab

Gentleman Lab Website

Serio Lab

We are interested in combining bioengineering, advanced imaging techniques and stem cell modelling to create new modelling platforms dedicated to Neural Circuit Engineering (NCE) and Neurotechnology, and use them to obtain novel insights into how the nervous system functions in health and disease. We focus. By creating novel bio-mimetic neural tissue engineering platforms we aim to shed light on how neuronal circuitry develops and connects different areas of the nervous system and other organs sometimes across vast distances. We aim to tackle both fundamental questions in the field of neurobiology (e.g. how neurons sense their own length and how decisional processes are made in the formation of neural circuits, what is the relationship between shape and function in glial cells), as well as open questions on the mechanisms leading to neurodegenerative disorders (e.g. how are certain types of neurons vulnerable to diseases but not others, what is the role of cellular shape and response to stress in glial cells), pushing the edge of what is currently achievable with stem cell modelling.

Serio Lab