SMART Biomaterials

Tissues are dynamic, and so should be the materials that are designed to replace and enhance their function in biomedical devices.

The SMART Biomaterials Team at the IBME aims to replicate the dynamism of tissues across the length scales. Our research is focussed on developing more effective biomaterials with the capability to respond and react to the changing tissue microenvironment in our bodies as we grow and heal from injury. To achieve this, we approach the development of biomaterials that are derived natively from the tissue microenvironment, engineering them to achieve the five SMART strands of behaviour needed for next-generation biodevices: Sensing, Modulating, Adaptive, Regenerative and Therapeutic Functionalities. A few of the key areas of research being undertaken by researchers working with Prof. Malavika Nair in the team to achieve this vision are highlighted below for each strand:

Sensing

Biodegradable metal nanoparticulates (spheres) on electrode surface prior to any treatment. The unconnected spheres mean that while there are metallic particles, there are few connected pathways along the surface that allow for efficient charge transfer.

The electrodes from above following a mild chemical sintering treatment. Sintering (a process of compacting and solidifying the mass) has been achieved here without the application of pressure and heat, allowing these electrodes to be incorporated with heat-sensitive proteins and molecules, while maintaining a conductive surface.

 

Biodegradable Metallic-Collagen Composites for Implantable Electronic Systems

Cells and tissues are fundamentally electric. In order to use electrical signalling between a device and the cellular components of our body, an interface is often required to allow this electrical communication, and is achieve through an electrode. Electrodes enable both electrical stimulation as well as sensing and monitoring of intercellular tissue communication. However, there are many challenges in the application of electronic components to biological systems. There is often a mismatch in the mechanical properties, biological mimicry and electrical mechanisms of charge transfer, and often most solutions available today are permanent. A key area of research in our team is the development of resorbable electrodes that are both conductive and biomimetic. As part of this work, we investigate mechanical and chemical fabrication methods to effectively incorporate collagen with bioresorbable metals to enhance the biochemical and mechanical matching to the tissues of interest, without losing the conductivity required for efficient signal transfer.

Media and Project Credit – Zofia (Zosia) Wolny

 

Project Alumni – Ruth Gregg, Yannan Zhou, Georgina Burgoyne Morris


Modulating

Bio-ionomeric polymers for dynamic tissue engineering 

The success of tissue engineering constructs in restoring healthy tissue function is driven by the interplay of cells with their microenvironmental cues. Therefore, the design of tissue engineering materials is typically guided by ensuring adequate mimicry and regulation of the dynamic biochemical, mechanical, and electrical interactions that occur in the cellular and extracellular milieu. Current approaches to static and stimuli-responsive tissue engineering are limited in their ability to fully capture this dynamic tissue environment. Our solution is to develop electroactive materials that recapitulate key elements of tissue bioelectromechanics, while possessing the ability to be tuned externally by an applied electrical stimulus. By engineering new biologically compatible materials we aim to fabricate clinically translatable and efficacious tissue engineering constructs with the dynamic functionality of soft robots.

 

Media and Project Credit – Matthew Burgess

Project Alumni – Callum Beeston, Ellen Marsh, Aishani Gupta, Antonin Berger

 

 

 

A lab-made mini ventricle model made from a collagen scaffold. A key aspect of ensuring that a tissue engineering construct is capable of replicating the dynamic behaviour of the native healthy tissue, involves replicating the mechanical properties, biochemical cues and physical architecture. In our mini ventricle, we have adapted the processing to replicate the spiral-like structure of the extracellular matrix found in heart tissue.

 

Bionic Platforms for Regenerative Heart Therapies

Cardiovascular diseases (CVDs) are the leading cause of death and disability, costing the UK £28 billion annually. Current cardiac therapies fail to simultaneously support tissue repair, mechanical function, and electrical conduction. The BIONIC HEARTS project aims to develop bio-ionomeric polymers that enhance heart regeneration, improve blood flow, and restore electrical activity. Our solution is to obtain fundamental data on the fabrication and synthesis of bio-ionomeric polymers, to obtain high strains at voltages that are conducive to cell viability, to improve nutrient flow through electrically driven pumping and drift of charged species, and finally to stimulate cardiomyocyte growth and maturation. By combining potential for regeneration and cardiac rhythm control, the bio-ionomeric devices proposed have the potential to reduce the extent of damage and disability caused by heart failure and ischaemic strokes, reduce the need for heart transplants, and improve the quality of life of patients.

Media and Project Credit – Zekun (Jason) Liu

 

 


Adaptive

Control Loops for Dynamic Tissue Engineering Implants 

Soft robots are flexible, have a high specific strength and high response rates which make them ideal for applications requiring sensitive motions whilst remaining compliant. Biopolymers are an attractive material choice for biomedical soft robots: they are abundant, biodegradable, and can offer excellent biomimicry if they are derived from tissue. However, these polymers typically display limited stimulus-driven shape change on their own, with non-linear properties and requiring significant functionalisation and modification. To achieve the range of motion required in some applications, like joint replacement or the pumping mechanism of the heart, it is necessary to investigate the stimulus-driven shape change of different compositions of biopolymers, quantify these results, and identify engineering solutions to stabilise their electromechanical behaviour. One element of this work involves developing an understanding of the mechanisms driving the electromechanical behaviour, and developing suitable macroscopic models to account for the inherent variability in using natural polymers, and the development of appropriate control strategies that are cost efficient and suitable for use within a biomedical context.

Media and Project Credit: Delia Persa

 

After obtaining the full electromechanical model describing the behaviour of our materials, it is possible to control the movement of a construct, for instance, a collagen film, using a controller. This schematic illustrates the set-up for including the inputs and outputs to and from an Arduino, a microcontroller, to process visual data on the behaviour of a deflecting film as above, and to vary the input electrical stimuli to maintain a reference deflection as desired.

Modelling is a powerful tool for designing and optimising these bio-integrated systems, providing both a means to simulate parameter variations and a framework for knowledge generation. Here finite element models of of oxygen A. velocity and B. concentration in cell culture media across a porous scaffold have been generated to understand the impact of a changing scaffold structure on cellular populations.

 

Cells & Smart Materials: Modelling Biological Impacts on IPMCs

Synthetic ionic polymer-metal composites (IPMCs) have existed for over 20 years, and more recently biocompatible and naturally derived materials have facilitated IPMCs to function as scaffolds for growing living cells. Although there has been a diverse array of computational models that simulate ion transport, fluid flow, and the resulting stress/strain distribution across the material using continuum mechanics, the impact of cells seeded on these IPMCs, and the IPMCs back on to the growing cells, has been less well understood and characterised. One solution involves employing hybrid modelling approaches to better understand the impact of living cells on the actuation mechanism of IPMCs, where a discrete agent-based cell model is coupled with the continuum mechanics of IPMCs. This allows for a detailed representation of individual cell behaviour, such as adhesion, proliferation, and interaction with the surface while maintaining a macroscopic view of the mechanical and electrochemical response of the IPMC material. By integrating these two modelling frameworks, we can explore how cellular activity alters IPMC performance, offering new insights into developing electroactive scaffolds for tissue engineering.

Media and Project Credit: Ryan Murray


Regenerative

Ultrasound-Mediated Seeding and Vascularisation in Engineered Skin Constructs

The development of large, full-thickness engineered tissues remains a significant challenge in regenerative medicine. For cellular scaffolds above a critical size, insufficient nutrient diffusion and limited cell penetration can lead to the formation of a necrotic core. One strategy involves the investigating the potential of ultrasound-mediated cell seeding and vascularisation (the formation of blood vessels) to mitigate the formation of these necrotic cores in engineered skin tissue constructs. As part of this work, we investigate the ability to fabricate ultrasound-responsive tissue engineering models, and investigate the impact of ultrasound as a stimulus on different aspects that impact tissue growth. As part of engineering such models, we aim to develop an understanding of the impact of ultrasound-mediated cavitation and heating for enhanced nutrient transport as well as on cellular and tissue function.

Media and Project Credit: Veronica Lucian, co-supervised by Prof. Constantin Coussios

 

A collagen scaffold (green) seeded with a co-culture of human dermal fibroblasts and human umbilical vein endothelial cells. The nuclei of all cells are stained blue, and CD31, a surface receptor on the endothelial cells is stained red in this image, highlighting the blood vessels that have been formed in this tissue construct.

Cryoprinting uses a low-temperature surface, allowing us to bypass limitations encountered in typical approaches to 3D printing. This allows us to directly print the material of interest without modifications to the material’s chemistry to generate large scalable structures.

 

3D Cryoprinting for Large-Scale Interface-Free Scaffolds

3D cryoprinting is a technique that utilises a low-temperature surface to improve the manufacturability of soft materials that are difficult to process in other ways due to low shape fidelity. Typical approaches to 3D printing of soft and lowviscosity materials require modifications to the materials chemistry following printing to facilitate solidification, including the incorporation of photopolymerization additives and cross-linking agents or baths, or heat-assisted solvent evaporation. For several biological materials, these approaches have been shown to limit the range of biochemistries or mechanics achievable in the final printed structure, limiting the ability to successfully integrate with biological tissues. Cryoprinting techniques can maintain the bioactivity of natural biopolymers by preserving the original polymer chemistry while controlling the printed geometry by near-immediate freezing of the viscous slurry following deposition, eliminating the need to adapt or heat the material during manufacture. Using these cryoprinting techniques, large, 3D, interfacefree and interconnected mesoporous scaffolds can be successfully produced from dilute aqueous suspensions of structural biopolymers, offering significant potential for improved scaffold biointegration 

Media and Project Credit: Sam Baker-Jones, co-supervised by Prof. Patrick Grant

 


Therapeutic

Embedded Extracellular Vesicle Collagen Scaffolds for Skin Wound Healing

Extracellular vesicles (EVs) are small lipid particles released by cells containing bioactive molecules that mediate intercellular communication. EVs carry a wide range of payloads including that can influence the recipient cells, and can thus trigger a cascade of biological responses required for effective or accelerated tissue repair. The ability of EVs to deliver cargo to specific cells makes them promising candidates for interventional therapies; however, their extraction, storage and deployment in a patient is often rendered challenging by their limited stability outside the body. One solution involves engineering a process by which their stability can be maintained out of the body, and to incorporate them in regenerative implants to accelerate the wound healing process. In order to achieve this, we must first develop an understanding of EVs derived from various cell lines and characterise not only the impact of the storage medium on the EVs, but also of the EVs in the tissue engineered constructs they will be embedded in prior to patient delivery.

Media and Project Credit: Kae Nicolson, co-supervised by Prof. Cathy Ye

 

Scanning electron micrographs of ureteric stents subjected to different simulated encrustration environments 1-2. Pre-encrustation study at magnifications x60 and x200 3-4. Post-encrustation study at magnifications x60 and x200 with zoomed section at magnification of x500

Biodegradable Ureteric Stents 

The placement of ureteric stents is one of the most common interventions used by urologists, in order to facilitate drainage of urine from the kidney to the bladder in the presence of an obstruction. Despite their clinical utility, ureteric stents are often associated with side-effects, leading to patient discomfort and causing a financial burden on healthcare systems. Biodegradable ureteric stents offer a potential solution to stent-associated side effects, while offering potential for drug elution into the system. As part of this project we look into optimising the design, composition and flow profiles to ensure that biodegradable stents engineered for this purpose are suitable for use in a heavily bacteria and mineral-rich environment.

Media and Project Credit: Lauren Gargan, co-supervised by Prof. Dario Carugo, and Prof. Pierre-Alexis Mouthuy

Project Alumni:  Ragini Shet

Key researchers in SMART Biomaterials
Ms Samantha Baker-Jones - DPhil Student
Mr Matthew Burgess - DPhil Student
Ms Veronica Lucian - DPhil Student
Mr Ryan Murray - DPhil Student
Professor Malavika Nair - Academic
Kae Nicolson - DPhil Student