Functionalised Biopolymers for Regenerative and Therapeutic Soft Robotics

Functionalised Biopolymers for Regenerative and Therapeutic Soft Robotics

Degenerative diseases continuously deteriorate tissue functionality with prolonged cellular senescence and are classified into three main groups: cardiac, neoplastic, and neurodegenerative, all of which feature heavily in global mortality for noncommunicable diseases [1]. An aging population increases prevalence of such diseases stimulating global demand for improved therapeutic techniques [2].

Tissue engineering and regenerative medicine approaches have attempted to improve therapies through active and passive treatments involving scaffolds, stem cell therapies and controlled drug delivery. More recently, active structures exhibiting a change in physiological behaviour upon stimuli exposure have also been fabricated to elicit a biochemical, mechanical, electrical or combined response (also known as soft robots) [6,7].

These have proven feasible through in vivo and vitro studies but are limited by their available materials, often fabricated with synthetic or biological polymers, not present in the native extracellular matrix (ECM). Manipulation of ECM derived materials enhance the biological, chemical, and physical characteristics by mimicking cells external environment.

This exposes several research gaps including (1) availability of electroactive biopolymers (EABPs) derived from the native ECM, (2) post implantation tuneable and dynamic controlled devices, (3) differentiation of induced pluripotent stem cells (iPSCs) into mature cell lines ex vivo (e.g., cardiac and neuronal).

2. Aims and objectives.

Initially this project focuses on the fabrication and characterisation of ECM-based materials to develop 'proof of concept' EABPs. These are hypothesised to operate by applying an electric field such that mobile cations can diffuse through the negatively functionalised film inducing an osmotic pressure gradient, asymmetric swelling and therefore actuation.

A systematic assessment of the electroactivity in these 'proof of concept' novel 2D biopolymeric films will include the characterisation of the electromechanical response, e.g., conductivity, topography, morphology, mechanical properties, and cell viability in relation to altered material composition. Benchmark values should be defined for an optimised electroactive ECM derived biopolymer.

Following optimisation, 3D structures will be fabricated (shown to improved cell adhesion and proliferation) for in vitro experimentation on cardiac, neuronal, and iPSCs. Stimulated cell proliferation, mechanical interactions, angiogenic process and electroactivity can be assessed in relation to growth, differentiation, and maturation, respectively.

The overarching objective is to develop a regenerative, therapeutic, soft robotic biomedical device from ECM derived biopolymers to elicit controlled stimulus driven activity through controlled drug release, electrical stimulation and/or mechanical actuation of model cell lines. 3. Novelty of the research methodology.

Generating ionic EABPs through ECM derived materials, for improved biocompatibility, biochemical stability of the surrounding ECM upon degradation which has been suggested to improve cardiomyocyte maturation in vitro and vivo. The novelty lies within the creation of EABPs solely using ECM derived materials to create a soft robot capable of single or multi stimulatory responses.

Combining well understood fabrication methods with novel ECM derived EABPs to produce resorbable soft robotics with multiple mode functionality. These include the potential for mechanical actuation, electrical stimulation, generation, controlled drug delivery post implantation or a combination of each. However, unlike synthetic materials, functionality is extended within th