In-Vitro Material Dynamics of Living Engineered Tissue

: Mechanical Intrumentation and Biofabrication Protocols for Precision Regenerative Medicine Applications

Abstract

Volumetric muscle loss (VML) is the traumatic or surgical loss of skeletal muscle with resultant functional impairment (Grogan 2011). Precision regenerative medicine, the culture of patient specific engineered tissues in-vitro prior to implantation, holds promise for treating volumetric muscle loss, with matched biological and mechanical properties between host and graft. Current methods of measuring mechanical properties of engineered tissues are typically non-sterile and irreversibly attached to the tissue, preventing this form of treatment. This thesis presents three contributions which potentially enable patient-specific muscle graft culture via closed-loop protocol adjustment, which would enable for the first time precision regenerative medicine
treatments with matched graft-host mechanical properties. First, a rotary Lorentz force actuator is developed to apply step responses in force to engineered tissues in-vitro and to measure the corresponding dynamic response. This enables in-vitro dynamic mechanical analysis of acellular and cellularised hydrogels of approximately 0.1 kPa Young’s Modulus. Secondly, a tissue engineering system for repeatably culturing mature, large, contractile engineered muscle tissue under various static strains is developed, with embedded modular interfaces to allow reversible, repeatable connection to mechanical instrumentation. This facilitates fundamental studies on the impact of mechanical loading on cardiac muscle tissue for basic research into heart failure. Lastly, after performing dynamic mechanical analysis on live engineered muscle tissue by connecting both aforementioned systems, a validated transfer function is developed
empirically for describing the dynamic response of the tissue. This unveils interactions between Young’s Modulus, poroelasticity and viscoelasticity through novel metrics such as the natural frequency and damping ratio of an engineered muscle tissue when connected to a reference inertia. The framework independently allows accurate real-time measurement and control of engineered muscle tissue contraction in-vitro for heart failure drug discovery.

Date of Award	20 Jan 2026
Original language	English
Awarding Institution	University of Bristol
Supervisor	Jonathan M Rossiter (Supervisor), Andrew T Conn (Supervisor) & Fabrizio Scarpa (Supervisor)