Electrospun hollow fibres for muscle tissue engineering in a soft bioreactor chamber

Muscle tissue engineering involves the use of biomaterials, cells, and bioreactor systems to generate functional muscle tissue constructs. This field holds great promises for the development of in vitro models, which could have many applications in drug development and drug screening as well as for the study of developmental and pathophysiological processes. The development of reliable and clinically applicable in vitro tissue constructs would drastically reduce the number of animals that are being used in biological and medical research or for preclinical studies.

One of the challenges in the field is the diffusion limit which impedes gas and nutrient exchange in thicker constructs. This represents a particularly important aspect for muscle tissue engineering due to the tissue’s high metabolic demands. Another limiting factor is the application of appropriate external mechanical stimulation to support the maturation of developing tissues. Specifically, muscle tissue is known to significantly rely on mechanical input for growth and maturation. These challenges need to be addressed in order to create reliable and clinically relevant tissue constructs with enhanced structural integrity and functionality.

This project aims to address both challenges through the development of a soft bioreactor module that hosts flexible hollow fibres. Our research group has recently developed hollow electrospun fibres for vascular tissue engineering and a unique flexible bioreactor chamber that can undergo stimulation by humanoid robots. Together, those 2 technologies could provide an improved environment to support the synthesis of large and functional skeletal muscle tissue constructs.

This will be achieved through the following objectives:

1. Develop suitable electrospun hollow fibres
2. Redesign the soft chamber for hosting the hollow fibres
3. Carry out the bioreactor experiments with mechanical loading applied by a robotic shoulder
4. Assess the functionality of healthy & diseased constructs
5. Validate and explore the platform for testing drugs leading to tissue repair

From a 3R's perspective, such an advanced in vitro platform could significantly reduce the number of animals currently used in muscle research to study the molecular mechanisms of human developmental and pathological processes and to assess the efficacy and safety of new therapies, including new drugs and medical devices. We anticipate enhanced clinical applicability compared to animal models based on improved relevance to human physiology. If successful, this will ensure a wide uptake of the new in vitro platform and a subsequent reduction of animal used in the field.