A Novel Bioreactor for the Mechanical Stimulation of Clinically Relevant Scaffolds for Muscle Tissue Engineering Purposes

Silvia Spadoni,Silvia Todros,Edoardo Maghin,Piero G Pavan,Martina Piccoli

doi:10.3390/pr9030474

Silvia Spadoni, Silvia Todros + Show 3 more

Open Access

https://doi.org/10.3390/pr9030474

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Journal: Processes	Publication Date: Mar 7, 2021
Citations: 13	License type: CC BY 4.0

Affiliation: University of Padua, Città della Speranza Foundation

Abstract

Muscular tissue regeneration may be enhanced in vitro by means of mechanical stimulation, inducing cellular alignment and the growth of functional fibers. In this work, a novel bioreactor is designed for the radial stimulation of porcine-derived diaphragmatic scaffolds aiming at the development of clinically relevant tissue patches. A Finite Element (FE) model of the bioreactor membrane is developed, considering two different methods for gripping muscular tissue patch during the stimulation, i.e., suturing and clamping with pliers. Tensile tests are carried out on fresh and decellularized samples of porcine diaphragmatic tissue, and a fiber-reinforced hyperelastic constitutive model is assumed to describe the mechanical behavior of tissue patches. Numerical analyses are carried out by applying pressure to the bioreactor membrane and evaluating tissue strain during the stimulation phase. The bioreactor designed in this work allows one to mechanically stimulate tissue patches in a radial direction by uniformly applying up to 30% strain. This can be achieved by adopting pliers for tissue clamping. Contrarily, the use of sutures is not advisable, since high strain levels are reached in suturing points, exceeding the physiological strain range and possibly leading to tissue laceration. FE analysis allows the optimization of the bioreactor configuration in order to ensure an efficient transduction of mechanical stimuli while preventing tissue damage.

Highlights

Tissue engineering is one of the most dynamic and rapidly expanding fields in biomedical sciences
A novel bioreactor is designed for the radial stimulation of porcine-derived diaphragmatic scaffolds aiming at the development of clinically relevant tissue patches
Tissue engineering focuses on combining cells with supporting synthetic or naturally derived biomaterials that essentially act as scaffolds for tissue formation in vitro by allowing cells to adhere, proliferate, migrate, differentiate, and produce new tissue [1]

Summary

Introduction

Tissue engineering is one of the most dynamic and rapidly expanding fields in biomedical sciences. Mechanical stimulation regimens may be tuned in terms of loading direction, strain level, and time-dependent factors, such as loading–unloading frequency and rest period between subsequent strain cycles [11] The use of these protocols is complex and typically requires custom-designed bioreactors for specific biomaterial scaffolds and the chosen application. Many bioreactors provide a mechanical stimulation along a unique direction, allowing the development of oriented 3D muscle bundles that are often able to contract [12,13,14] This type of approach leads to in vitro production of constructs with aligned muscular fibers in a preferred direction, recapitulating the anatomy of most skeletal muscles. The development of bioreactors for biaxial or radial stimulation is less common in the literature [15]

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