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.
Polyvinyl alcohol (PVA) hydrogels are extensively used as scaffolds for tissue engineering, although their biodegradation properties have not been optimized yet. To overcome this limitation, partially oxidized PVA has been developed by means of different oxidizing agents, obtaining scaffolds with improved biodegradability. The oxidation reaction also allows tuning the mechanical properties, which are essential for effective use in vivo. In this work, the compressive mechanical behavior of native and partially oxidized PVA hydrogels is investigated, to evaluate the effect of different oxidizing agents, i.e., potassium permanganate, bromine, and iodine. For this purpose, PVA hydrogels are tested by means of indentation tests, also considering the time-dependent mechanical response. Indentation results show that the oxidation reduces the compressive stiffness from about 2.3 N/mm for native PVA to 1.1 ÷ 1.4 N/mm for oxidized PVA. During the consolidation, PVA hydrogels exhibit a force reduction of about 40% and this behavior is unaffected by the oxidizing treatment. A poroviscoelastic constitutive model is developed to describe the time-dependent mechanical response, accounting for the viscoelastic polymer matrix properties and the flow of water molecules within the matrix during long-term compression. This model allows to estimate the long-term Young’s modulus of PVA hydrogels in drained conditions (66 kPa for native PVA and 34–42 kPa for oxidized PVA) and can be exploited to evaluate their performances under compressive stress in vivo, as in the case of cartilage tissue engineering.
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