ABSTRACT
The purpose of this work was to determine the viscoelastic behavior of porcine and human oral mucosa under physiological conditions of temperature, hydration and chewing. The linear elastic and viscous shear moduli of these soft tissues were determined by small-amplitude oscillatory shear (SAOS) tests at masticatory frequency using a stress-controlled rheometer equipped with an immersion cell on punched biopsies 8 mm in diameter. Non physiological conditions of temperature were also used to access other parameters such as the denaturation temperature of collagen. First, the different parameters such as normal force, frequency and maximal strain were adjusted to obtain reliable data on porcine mucosa. The optimal normal force was 0.1N and the linear viscoelastic limit was found for a strain amplitude of 0.5% for both 0.1 and 1 Hz. The storage moduli of porcine mucosa, ranging from 5 to 16 kPa, were in the same range as cutaneous tissues determined by SAOS at equivalent frequencies. The storage modulus, superior to the loss modulus Gâ³, indicates a predominant elastic contribution to shear stress in chewing conditions. Second, this protocol evidenced an influence of the anatomic site of the mouth on the viscoelastic behavior of porcine mucosa, mandibular biopsies having higher storage moduli than maxillary biopsies. Temperature scans showed the mechanical manifestation of collagen denaturation in the 60-70 °C range as previous calorimetric analyses. Finally, this mechanical protocol was successfully adapted to characterize human mucosa in an elderly population. It was shown that the elastic modulus is impacted by local inflammation (gingivitis), decreasing significantly from 6 ± 1.4 kPa to 2.5 ± 0.3 kPa.
Subject(s)
Collagen , Mouth Mucosa , Aged , Humans , Animals , Swine , Elastic Modulus , Stress, Mechanical , Viscosity , ElasticityABSTRACT
Impairment of extracellular matrix remodeling is observed in the tumor microenvironment or fibrosis and results in excessive collagen production and/or decreased degradation by matrix metalloproteinases (MMPs). Thanks to their local application and transient effects, physical stimuli appear as attractive tools to remodel the extracellular matrix. We assessed the potential of pulsed electric field technology, classically applied to drug delivery, to induce collagen remodeling at the tissue scale. A sophisticated in vitro tissue-engineered human dermal substitute was used to show that microsecond and millisecond pulsed electric fields induced (i) a rapid modulation (4 hours after electrostimulation) of mRNA genes composing the matrisome, particularly a downregulation of procollagens and extracellular matrix maturation enzymes such as transglutaminase 2 and lysyl oxidase like; (ii) a transient decrease in procollagens production and hydroxyproline tissue content within a week after electrostimulation; (iii) a long-lasting ROS-dependent overactivation of matrix metalloproteinases for at least 48 hours; and (iv) a downregulation of TGFß1. These observations underpin that pulsed electric fields, a technology already approved for clinical use combined with anticancer agents, are particularly promising to provide local and effective treatment of abnormal extracellular matrix.
