Short Stimulation of Electro-Responsive PAA/Fibrin Hydrogel Induces Collagen Production

Abstract

Acrylic acid/fibrin hydrogel can mechanically stimulate cells when an external electrical field is applied, enabling them to migrate and align throughout the depth of the gel. The ability of electro-responsive polyacrylic acid (PAA)/fibrin hydrogel to promote collagen production and remodeling has been investigated by threedimensional (3D) culturing and conditioning of smooth muscle cells (SMCs). SMCs-seeded hydrogels were subjected to an alternating electrical field (0.06 V/mm) for 2 h for one, two, or three times per week during 4 weeks of culturing. Fluorescent images of collagen structure and accumulation, assessed by CNA-35 probe, showed increased collagen content ( > 100-fold at 1· stimulation/week) in the center of the hydrogels after 4 weeks of culture. The increase in collagen production correlated with increasing extracellular matrix gene expression and resulted in significantly improved mechanical properties of the stimulated hydrogels. Matrix metalloproteinase (MMP)-2 activity was also significantly enhanced by stimulation, which probably has a role in the reorganization of the collagen. Short stimulation (2 h) induced a favorable response in the cells and enhanced tissue formation and integrity of the scaffold by inducing collagen production. The presented set up could be used for conditioning and improving the functionality of current tissue-engineered vascular grafts.

Phosphodiester Hydrogels for Cell Scaffolding and Drug Release Applications

“…Furthermore, pronounced α‐smooth muscle actin expression ( Figure 5 B), collagen synthesis (Figure 5 C) and colonization (Figure A,D) by SMCs showed poly(phosphodiester) hydrogels to be suitable matrices for supporting tissue growth and development. When comparing the performance of the hydrogel presented in this paper concerning the cell performance with an earlier described poly‐acrylic acid (PAA) hydrogel, there can be concluded that cell distribution within the phosphodiester hydrogel is comparable with or even extends that of the PAA hydrogel (in control conditions). In the upper layers, cell distribution is comparable between gel types, but in subsuperficial layers, cell density drops more rapidly in PAA than in phosphodiester hydrogels.…”

Engineering of Human Skeletal Muscle With an Autologous Deposited Extracellular Matrix

“…Other methods to increase collagen deposition may be utilized in parallel to or instead of stimulation by ascorbic acid. For example, addition of fibrin degradation products ( Ahmann et al, 2010 ) and electrical stimulation ( Rahimi et al, 2014 ) have been shown to enhance collagen deposition. Furthermore, ascorbic acid has a toxic effect at higher concentration, but magnesium ascorbyl phosphate, a stable derivative of ascorbic acid, was shown to be usable at higher concentrations with human tenocytes ( Hakimi et al, 2014 ).…”

Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management

“…In vitro and in vivo studies displayed a pulsatile drug release profile after an applied electric field. Biocompatible electroresponsive hydrogels composed of polyacrylic acid and fibrin were found to stimulate cell growth and tissue formation [ 32 ].…”