Stiff substrates inhibit collagen accumulation via integrin α2ß1, FAK and Src kinases in human atrial fibroblast and myofibroblast cultures derived from patients with aortal stenosis.

The aim of the study was to confirm whether cell substrate stiffness may participate in the regulation of fibrosis. The involvement of integrin α2ß1, focal adhesion kinase (FAK) and Src kinase in signal transmission was investigated. Human atrial fibroblasts and myofibroblasts were cultured in both soft (2.23 ± 0.8 kPa) and stiff (8.28 ± 1.06 kPa) polyacrylamide gels. The cells were derived from the right atrium of patients with aortal stenosis undergoing surgery. The isolated cells, identified as fibroblasts or myofibroblasts, were stained positively with α smooth muscle actin, vimentin and desmin. The cultures settled on stiff gel demonstrated lower intracellular collagen and collagen type I telopeptide (PICP) levels; however, no changes in α1 chain of procollagen type I and III expression were noted. Inhibition of α2ß1 integrin by TC-I 15 (10-7 and 10-8 M) or α2 integrin subunit silencing augmented intracellular collagen level. Moreover, FAK or Src kinase inhibitors increased collagen content within the culture. Lower TIMP4 secretion was reported within the stiff gel cultures but neither MMP 2 nor TIMP-1, 2 or 3 release was altered. The stiff substrate cultures also demonstrated lower interleukin-6 release. Substrate stiffness modified collagen deposition within the atrial fibroblast and myofibroblast cultures. The elasticity of the cellular environment exerts a regulatory influence on both synthesis and breakdown of collagen. Integrin α2ß1, FAK and Src kinase activity participates in signal transmission, which may influence fibrosis in the atria of the human heart.

Evaluation of the healing process after implantation of synthetic material called Tegmentum consisting of polyester mesh covered with polyurethane in rat peritoneum.

Polyester meshes are one of the synthetic prosthetic materials widely applied for the reconstruction of abdominal layers in child and neonatal surgery, cardiosurgery or vascular surgery. Because of the lack or insufficiency of the own, natural material multiple researches are performed in order to find the best material able to replace natural tissue. The most suitable prosthesis ought to be: sterile, non-toxic, soft, flexible, elastic, not very stretchy, durable, easy to operate (cutting, suturing); to create desired shape required while reconstracting, totally resistant to contagion, without any complication after being implanted. Since early seventies many scientists following above requirements have carried out researches to create the most similar prosthesis morphologically and functionally to human tissue but still there is no such an ideal material on the market. Polyester with its derivatives is one of the most commonly applied synthetic substances in surgery. The type of biomaterial highly depends on its purpose e.g.: for vascular prosthesis materials that are resorptive in organism and support tightness (gelatine, albumin, collagen); while for temporal replacement abdominal layers with prosthesis the most suitable is impervious to systemic fluids bacteria etc material, that prevents penetrating the surface of prosthesis by surrounding tissues, adhesions with intestinum or other organs. Tegmentum is a material that posses these features. This is a polyester mesh covered with polyurethane on one side produced by Tricomed S.A. (Lódz). Tegmentum has already been applied to neonates with congenital eventration in Child and Neonatal Ward in the "Szpital Pomnik Matki Polki" hospital in Lódz.