Regenerative histogenesis in a skeletal muscle defect with local implantation of gene-activated hydrogel based on hyaluronic acid in the experiment



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Abstract

Optimization of the reparative regeneration of striated skeletal muscle tissue is actual for clinical practice. Volumetric muscle loss usually heals through the fibrous scar formation. Herein, there are numerous of methods under developed focused on reparative myogenesis induction. One of the promising approaches in this area is formed by gene-activated materials, particularly, in the hydrogel form. We developed a gene-activated hydrogel based on hyaluronic acid and plasmid DNA with the gene of vascular endothelial growth factor A (VEGF-A). Firstly, we showed a biocompatibility of the product in the subcutaneous test in mice. Using marker plasmid DNA carrying the luciferase gene, prolonged delivery of gene constructs to cells in vivo with a peak in transgene expression at day 7 was confirmed, while the same plasmid DNA in an aqueous solution provided a maximum level of delivery at day 1. Being implanted into a volumetric defect of the anterior tibial muscle in rats the gene-activated hydrogel activated angiogenesis in 2 weeks after surgery and induced MYH7B+-muscle fibers formation in the central zone of the defect at average number 50,0±16,1 and 21,8±10,5 in 2 and 4 weeks, respectively, whereas a hydrogel without plasmid DNA did not have any myogenic effects. Thus, plasmid DNA with VEGFA in the sodium alginate-based hydrogel induced angiogenesis in the volumetric muscle loss model and stimulated reparative myogenesis that could be used for further development of products effective for treatment of patients with muscle pathology.

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About the authors

R. V Deev

I.I. Mechnikov North-Western State Medical University; Institute of Human Stem Cells PJSC; Histograft LLC

Email: romdey@gmail.com
Saint Petersburg, Russia; Moscow, Russia; Moscow, Russia

I. Y Bozo

Histograft LLC; Research Institute of General Pathology and Pathophysiology; A.I. Burnazyan Federal Medical Biophysical Center FMBA of Russia

Moscow, Russia; Moscow, Russia; Moscow, Russia

M. O Mavlikeev

Kazan (Volga region) Federal University

Kazan, Russia

A. I Bilyalov

Kazan (Volga region) Federal University

Kazan, Russia

A. A Titova

Kazan (Volga region) Federal University

Kazan, Russia

F. A Indeykin

Kazan Federal Medical University

Kazan, Russia

A. R Babkova

Kazan (Volga region) Federal University

Kazan, Russia

E. V Presnyakov

I.P. Pavlov Ryazan State Medical University

Ryazan, Russia

M. I Yasinovsky

Research Institute of General Pathology and Pathophysiology

Moscow, Russia

V. O Trofimov

Histograft LLC; A.I. Burnazyan Federal Medical Biophysical Center FMBA of Russia

Moscow, Russia

O. V Baranov

A.A. Baikov Institute of Metallurgy and Materials Science Russian Academy of Sciences

Moscow, Russia

I. A Odintsova

S.M. Kirov Military Medical Academy

Saint-Petersburg, Russia

V. S Komlev

A.A. Baikov Institute of Metallurgy and Materials Science Russian Academy of Sciences

Moscow, Russia

A. A Isaev

Institute of Human Stem Cells PJSC

Moscow, Russia

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