Chondrogenesis induced in vivo by gene-activated hydrogel based on hyaluronic acid and plasmid DNA encoding VEGF


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Abstract

Development of effective methods for cartilage tissue repair is highly relevant for surgical practice. One of the promising approaches in this area is the use of gene-activated materials that capable to change the production of certain factors involved in reparative chondrogenesis regulation in the damaged area within a certain time. In this study, we developed two gene-activated hydrogels based on hyaluronic acid delivering plasmid DNA encoding vascular endothelial growth factor (VEGF-A) gene. One of the hydrogels also contained octacalcium phosphate microgranules. The materials were implanted into the defects of cranial bones, articular and auricle cartilages in rabbits. Control groups consisted of the same materials without plasmid DNA. We found that gene-activated materials formed a larger volume of cartilaginous tissue with complete restoration of the auricle by 90 days. Healing of the articular cartilage and subchondral bone was also more efficient at the 30 and 60 days follow-up, but by 90 days, remodeling of the newly formed cartilage into fibroelastic and fibrous connective tissues was observed in all groups. Cranial bone defects were filled with newly formed bone tissue in the test group by day 90, while in the control a residual defect filled by fibrous connective tissue was retained. Thus, developed variants of the gene-activated hydrogels are promising candidates to be medical devices for treatment of patients with bone and cartilage pathology.

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About the authors

E. V Presnyakov

I.I. Mechnikov North-Western State Medical University

E. S Rochev

First I.P. Pavlov Saint Petersburg Medical University

V. V Tserceil

I.I. Mechnikov North-Western State Medical University

M. P Nikitina

A.P. Avtsyn Research Institute of Human Morphology

E. Yu Kananykhina

A.P. Avtsyn Research Institute of Human Morphology

M. O Mavlikeev

I.I. Mechnikov North-Western State Medical University

T. S Chauzova

Research Institute of General Pathology and Pathophysiology

A. P Petrikina

Research Institute of General Pathology and Pathophysiology

I. I Eremin

Research Institute of General Pathology and Pathophysiology; National Research Center “Kurchatov Institute"

A. A Pulin

National Research Center “Kurchatov Institute"; N.I. Pirogov National Medical and Surgical Center

A. A Isaev

Institute of Human Stem Cells, PJSC

V. S Komlev

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

T. Kh Fatkhutdinov

A.P. Avtsyn Research Institute of Human Morphology

R. V Deev

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

I. Y Bozo

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

Email: bozo.ilya@gmail.com

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