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

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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



  1. Armiento A.R., Stoddart M.J., Alini M. et al. Biomaterials for articular cartilage tissue engineering: Learning from biology. Acta Biomater. 2018; 65:1-20.
  2. Varela-Eirin M., Loureiro J., Fonseca E. et al. Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis. Ageing Res Rev. 2018; 42:56-71.
  3. Van Bellinghen X., Idoux-Gillet Y., Pugliano M. et al. Temporomandibular Joint Regenerative Medicine. Int J. Mol Sci. 2018;19(2): 446.
  4. Xuan H., Hu H., Geng C. et al. Biofunctionalized chondrogenic shape-memory ternary scaffolds for efficient cell-free cartilage regeneration. Acta Biomater. 2020; 105:97-110.
  5. Xu X., Liang Y., Li X. et al. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials 2021; 269:120539.
  6. Helgeland E., Shanbhag S., Pedersen T.O. et al. Scaffold-based temporomandibular joint tissue regeneration in experimental animal models: a systematic review. Tissue Eng Part B. Rev. 2018; 24(4): 300-316.
  7. Johnstone B., Stoddart M.J., Im G.I. Multi-Disciplinary Approaches for Cell-Based Cartilage Regeneration. J. Orthop Res. 2020; 38(3): 463-472.
  8. Li T., Chen S., Pei M. Contribution of neural crest-derived stem cells and nasal chondrocytes to articular cartilage regeneration. Cell Mol Life Sci. 2020; 77(23): 4847-4859.
  9. Grol M.W., Lee B.H. Gene therapy for repair and regeneration of bone and cartilage. Curr Opin Pharmacol. 2018; 40:59-66.
  10. Li K.C., Hu Y.C. Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy. Adv Healthc Mater. 2015; 4(7): 948-68.
  11. Bougioukli S., Evans C.H., Alluri R.K. et al. Gene therapy to enhance bone and cartilage repair in orthopaedic surgery. Curr Gene Ther. 2018; 18(3): 154-170.
  12. Hamilton J.L., Nagao M., Levine B.R. et al. Targeting VEGF and its receptors for the treatment of osteoarthritis and associated pain. J. Bone Miner Res. 2016; 31(5): 911-924.
  13. Li Shan E. Fong, Casey K. Chan, Stuart B. Goodman. Stem Cells homing in musculoskeletal injury. Biomaterials 2011; 32(2): 395-409.
  14. Деев Р.В., Бозо И.Я., Мавликеев М.О. и др. Регенерационный гистогенез в области дефекта скелетной мышцы при местном введении ген-активированного гидрогеля на основе гиалуроновой кислоты в эксперименте. Гены и Клетки 2020; XV(2): 66-72. [Deev R.V., Bozo I.Y., Mavlikeev V.O. et al. Regenerative histogenesis in a skeletal muscle defect with local implantation of gene-activated hydrogel based on hyaluronic acid in the experiment. Genes & Cells 2020; 15(2): 66-72
  15. Deev R., Bozo I., Isaev A. et al. Results of 5-year follow-up study in patients with peripheral artery disease treated with PL-VEGF165 for intermittent claudication. Ther Adv Cardiovasc Dis. 2018;12(9): 237-246.
  16. Komlev V.S., Barinov S.M., Bozo 1.1. et al. Bioceramics composed of octacalcium phosphate demonstrate enhanced biological behavior. ACS Appl Mater Interfaces. 2014; 6(19): 16610-20.

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