Experimental study on the effects of a novel bone graft material based on poly(3-hydroxybutyrate) and simvastatin on bone formation

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Abstract

BACKGROUND: In surgical dentistry and maxillofacial surgery, no currently available bone graft material reliably provides predictable outcomes for the treatment of jawbone defects. Given the increasing number of patients with alveolar bone atrophy and post-traumatic jaw defects, the development of new materials with osteoinductive properties remains highly relevant, underscoring the importance of research in bone tissue engineering.

AIM: To assess the osteoinductive potential of a novel bone graft material based on poly(3-hydroxybutyrate) loaded with simvastatin in an in vivo sheep model.

METHODS: A single-center, prospective, comparative study was conducted between December 2022 and June 2023, involving 24 healthy sheep weighing 65–70 kg and aged 18–24 months. Strict inclusion and exclusion criteria ensured group homogeneity. Under general and local anesthesia, a lateral window approach to the maxillary sinus was performed to create a bony window for implantation. Group 1 received simvastatin-loaded poly(3-hydroxybutyrate) granules; group 2 received the same material without simvastatin. The primary outcome was the presence of morphological signs of osteoinduction, including the formation of new bone tissue. Secondary outcomes included morphometric assessment of structural bone parameters, such as the relative volume of newly formed bone and osteogenic activity.

RESULTS: Assessments were performed at 3 and 6 months post-implantation. At 3 months, granules of the bone graft material in group 1 were surrounded by moderate connective tissue and multiple foci of active osteogenesis around the simvastatin-loaded granules. In group 2, connective tissue predominated around the implanted granules, with isolated osteogenic foci. At 6 months, group 1 exhibited reduced connective tissue, persistent osteogenic foci, and predominantly mature lamellar bone. Histomorphometric analysis revealed that the relative volume of newly formed bone in the simvastatin group was 34.5% at 3 months and 63.4% at 6 months, significantly exceeding that of the control group (21.4 and 36.8%, respectively).

CONCLUSION: Simvastatin-loaded poly(3-hydroxybutyrate) granules significantly enhance bone formation. However, the long-term effects of simvastatin application require further investigation.

About the authors

Karina M. Salekh

Peoples' Friendship University of Russia

Author for correspondence.
Email: ms.s.karina@mail.ru
ORCID iD: 0000-0003-4415-766X
SPIN-code: 1798-1439
Russian Federation, Moscow

Alexey V. Volkov

Peoples' Friendship University of Russia

Email: volkov-av@rudn.ru
ORCID iD: 0000-0002-5611-3990
SPIN-code: 1126-1347

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Alexander A. Muraev

Peoples' Friendship University of Russia

Email: muraev_aa@pfur.ru
ORCID iD: 0000-0003-3982-5512
SPIN-code: 1431-5936

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Anton P. Bonartsev

Lomonosov Moscow State University; Fundamentals of Biotechnology Federal Research Centre of the Russian Academy of Sciences

Email: ant_bonar@mail.ru
ORCID iD: 0000-0001-5894-9524
SPIN-code: 1688-2226

Dr. Sci. (Biology), Associate Professor

Russian Federation, Moscow; Moscow

Vera V. Voinova

Lomonosov Moscow State University

Email: veravoinova@mail.ru
ORCID iD: 0000-0002-0253-6461
SPIN-code: 6293-0462

Cand. Sci. (Biology)

Russian Federation, Moscow

Alexander B. Dymnikov

Peoples’ Friendship University of Russia

Email: dymnikov_ab@pfur.ru
ORCID iD: 0000-0001-8980-6235
SPIN-code: 7254-4306

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, Moscow

Alexander A. Dolgalev

Stavropol State Medical University

Email: dolgalev@dolgalev.pro
ORCID iD: 0000-0002-6352-6750
SPIN-code: 5941-5771

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Stavropol

Sergey Yu. Ivanov

Peoples’ Friendship University of Russia; Sechenov First Moscow State Medical University

Email: syivanov@yandex.ru
ORCID iD: 0000-0001-5458-0192
SPIN-code: 2607-2679

MD, Dr. Sci. (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Moscow; Moscow

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2. Fig. 1. Bone regenerate from the floor of the maxillary sinus containing rounded granules of osteoplastic material around which both immature (reticulofibrous) and mature (lamellar) bone tissue is formed in the presence of simvastatin (a); without simvastatin inclusion, predominantly immature bone tissue (b). Haematoxylin and eosin staining.

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3. Fig. 2. Bone regenerate from the floor of the maxillary sinus containing rounded granules of osteoplastic material around which mature (lamellar) bone tissue forms in the presence of simvastatin occupies a larger regenerate space around the material (a); without simvastatin inclusion, a small amount of predominantly lamellar bone tissue (b). Haematoxylin and eosin staining.

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