Hybrid Tricalcium Phosphate/Hydrogel Constructs Functionalized with an Antitumor Drug for Bone Tissue Regeneration
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RIALS FOR ENSURING HUMAN VITAL ACTIVITY AND ENVIRONMENTAL PROTECTION
Hybrid Tricalcium Phosphate/Hydrogel Constructs Functionalized with an Antitumor Drug for Bone Tissue Regeneration P. A. Karalkina, *, N. S. Sergeyevaa, I. K. Sviridovaa, V. A. Kirsanovaa, S. A. Akhmedovaa, Ya. D. Shanskya, N. V. Leontyevb, D. M. Zuyevc, E. S. Klimashinab, P. V. Yevdokimovb, and V. I. Putlyaevb a
Moscow Oncology Research Center, National Medical Research Center of Radiology, Ministry of Health of Russia, Moscow, 125284 Russia b Department of Chemistry, Moscow State University, Moscow, 119991 Russia c Department of Materials Science, Moscow State University, Moscow, 119991 Russia *e-mail: [email protected] Received June 6, 2019; revised June 26, 2019; accepted June 27, 2019
Abstract—Hybrid materials designed for the regeneration of bone defects and consisting of a resorbable ceramic base (tricalcium phosphate, TCP) coated with a layer of hydrophilic biodegradable polymer have been developed. Biocompatibility of the ceramics was evaluated through in vitro tests using cultures of human skin fibroblasts. To increase the therapeutic potential, the created model structures were saturated with the antitumor drug doxorubicin within the composition of the coating of UV-polymerizable hydrogel based on polyacrylamide/polyethylene glycol diacrylate (PAA/PEGDA). The kinetics of drug release was studied by spectrophotometry using saline. The studied hybrid constructs had low cytotoxicity. Saturation of the structures with the antitumor drug resulted in its prolonged release. The results demonstrate the technological feasibility of creating osteoconductive implants based on calcium phosphates suitable for local delivery of antitumor drugs. Keywords: hybrid biomaterials, tricalcium phosphate, biodegradation, hydrogels, doxorubicin, local drug delivery DOI: 10.1134/S2075113320050160
INTRODUCTION Tissue engineering constructs (TECs) are used in regenerative methods of treatment to restore biological functions of the bone. Creation of TECs for the treatment of bone defects is especially important when the size of the defect exceeds the critical level and the body’s own capabilities are insufficient to restore bone tissue [1]. TECs are based on biodegradable porous matrices (scaffolds) populated by cells capable of bone formation. In recent years, the problem of targeted delivery of drugs to bone defects as part of TECs has been interdisciplinary as a result of the convergence of regional chemotherapy methods and additive technologies for the manufacture of scaffolds for tissue reconstruction of bone defects of various, including oncological, origin. The very concept of using such functionalized constructions is due to the widespread metastatic damage to bone tissue, the frequency of which reaches 65–75% for breast and prostate cancer, about 60% for thyroid cancer, and up to 40% for cases of lung and kidney cancer in patients with these nosologies [2]. The use of scaffolds filled with antitumor
drugs can significantly reduce the likelihood of me
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