Highly Filled Compositions Based on Alginate Gel and Fine Tricalcium Phosphate for 3D Printing of Tissue-Engineered Matr

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Highly Filled Compositions Based on Alginate Gel and Fine Tricalcium Phosphate for 3D Printing of Tissue-Engineered Matrices A. V. Mironova, *, O. A. Mironovaa, A. O. Mariyanatsa, V. S. Komlevb, **, I. V. Smirnovb, E. Y. Kananykhinac, ***, T. Kh. Fatkhudinovc, and V. K. Popova aFederal

Research Center Crystallography and Photonics, Russian Academy of Sciences, Moscow, 119333 Russia Baikov Institute of Metallurgy and Materials Science, Russian Academy of Sciences, Moscow, 119334 Russia c Research Institute of Human Morphology, Moscow, 117418 Russia *e-mail: [email protected] **e-mail: [email protected] ***e-mail: [email protected]

b

Received August 10, 2019; revised September 12, 2019; accepted September 13, 2019

Abstract—In order to obtain hydrogel matrices for bone tissue engineering, the process of formation of highly filled alginate-calcium phosphate structures by 3D printing was developed. Optimal conditions for the formation of three-dimensional structures from Ca2+ crosslinked alginate hydrogels and highly filled alginate compositions with fine (5–30 μm) α-tricalcium phosphate (TCP) were determined. Comparative analysis of physicomechanical properties of crosslinked alginate hydrogels showed lower strength and higher elastic modulus of the TCP-filled composite in comparison with pure hydrogel. The difference between the mechanical characteristics of the filled and pure gels increases with the crosslinking density. It was found that, because of the significant content of the mineral dispersed phase, the α-TCP-filled hydrogel does not shrink during crosslinking, unlike pure alginate hydrogel. Using cultures of human umbilical cord mesenchymal stem cells, it was shown in vitro that all the studied samples of both pure and highly filled composite alginate matrices with α-TCP do not have short-term cytotoxic effects. Keywords: tissue engineering, 3D printing, hydrogel, alginate, α-tricalcium phosphate DOI: 10.1134/S2075113320050214

INTRODUCTION One of the fundamental approaches to solving the problem of restoring damaged or lost bone fragments is the use of tissue engineering constructs (TECs) [1]. The key elements of such structures are biocompatible (usually bioresorbable) bulk porous scaffolds (matrices) of a given shape, size, and internal structure [2], which provide effective primary adhesion, proliferation, and differentiation of cell cultures in the presence of required bioactive components (growth factors, enzymes, etc.) [3]. Ideally, such a matrix should have a certain set of biochemical, physicochemical, and structural characteristics. These primarily include no cytotoxicity, osteogenic potential, controllable rates of resorption or degradation in biologically active media, highly developed structure including a system of interpenetrating pores of various sizes for effective cell attachment and growth and transport of intercellular fluid, and mechanical properties similar to characteristics of bone tissue of the required type. I