Bioresorbable porous β-tricalcium phosphate chelate-setting cements with poly(lactic-co-glycolic acid) particles as pore-forming agent: fabrication, material properties, cytotoxicity, and in vivo evaluation

Akihiro Ando; Maho Kamikura; Yuko Takeoka; Masahiro Rikukawa; Kazuaki Nakano; Masaki Nagaya; Hiroshi Nagashima; Mamoru Aizawa

doi:10.1080/14686996.2021.1936628

Bioresorbable porous β-tricalcium phosphate chelate-setting cements with poly(lactic-co-glycolic acid) particles as pore-forming agent: fabrication, material properties, cytotoxicity, and in vivo evaluation

Sci Technol Adv Mater. 2021 Jun 24;22(1):511-521. doi: 10.1080/14686996.2021.1936628.

Authors

Akihiro Ando¹, Maho Kamikura¹, Yuko Takeoka², Masahiro Rikukawa², Kazuaki Nakano³, Masaki Nagaya³, Hiroshi Nagashima^{3

4}, Mamoru Aizawa^{1

5}

Affiliations

¹ Department of Applied Chemistry, School of Science and Technology, Meiji University, Kanagawa, Japan.
² Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, Tokyo, Japan.
³ Meiji University International Institute for Bio-Resource Research, Meiji University, Kanagawa, Japan.
⁴ Department of Life Sciences, School of Agriculture, Meiji University, Kanagawa, Japan.
⁵ Meiji University International Institute for Materials with Life Functions, Meiji University, Kanagawa, Japan.

Abstract

Calcium-phosphate cements (CPCs) have been used as bone filling materials in orthopaedic surgery. However, CPCs are set using an acid-base reaction, and then change into stable hydroxyapatite (HAp) in a living body. Therefore, we developed bioresorbable chelate-setting β-tricalcium phosphate (β-TCP) cements based on surface modifications of inositol phosphate (IP6). In order to improve the bioresorbability, we fabricated IP6/β-TCP cements hybridized with poly(lactic-co-glycolic acid) (PLGA) particles as a pore-forming agent. The compressive strengths of the cements with the amounts of 5 and 10 mass% PLGA particles were 23.2 and 22.8 MPa, respectively. There was no significant difference from cements without PLGA (23.4 MPa). The setting times of the cement specimens with PLGA particles (30 min) were a little longer than those without PLGA particles (26.3 min). The lack of cytotoxicity of the cement specimens was confirmed using osteoblast-like cells (MC3T3-E1). Cylindrical defects were made by drilling into the tibia of mini-pigs and injecting the prepared cement pastes into the defects. Twelve weeks after implantation the specimens were stained with toluidine blue and histologically evaluated. Histological evaluation of cement specimens with PLGA particles showed enhanced bioresorbability. Newly-formed bone was also observed inside cement specimens with PLGA particles. The IP6/β-TCP cement specimens with PLGA particles had excellent material properties, such as injectability, compressive strength, high porosity, no cytotoxicity in vitro, bioresorption and bone formation abilities in vivo. Organic-inorganic hybridized CPCs are expected to be valuable as novel biodegradable paste-like artificial bone fillers.

Keywords: 30 Bio-inspired and biomedical materials; bioresorbability; calcium-phosphate cement; chelate-setting cement; mechanical property; poly(lactic-co-glycolic acid) particles; β-tricalcium phosphate.

Grants and funding

This research is supported by Private Universities Foundation for the Development of Fundamental Research Strategies (Project: Development of Next-generation Regenerative Medicine Process Using Biomaterials with Life Function on the Basis of Vertical Integration System), Ministry of Education, Culture, Sports, Science and Technology, Japan.