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.

摘要

磷酸钙骨水泥 (CPC) 已被用作骨科手术中的骨填充材料。然而，CPC 是通过酸碱反应固化的，然后在生物体内转变为稳定的羟基磷灰石 (HAp)。因此，我们开发了基于磷酸肌醇 (IP6) 表面改性的生物可吸收螯合固定β-磷酸三钙 ( β -TCP) 水泥。为了提高生物可吸收性，我们制造了 IP6/ β-TCP 水泥与作为成孔剂的聚（乳酸-乙醇酸共聚物）（PLGA）颗粒混合。含有 5 质量％和 10 质量％PLGA 颗粒的水泥的抗压强度分别为 23.2 和 22.8 MPa。与不含 PLGA (23.4 MPa) 的水泥没有显着差异。含有 PLGA 颗粒的水泥试样的凝结时间（30 分钟）比不含 PLGA 颗粒的水泥试样（26.3 分钟）稍长。使用成骨细胞样细胞 (MC3T3-E1) 证实了水泥样品没有细胞毒性。通过钻入小型猪的胫骨并将制备的水泥浆注入缺陷中来制造圆柱形缺陷。植入后十二周，标本用甲苯胺蓝染色并进行组织学评估。具有 PLGA 颗粒的水泥标本的组织学评估显示增强的生物再吸收性。在含有 PLGA 颗粒的水泥标本中也观察到了新形成的骨骼。IP6/β -TCP水泥标本PLGA颗粒具有优异的材料性质，如可注射，压缩强度，高的孔隙率，无细胞毒性在体外，生物再吸收和骨形成的能力在体内。有机-无机杂交 CPC 有望作为新型可生物降解的糊状人工骨填充剂。