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含生物活性磷酸钙的聚氨酯二甲基丙烯酸酯基复合材料的体外骨免疫反应:聚甲基丙烯酸甲酯骨水泥的潜在替代品

In Vitro Osteo-Immunological Responses of Bioactive Calcium Phosphate-Containing Urethane Dimethacrylate-Based Composites: A Potential Alternative to Poly(methyl methacrylate) Bone Cement.

作者信息

Singhatanadgit Weerachai, Sungkhaphan Piyarat, Thavornyutikarn Boonlom, Kitpakornsanti Setthawut, Young Anne, Janvikul Wanida

机构信息

Faculty of Dentistry and Research Unit in Mineralized Tissue Reconstruction, Thammasat University (Rangsit Campus), Pathum-thani 12121, Thailand.

National Metal and Materials Technology Center, National Science and Technology Development Agency, Khlong Luang 12120, Thailand.

出版信息

ACS Mater Au. 2024 Jul 18;4(6):612-627. doi: 10.1021/acsmaterialsau.4c00037. eCollection 2024 Nov 13.

Abstract

This investigation developed new composite bone cements using urethane dimethacrylate (UDMA), poly(propylene glycol) dimethacrylate (PPGDMA), and hydroxyethyl methacrylate (HEMA), with micrometer-sized aluminosilicate glass filler. Monocalcium phosphate monohydrate (MCPM) and hydroxyapatite (HA) particles were added to enhance biological performance, particularly osteo-immunomodulation. Free radical polymerization was triggered by mixing two pastes containing either benzoyl peroxide (BPO, an initiator) or N-tolyglycine glycidyl methacrylate (NTGGMA, an activator). Increasing butylated hydroxytoluene (BHT, an inhibitor) enabled a suitable delay after mixing at 25 °C for placement. At 37 °C, the delay time was reduced and the final conversion was enhanced. Findings also demonstrated the biocompatibility of the developed bone cement toward osteo-immunological cell lineages, including mesenchymal stem cells (MSCs), fibroblasts, osteoclast precursor RAW 246.7 cells, and peripheral blood mononuclear cells (PBMCs). Notably, the cement with both MCPM and HA combined facilitated sufficient MSC growth, enabling subsequent mineralization while concurrently suppressing the proliferation of fibroblasts, osteoclast progenitors, and PBMCs. Furthermore, composite cement exhibited the capacity to differentially regulate osteoblast differentiation, cell-(in)dependent mineralization, osteoclastogenesis, and PBMC-mediated inflammatory responses at both cellular and molecular levels in vitro. These observations suggested their potential use for bone repair, especially in cases of inflammation-associated bone defects.

摘要

本研究开发了新型复合骨水泥,其采用了二甲基丙烯酸聚氨酯(UDMA)、二甲基丙烯酸聚丙二醇酯(PPGDMA)和甲基丙烯酸羟乙酯(HEMA),并添加了微米级的硅铝酸盐玻璃填料。添加了一水磷酸二氢钙(MCPM)和羟基磷灰石(HA)颗粒以增强生物学性能,特别是骨免疫调节能力。通过混合两种分别含有过氧化苯甲酰(BPO,一种引发剂)或N-甲苯基甘氨酸甲基丙烯酸缩水甘油酯(NTGGMA,一种活化剂)的糊剂引发自由基聚合反应。增加丁基化羟基甲苯(BHT,一种抑制剂)可在25℃混合后实现合适的放置延迟时间。在37℃时,延迟时间缩短,最终转化率提高。研究结果还证明了所开发的骨水泥对包括间充质干细胞(MSC)、成纤维细胞、破骨细胞前体RAW 246.7细胞和外周血单核细胞(PBMC)在内骨免疫细胞谱系具有生物相容性。值得注意的是,同时含有MCPM和HA的骨水泥促进了MSC的充分生长,使其能够随后矿化,同时抑制成纤维细胞、破骨细胞祖细胞和PBMC的增殖。此外,复合骨水泥在体外细胞和分子水平上均表现出对成骨细胞分化、细胞(非)依赖性矿化、破骨细胞生成以及PBMC介导的炎症反应进行差异调节的能力。这些观察结果表明它们在骨修复方面具有潜在用途,尤其是在与炎症相关的骨缺损病例中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5740/11565289/f1cb5727fc14/mg4c00037_0001.jpg

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