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羟基磷灰石-胶原纳米粒子增强聚酸酐基可注射糊剂用于骨替代:掺杂剂添加的影响。

Hydroxyapatite-collagen nanoparticles reinforced polyanhydride based injectable paste for bone substitution: effect of dopant addition .

机构信息

Department of Ceramic Engineering, NIT Rourkela, Rourkela, Odisha, India.

Department of Biotechnology and Medical Engineering, NIT Rourkela, Rourkela, Odisha, India.

出版信息

J Biomater Sci Polym Ed. 2021 Jul;32(10):1312-1336. doi: 10.1080/09205063.2021.1916867. Epub 2021 Jun 1.

DOI:10.1080/09205063.2021.1916867
PMID:33874849
Abstract

The present study focuses on the synthesis and characterization of hydroxyapatite-collagen nanoparticles incorporated polyanhydride paste and investigating its bone regeneration capacity . Photocrosslinkable polyanhydride paste was prepared after synthesizing methacrylate derivatives of 1,6-bis(p-carboxyphenoxy)hexane (MCPH) and sebacic acid dimethacrylate (MSA). These multifunctional monomers, namely 45 wt% MSA, 45 wt% MCPH in addition to 10 wt% poly(ethylene glycol)diacrylate (PEGDA) were photopolymerized under ultraviolet light (365 nm) to produce highly crosslinked polyanhydride networks using camphroquinone (CQ)/ethyl 4-(dimethylamino)benzoate [4-EDMAB] for light initiated crosslinking and benzoyl peroxide (BPO)/dimethyl toludine (DMT) for chemically initiated crosslinking. Separately, using the co-precipitation process, (1 wt%) Si, (1 wt%) Sr, and (0.5 + 0.5) wt% Si/Sr was doped into hydroxyapatite-collagen nanoparticles in size range between 50 and 70 nm. Si, Sr, and both Si/Sr doped hydroxyapatite-collagen nanoparticles to the extent 10 wt% were added to polyanhydride monomer mixture containing 40 wt% MSA, 40 wt% MCPH and 10 wt% PEGDA and subsequently photopolymerized as previously mentioned. Incorporation of hydroxyapatite-collagen nanoparticles to the extent of 10 wt% into polyanhydride matrix enhanced compressive strength of the hardened paste from 30 to 49 MPa. Mesenchymal stem cells obtained from the human umbilical cord were cultured onto pure polyanhydride and hydroxyapatite-collagen added scaffold to assess their cellular proliferation and differentiation capacity to bone cell. MTT assay showed that mesenchymal stem cell proliferation was significantly higher in Si/Sr binary doped hydroxyapatite-collagen-polyanhydride sample as compared to other samples. Again from immunocytochemistry study using confocal images suggested that expression of osteocalcin, a marker indicating differentiation into osteoblast, was the highest in Si/Sr binary doped hydroxyapatite-collagen-polyanhydride sample against the other samples studied in this case. This study thus summarizes the development of photocurable biocomposites containing polyanhydride and Si, Sr doped hydroxyapatite-collagen nanoparticles that exhibited tremendous promise to regenerate bone tissues in complex-shaped musculoskeletal defect sites.

摘要

本研究专注于合成和表征羟磷灰石-胶原纳米粒子掺入聚酸酐糊剂,并研究其骨再生能力。在合成甲基丙烯酸衍生物 1,6-双(对羧基苯氧基)己烷(MCPH)和癸二酸二甲基丙烯酸酯(MSA)后,制备了可光交联的聚酸酐糊剂。这些多功能单体,即 45wt%MSA、45wt%MCPH 以及 10wt%聚乙二醇二丙烯酸酯(PEGDA),在 365nm 紫外光下光聚合,以产生高度交联的聚酸酐网络,使用樟脑醌(CQ)/乙基 4-(二甲氨基)苯甲酸酯 [4-EDMAB] 进行光引发交联和过氧化二苯甲酰(BPO)/二甲基对甲苯胺(DMT)进行化学引发交联。另外,通过共沉淀法,将(1wt%)Si、(1wt%)Sr 和(0.5+0.5)wt%Si/Sr 掺杂到尺寸在 50 至 70nm 之间的羟磷灰石-胶原纳米粒子中。将 Si、Sr 以及 Si/Sr 掺杂的羟磷灰石-胶原纳米粒子添加到含有 40wt%MSA、40wt%MCPH 和 10wt%PEGDA 的聚酸酐单体混合物中,并按照上述方法进行光聚合。将羟磷灰石-胶原纳米粒子掺入聚酸酐基质中 10wt%,可将硬化糊剂的抗压强度从 30MPa 提高到 49MPa。从人脐带中获得的间充质干细胞被培养在纯聚酸酐和添加羟磷灰石-胶原的支架上,以评估其向成骨细胞的细胞增殖和分化能力。MTT 测定表明,与其他样品相比,Si/Sr 双掺羟磷灰石-胶原-聚酸酐样品中的间充质干细胞增殖显著更高。同样,从共聚焦图像的免疫细胞化学研究表明,成骨细胞分化的标志物骨钙素的表达在 Si/Sr 双掺羟磷灰石-胶原-聚酸酐样品中最高,而在本研究中研究的其他样品中则较低。因此,本研究总结了含有聚酸酐和 Si、Sr 掺杂羟磷灰石-胶原纳米粒子的光固化生物复合材料的开发,该复合材料有望在复杂形状的肌肉骨骼缺损部位再生骨组织。

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