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含纳米羟基磷灰石和骨形态发生蛋白的可注射交联透明质酸在小鼠颅骨上的骨形成

Bone Formation on Murine Cranial Bone by Injectable Cross-Linked Hyaluronic Acid Containing Nano-Hydroxyapatite and Bone Morphogenetic Protein.

作者信息

Hachinohe Yuki, Taira Masayuki, Hoshi Miki, Hatakeyama Wataru, Sawada Tomofumi, Kondo Hisatomo

机构信息

Department of Prosthodontics and Oral Implantology, School of Dentistry, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan.

Department of Biomedical Engineering, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho 028-3694, Japan.

出版信息

Polymers (Basel). 2022 Dec 8;14(24):5368. doi: 10.3390/polym14245368.

Abstract

New injection-type bone-forming materials are desired in dental implantology. In this study, we added nano-hydroxyapatite (nHAp) and bone morphogenetic protein (BMP) to cross-linkable thiol-modified hyaluronic acid (tHyA) and evaluated its usefulness as an osteoinductive injectable material using an animal model. The sol (ux-tHyA) was changed to a gel (x-tHyA) by mixing with a cross-linker. We prepared two sol−gel (SG) material series, that is, x-tHyA + BMP with and without nHAp (SG I) and x-tHyA + nHAp with and without BMP (SG II). SG I materials in the sol stage were injected into the cranial subcutaneous connective tissues of mice, followed by in vivo gelation, while SG II materials gelled in Teflon rings were surgically placed directly on the cranial bones of rats. The animals were sacrificed 8 weeks after implantation, followed by X-ray analysis and histological examination. The results revealed that bone formation occurred at a high rate (>70%), mainly as ectopic bone in the SG I tests in mouse cranial connective tissues, and largely as bone augmentation in rat cranial bones in the SG II experiments when x-tHyA contained both nHAp and BMP. The prepared x-tHyA + nHAp + BMP SG material can be used as an injection-type osteoinductive bone-forming material. Sub-periosteum injection was expected.

摘要

牙种植学领域需要新型注射型骨形成材料。在本研究中,我们将纳米羟基磷灰石(nHAp)和骨形态发生蛋白(BMP)添加到可交联的硫醇修饰透明质酸(tHyA)中,并使用动物模型评估其作为骨诱导性可注射材料的效用。通过与交联剂混合,溶胶(ux-tHyA)转变为凝胶(x-tHyA)。我们制备了两个溶胶-凝胶(SG)材料系列,即含和不含nHAp的x-tHyA + BMP(SG I)以及含和不含BMP的x-tHyA + nHAp(SG II)。将处于溶胶阶段的SG I材料注射到小鼠颅骨皮下结缔组织中,随后在体内凝胶化,而SG II材料在聚四氟乙烯环中凝胶化后通过手术直接放置在大鼠颅骨上。植入8周后处死动物,随后进行X射线分析和组织学检查。结果显示,当x-tHyA同时含有nHAp和BMP时,在小鼠颅骨结缔组织的SG I试验中骨形成发生率很高(>70%),主要为异位骨,而在SG II实验的大鼠颅骨中则主要为骨增量。所制备的x-tHyA + nHAp + BMP SG材料可作为注射型骨诱导性骨形成材料。预计可进行骨膜下注射。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e45/9783206/9068d99d0170/polymers-14-05368-g001.jpg

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