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丝素蛋白/甲基纤维素基可注射水凝胶中掺入的磷酸钙:用于骨缺损治疗的制备、表征和体外生物学评价。

Calcium phosphate incorporated in silk fibroin/methylcellulose based injectable hydrogel: Preparation, characterization, and in vitro biological evaluation for bone defect treatment.

机构信息

Faculty of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Naresuan University, Phitsanulok, Thailand.

Faculty of Medicine, Department of Orthopaedics, Naresuan University, Phitsanulok, Thailand.

出版信息

J Biomed Mater Res B Appl Biomater. 2023 Sep;111(9):1640-1652. doi: 10.1002/jbm.b.35262. Epub 2023 May 17.

DOI:10.1002/jbm.b.35262
PMID:37194686
Abstract

Bone defect is still a challenging problem in orthopedic practice. Injectable bone substitutes that can fill different geometry of bone defect and improve biological environment for bone regeneration are attracting attention. Herein, silk fibroin (SF) is noticeable polymer regarding its biocompatible and biodegradable properties. Thus, the calcium phosphate particles incorporated in silk fibroin/methylcellulose (CAPs-SF/MC) and only methylcellulose (CAPs-MC) hydrogels are developed and compared their physicochemical properties. Both CAPs-hydrogels solutions can be administered with a low injectability force of ~6 N, and they require ~40-min to change to hydrogel at physiological temperature (37°C). The CAPs are evenly distributed throughout the hydrogel matrix and are capable transformed to bioactive hydroxyapatite at pH 7.4. The CAPs in CAPs-SF/MC have a smaller size than those in CAPs-MC. Moreover, CAPs-SF/MC exhibit gradual degradation, as prediction of the degradation mechanism by the Peppas-Sahlin model and show a greater ability to sustain CAPs release. CAPs-SF/MC has good biocompatibility with less cytotoxicity in a dose-dependent manner on mouse preosteoblast cell line (MC3T3-E1) when compared to CAPs-MC. CAPs-SF/MC hydrogels also have better possibility for promoting cell proliferation and differentiation. In conclusion SF incorporated into composite injectable hydrogel potentially improve biological characteristics and may provide clinical advantages.

摘要

骨缺损仍然是骨科实践中的一个具有挑战性的问题。可注射的骨替代物可以填充不同几何形状的骨缺损,并改善骨再生的生物环境,因此引起了人们的关注。在这里,丝素蛋白(SF)因其具有生物相容性和可生物降解性而引人注目。因此,开发了掺入丝素蛋白/甲基纤维素(CAPs-SF/MC)中的磷酸钙颗粒和仅甲基纤维素(CAPs-MC)水凝胶,并比较了它们的物理化学性质。两种 CAPs-水凝胶溶液都可以以约 6 N 的低注射力进行给药,并且在生理温度(37°C)下需要约 40 分钟才能转变为水凝胶。CAPs 均匀分布在水凝胶基质中,并能够在 pH 7.4 下转化为生物活性羟基磷灰石。CAPs-SF/MC 中的 CAPs 比 CAPs-MC 中的 CAPs 更小。此外,CAPs-SF/MC 表现出逐渐降解,根据 Peppas-Sahlin 模型预测的降解机制,并且具有更大的 CAPs 释放持续能力。与 CAPs-MC 相比,CAPs-SF/MC 对小鼠前成骨细胞系(MC3T3-E1)具有更好的生物相容性,并且具有剂量依赖性的更低的细胞毒性。CAPs-SF/MC 水凝胶还具有更好的促进细胞增殖和分化的可能性。总之,将 SF 掺入复合可注射水凝胶中可能会改善生物特性,并可能提供临床优势。

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