Development of a composite hydrogel incorporating anti-inflammatory and osteoinductive nanoparticles for effective bone regeneration.

IF 8.1 Q1 ENGINEERING, BIOMEDICAL
Hayeon Byun, Gyu Nam Jang, Hyewoo Jeong, Jinkyu Lee, Seung Jae Huh, Sangmin Lee, Eunhyung Kim, Heungsoo Shin
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引用次数: 0

Abstract

Background: Bone tissue regeneration is regulated by complex events, including inflammation, osteoinduction, and remodeling. Therefore, to induce the complete restoration of defective bone tissue, biomaterials with the ability to regulate the collective bone regenerative system are beneficial. Although some studies conclude that reducing reactive oxygen species created a favorable environment for bone regeneration by controlling inflammation, biomaterials that can simultaneously promote osteogenesis and regulate inflammation have not been developed. Herein, we describe the development of a multi-functional nanoparticle and its hydrogel composite with osteoinductive, anti-inflammatory, and osteoclast-maturation regulatory functions for enhanced bone regeneration.

Methods: Tannic acid-mineral nanoparticles (TMP) were prepared by self-assembly of tannic acid in an ion-rich simulated body fluid containing Ca2+ and PO43-. Particles with a diameter of 443 ± 91 nm were selected for their stable spherical morphology and minimal tendency to aggregate. The particles were homogeneously embedded within a gelatin-based cryogel (TMP/Gel) to be used in further experiments. The osteoinductive properties, anti-inflammatory and osteoclast-maturation regulatory functions in vitro were tested by culturing corresponding cells on either TMP/Gel or a gelatin-based cryogel without the particles (Gel). For in vivo analyses, a murine calvarial defect model was used. Statistical analyses were carried out using a Graphpad Prism 7 software (San Diego, CA, USA) to perform one-way analysis of variance ANOVA with Tukey's honest significant difference test and a Student's t-test (for two variables) (P < 0.05).

Results: Excellent biocompatibility and radical scavenging abilities were exhibited by the TMP/Gel. The expression of osteogenic mRNA is significantly increased in human adipose-derived stem cells seeded on the TMP/Gel compared to those without the particles. Furthermore, RAW264.7 cells seeded on the TMP/Gel displayed significantly lower-than-normal levels of pro-inflammatory and osteoclastogenic genes. Finally, the in vivo results indicated that, compared with the cryogel with no anti-inflammatory effect, the TMP/Gel significantly enhanced both the quality and quantity of newly formed bone, demonstrating the importance of combining anti-inflammation with osteoinduction.

Conclusion: Collectively, these findings suggest our nanoparticle-hydrogel composite could be an effective tool to regulate complex events within the bone healing process.

开发一种含有抗炎和骨诱导纳米粒子的复合水凝胶,以实现有效的骨再生。
背景:骨组织再生受炎症、骨诱导和重塑等复杂事件的调控。因此,要诱导缺损骨组织的完全恢复,具有调节集体骨再生系统能力的生物材料是有益的。尽管一些研究认为,减少活性氧可通过控制炎症为骨再生创造有利环境,但能同时促进骨生成和调节炎症的生物材料尚未开发出来。在此,我们介绍了一种多功能纳米粒子及其水凝胶复合材料的开发情况,该材料具有诱导骨生成、抗炎和破骨细胞成熟调节功能,可促进骨再生:单宁酸-矿物质纳米粒子(TMP)是通过单宁酸在含有 Ca2+ 和 PO43- 的富离子模拟体液中的自组装制备的。选择直径为 443 ± 91 nm 的颗粒是因为它们具有稳定的球形形态和最小的聚集倾向。这些颗粒被均匀地嵌入明胶基低温凝胶(TMP/Gel)中,以用于进一步的实验。通过在 TMP/Gel 或不含颗粒的明胶基冷凝胶(Gel)上培养相应的细胞,测试了其体外诱导骨生成特性、抗炎和破骨细胞成熟调节功能。体内分析则使用了小鼠腓骨缺损模型。统计分析使用 Graphpad Prism 7 软件(美国加利福尼亚州圣迭戈市)进行单向方差分析方差分析,并进行 Tukey 诚信显著差异检验和学生 t 检验(两个变量)(P 结果):TMP/Gel 具有良好的生物相容性和自由基清除能力。与不含颗粒的干细胞相比,播种在 TMP/Gel 上的人脂肪来源干细胞的成骨 mRNA 表达量明显增加。此外,播种在 TMP/Gel 上的 RAW264.7 细胞的促炎基因和破骨细胞生成基因水平明显低于正常水平。最后,体内研究结果表明,与没有抗炎作用的低温凝胶相比,TMP/凝胶能显著提高新形成骨的质量和数量,这表明了抗炎与诱导骨形成相结合的重要性:总之,这些研究结果表明,我们的纳米粒子-水凝胶复合材料可以成为调节骨愈合过程中复杂事件的有效工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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