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Biomater. Res., Dec 12 2023, 27 (1) | https://doi.org/10.1186/s40824-023-00473-9 Development of a composite hydrogel incorporating anti-inflammatory and osteoinductive nanoparticles for effective bone regeneration

Hayeon Byun^1,2†, Gyu Nam Jang^1,2†, Hyewoo Jeong^1,2†, Jinkyu Lee^1,2, Seung Jae Huh^1,2, Sangmin Lee^1,2, Eunhyung Kim^1,2 and Heungsoo Shin^1,2,3*

¹Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea

²Department of Bioengineering, BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea

³Institute of Nano Science and Technology, Hanyang University, 222 Wangsimri-ro, Seongdong- gu, Seoul 04763, Republic of Korea

^†Hayeon Byun, Gyu Nam Jang and Hyewoo Jeong contributed equally to this work.

^*Correspondence: Heungsoo Shin

Abstract

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. Tannic acid-mineral nanoparticles (TMP) were prepared by self-assembly of tannic acid in an ion-rich simulated body fluid containing Ca ²⁺ and PO ₄ ^3-. 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). 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. Collectively, these findings suggest our nanoparticle-hydrogel composite could be an effective tool to regulate complex events within the bone healing process.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-14)
연구진국내 연구진
분야 생명과학 > 생물공학

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