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Bioact. Mater., 2024 Mar 5:36:185-202 | https://doi.org/10.1016/j.bioactmat.2024.02.029 Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization

Hayeon Byun ^a,b,1, Yujin Han ^a,1, Eunhyung Kim ^a, Indong Jun ^c, Jinkyu Lee ^a, Hyewoo Jeong ^a, Seung Jae Huh ^a, Jinmyoung Joo ^d, Su Ryon Shin^b, Heungsoo Shin ^a,e

^aDepartment of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea

^bDivision of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Cambridge, MA 02139, USA

^cEnvironmental Safety Group, Korea Institute of Science & Technology Europe (KIST-EUROPE), Saarbrücken 66123, Germany

^dDepartment of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea

^eInstitute of Nano Science and Technology, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea

¹These authors contributed equally to this work.

Corresponding author: Heungsoo Shin

Abstract

Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr ²⁺. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr ²⁺ from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr ²⁺. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-12)
연구진국내(교신)+국외 연구진
분야 생명과학 > 생물공학

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