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조회405

전남대학교병원

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Bioact. Mater., 2023 Aug 29;31:395-407 | https://doi.org/10.1016/j.bioactmat.2023.08.020 A paintable and adhesive hydrogel cardiac patch with sustained release of ANGPTL4 for infarcted heart repair.

Mingyu Lee ^a,1, Yong Sook Kim ^b,c,1, Junggeon Park ^a, Goeun Choe ^a, Sanghun Lee ^a, Bo Gyeong Kang ^b, Ju Hee Jun ^b, Yoonmin Shin ^d, Minchul Kim ^d,e, Youngkeun Ahn ^b,d,e, Jae Young Lee^a

^aSchool of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea

^bCell Regeneration Research Center, Chonnam National University, Gwangju, Republic of Korea

cBiomedical Research Institute, Chonnam National University Hospital, Gwangju, Republic of Korea

^dDepartment of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea

^eChonnam National University Medical School, Gwangju, Republic of Korea

¹These authors contributed equally to this work.

Corresponding authors: Youngkeun Ahn, Jae Young Lee

Abstract

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-10-06)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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