한빛사논문
- 조회516
Fatemeh Zehtabi1, Ankit Gangrade1, Kaylee Tseng1,2, Reihaneh Haghniaz1, Reza Abbasgholizadeh1, Hossein Montazerian1,3,4, Danial Khorsandi1, Jamal Bahari1, Amir Ahari1, Neda Mohaghegh1, Negar Hosseinzadeh Kouchehbaghi1,5, Kalpana Mandal1, Marvin Mecwan1, Ahmad Rashad1, Natan Roberto de Barros1, Youngjoo Byun6, Menekse Ermis,1* Han-Jun Kim,1,7,8* and Ali Khademhosseini1*
1Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90064 USA
2Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, 90007 USA
3Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095 USA
4California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, 90095 USA
5Department of Textile Engineering, Amirkabir University of Technology (Tehran Polytechnic), Hafez Avenue, Tehran, 1591634311 Iran
6College of Pharmacy, Korea University, Sejong, 30019 Republic of Korea
7College of Pharmacy, Korea University, Sejong, 30019 Republic of Korea
8Vellore Institute of Technology (VIT), Vellore, 632014 India
CORRESPONDING AUTHORS : Menekse Ermis, Han-Jun Kim, Ali Khademhosseini
Abstract
Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)-mediated aneurysm progression. This study incorporates doxycycline (DOX), a well-known sclerosant and MMPs inhibitor, into a shear-thinning biomaterial (STB)-based vascular embolizing hydrogel. The addition of DOX is expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results show that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX are injectable and have a twofold increase in storage modulus compared to those without DOX. STB-DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels show sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells shows MMP inhibition (approximately an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occlude a patient-derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB-DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels.
논문정보
- Research article
- 2023년 09월 (BRIC 등록일 2023-12-06)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오소재
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