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Acta Biomater., 2023 Feb;157:137-148 | https://doi.org/10.1016/j.actbio.2022.11.050 3D printed multi-growth factor delivery patches fabricated using dual-crosslinked decellularized extracellular matrix-based hybrid inks to promote cerebral angiogenesis

Seung Hyeon Hwang ^a,1, Jongbeom Kim ^b,1, Chaejeong Heo ^c, Jungbin Yoon ^a, Hyeonji Kim ^a, Se-Hwan Lee ^b, Hyung Woo Park ^d,e, Man Seung Heo^d,e, Hyo Eun Moon ^d,e, Chulhong Kim^a,b,f,g,h, Sun Ha Paek ^d,e, Jinah Jang ^a,b,g,h

^aDepartment of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang 37673, Republic of Korea
^bDepartment of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang 37673, Republic of Korea
^cCenter for Integrated Nanostructure Physics (CINAP), Institute for Basic Science (IBS), Suwon 16419, Republic of Korea
^dDepartment of Neurosurgery, Cancer Research Institute, Ischemia/Hypoxia Disease Institute, Seoul National University, College of Medicine, Seoul 03080, Republic of Korea
^eAdvanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea
^fDepartments of Electrical Engineering, and Medical Device Innovation Center, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 37673, Republic of Korea
^gSchool of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang 37673, Republic of Korea
^hInstitute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea

¹These authors contributed equally to this work.
Corresponding authors : Chulhong Kim, Sun Ha Paek, Jinah Jang

Abstract

Generally, brain angiogenesis is a tightly regulated process, which scarcely occurred in the absence of specific pathological conditions. Delivery of exogenous angiogenic factors enables the induction of desired angiogenesis by stimulating neovasculature formation. However, effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. Herein, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs), using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink for printing patches through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition reaction with combining methacrylated hyaluronic acid (HAMA) and vascular-tissue-derived decellularized extracellular matrix (VdECM), and thermal crosslinking of VdECM. 3D printing technology, a useful approach with fabrication versatility with customizable systems and multiple biomaterials, is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by label-free photoacoustic microscopy in vivo. The developed multi-GFs releasing patch may offer a promising therapeutic approach of spatiotemporal drugs releasing such as cerebral ischemia, ischemic heart diseases, diabetes, and even use as vaccines. STATEMENT OF SIGNIFICANCE: Effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. In this study, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs) using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition, and thermal crosslinking. 3D printing technology is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by photoacoustic microscopy in vivo.

논문정보

형식Research article
게재일2023년 02월 (BRIC 등록일 2023-02-14)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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