권재원 (KIST)

한빛사논문

조회257

권재원Jae Won Kwon

KIST

Adv. Sci., Mar 12 2024, | https://doi.org/10.1002/advs.202305852 Human Fibroblast-Derived Matrix Hydrogel Accelerates Regenerative Wound Remodeling Through the Interactions with Macrophages

Cininta Savitri ^{1 †}, Sang Su Ha ^{1 †}, Jae Won Kwon ^{1 2 †}, Sung Hoon Kim ¹, Young-Min Kim ^{1 2}, Hyun Mee Park ³, Haejin Kwon ³, Mi Jung Ji ³, Kwideok Park ^{1 2 *}

¹Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
²Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul, 02792, Republic of Korea.
³Advanced Analysis and Data Center, KIST, Seoul, 02792, Republic of Korea.

^†C.S., S.S.H., and J.W.K. contributed equally to this work.
^*Corresponding author: correspondence to Kwideok Park

Abstract

Herein, a novel extracellular matrix (ECM) hydrogel is proposed fabricated solely from decellularized, human fibroblast-derived matrix (FDM) toward advanced wound healing. This FDM-gel is physically very stable and viscoelastic, while preserving the natural ECM diversity and various bioactive factors. Subcutaneously transplanted FDM-gel provided a permissive environment for innate immune cells infiltration. Compared to collagen hydrogel, excellent wound healing indications of FDM-gel treated in the full-thickness wounds are noticed, particularly hair follicle formation via highly upregulated β-catenin. Sequential analysis of the regenerated wound tissues disclosed that FDM-gel significantly alleviated pro-inflammatory cytokine and promoted M2-like macrophages, along with significantly elevated vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) level. A mechanistic study demonstrated that macrophages-FDM interactions through cell surface integrins α5β1 and α1β1 resulted in significant production of VEGF and bFGF, increased Akt phosphorylation, and upregulated matrix metalloproteinase-9 activity. Interestingly, blocking such interactions using specific inhibitors (ATN161 for α5β1 and obtustatin for α1β1) negatively affected those pro-healing growth factors secretion. Macrophages depletion animal model significantly attenuated the healing effect of FDM-gel. This study demonstrates that the FDM-gel is an excellent immunomodulatory material that is permissive for host cells infiltration, resorbable with time, and interactive with macrophages, where it thus enables regenerative matrix remodeling toward a complete wound healing.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-14)
연구진국내 연구진
분야 바이오·의료융합 > 바이오소재

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