| 研究課題/領域番号 |
21F21353
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| 配分区分 | 補助金 |
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| 研究機関 | 九州大学 |
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研究代表者 |
井嶋 博之 九州大学, 工学研究院, 教授 (10274515)
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| 研究分担者 |
SHAFIQ MUHAMMAD 九州大学, 工学(系)研究科(研究院), 外国人特別研究員
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| 研究期間 (年度) |
2021-11-18 – 2024-03-31
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| キーワード | Hybrid vascular graft / Decellularized ECM / Polycaprolactone / Nanofibrous Membrane / Tubular scaffold / Electrospun membrane |
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| 研究実績の概要 |
The objective of this research is to foster instructive biomaterials to promote in situ tissue repair. Soluble and tethered biological cues as well as extracellular matrix (ECM)-mimicking scaffolds hold great promise. Growth factors (GFs) as well as cytokines and chemokines play a pivotal role for tissue repair, however, they can be easily degraded in vitro and in vivo owing to their short half-life and poor stability. Short amino-acid sequences, which can fully recapitulate the bioactivity of full-length proteins while ensuring an easy manufacturing and good stability offer an alternative paradigm. Therefore, the overarching goal of research in this fiscal year was to fabricate ECM-mimicking scaffolds and to modify them with GFs and other bioactive cues for a functional tissue repair.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Vascular endothelial growth factor (VEGF) is a potent angiogenic cue, while stromal cell-derived factor-1 alpha (SDF-1α) is a stem cell inducing/recruiting factor. The levels of VEGF and SDF-1α transiently increase following tissue injury, however sharply decline owing to matrix metalloproteinases. We conjugated VEGF-recruiting prominin-1-derived peptide (PR1P) and SDF-1α peptide with polycaprolactone (PCL, Mw = 14 kDa) and blended them along with PCL (Mw = 80 kDa) to fabricate vascular grafts. In vivo evaluation in an abdominal aorta revealed marked effect of dual cues for endogenous cell mobilization/recruitment and in situ blood vessel regeneration. We also fabricated heparin-immobilized electrospun fibers; as well as decellularized extracellular matrix (dECM)-based core/shell fibers for GFs immobilization.
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| 今後の研究の推進方策 |
The above findings indicated beneficial effect of GFs and bioactive cues. ECM confers instructive cues to tissues and organs, thanks to its composition and localization as well as its ability to harbor soluble and tethered ligands. Our preliminary studies have indicated beneficial effect of heparinization for GFs immobilization. ECM is also composed of glycosaminoglycans, which may also bind endogenous and exogenous biological cues. We have prepared dECM from different tissues, such as nerves and aorta and successfully fabricated core/shell fibers; the core was composed of PCL/gelatin, while the shell was comprised of dECM. A battery of in vitro and in vivo tests will be performed to reveal the potential of dECM-based fibers to promote GFs immobilization as well as tissue repair in vitro and in vivo.
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