2023 Fiscal Year Final Research Report
Starburst hemoglobin polymer with controlled physical properties as a red blood cell substitute
| Project/Area Number |
21K12688
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
酒井 宏水 奈良県立医科大学, 医学部, 教授 (70318830)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 人工臓器学 / 赤血球代替物 / 高分子科学 / 超分子化学 / ヘモグロビン / 解離平衡 / 架橋 |
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| Outline of Final Research Achievements |
Various chemical modifications of hemoglobin (Hb) have been investigated to produce artificial oxygen carriers. At the beginning of this research, we aimed to construct a starburst polymer with a regularly arranged Hb-PEG structure. We synthesized monocyclic Hb monomers and a bicyclic Hb dimer for use as arms and a core of starburst polymer. Thermodynamic analysis of ring-opening polymerization of cyclic monomers clearly showed an entropy-driven mechanism: a cyclic Hb monomer with a larger ring size preferred to form a supramolecular Hb polymer.
A supramolecular polymer gel was obtained by ring-opening polymerization of bicyclic Hb dimer. The gel has a unique network structure cross-linked by non-covalent interactions between Hb subunits. Therefore, research shifted to evaluating its physical properties and controlling its viscoelasticity. The rheology of the obtained gel changed significantly in response to changes in pH and additives that affect the interactions between Hb subunits.
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| Free Research Field |
生体医工学・生体材料学
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| Academic Significance and Societal Importance of the Research Achievements |
Hbを重合して人工酸素運搬体を作製する試みが欧米を中心に進められているが、ランダム重合Hbは重合度が小さく、低分子量の成分が副作用の原因となる。環状構造を持つ修飾Hbを単量体とみなし、開環重合して得られるHbポリマーは、決まった構造のリンカーによりHb同士が連結されているため、Hbを規則的に配置できるなど従来法に比べ多くの長所を有する。本研究ではこの手法を用いてHbを高効率に重合し、Hbのサブユニット間相互作用を介した三次元網目構造を持つ超分子ポリマーゲルを合成した。この成果は網目構造以外の固有の三次元構造の構築にも応用可能であり、既存のランダム重合法の課題を解決する糸口になると期待される。
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