有望な骨補填材の骨再生力を増強―リン酸八カルシウム/ゼラチン/コラーゲン様ペプチド組成が骨形成を促進―

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2026-03-27 東北大学

東北大学の研究チームは、骨補填材であるリン酸八カルシウム/ゼラチン複合体(OCP/Gel)にコラーゲン様ペプチド(CMP)を加えることで、骨再生能力を大幅に向上させることを明らかにした。CMPの導入により、骨芽細胞による骨基質の石灰化が促進され、材料全体の骨形成能が増強されることが確認された。さらに、その細胞・分子レベルの作用メカニズムも提案された。本成果は、自家骨に近い高い再生能力を持つ次世代骨補填材の開発につながり、整形外科や歯科領域での臨床応用の拡大が期待される。

有望な骨補填材の骨再生力を増強―リン酸八カルシウム/ゼラチン/コラーゲン様ペプチド組成が骨形成を促進―
図1. OCP/Gel/CMPが骨再生を促進する要約図。

<関連情報>

コラーゲン模倣ペプチドをリン酸八カルシウム/ゼラチン複合体に添加すると、石灰化が促進され骨形成が強化される Addition of a collagen mimetic peptide to octacalcium phosphate/gelatin composites enhances bone formation by accelerating calcification

Kento Harada, Ryo Hamai, Yu Mori, Tomoka Hasegawa, Ryuichi Kanabuchi, Kaori Tsuchiya, Norio Amizuka, Toshimi Aizawa, Osamu Suzuki
Acta Biomaterialia  Available onlin: 25 March 2026
DOI:https://doi.org/10.1016/j.actbio.2026.03.043

Abstract

Octacalcium phosphate/gelatin (OCP/Gel) composites exhibit osteogenicity primarily due to OCP bioactivity; however, further improvement of their capacity is necessary for various bone defects. This study was conducted to investigate whether the addition of a collagen-mimetic peptide (CMP; (Gly-Pro-Hyp)10), which forms a triple helix at physiological temperature, further enhances the osteogenic potential of OCP/Gel. Following the synthesis of OCP, spongy Gel and 44 wt% OCP-containing Gel were prepared from 3 w/v% gelatin solution with or without 0.1 w/v% CMP: 3%Gel, 3%Gel/CMP, OCP/3%Gel, and OCP/3%Gel/CMP. The materials were characterized physicochemically and evaluated in vitro and in vivo. Raman spectroscopy confirmed that the CMP-triple helix was maintained in OCP/Gel sponges. 3D hybrid spheroid culture of mesenchymal stromal cells (MSCs) with the materials showed that OCP/3%Gel/CMP and OCP/3%Gel increased alkaline phosphatase activities by day 7 compared to OCP alone. CMP inclusion in OCP/3%Gel altered gene expression for cytoskeletal organization and immunomodulation in MSCs, as assessed by transcriptomic and PCR analyses of extracted mRNA. Histomorphometry and transmission electron microscopy using non-decalcified sections revealed that the calcified matrix formation area was maximized in OCP/3%Gel/CMP (40.0%), followed by OCP/3%Gel (32.7%) and OCP (21.9%), and that osteoblasts were closely associated with crystal formation within the calcified deposits nucleated in the 3%Gel/CMP matrix during OCP hydrolysis. OCP/3%Gel/CMP enhanced both osteoblasts and osteoclasts accumulation and bone formation more than OCP/3%Gel at 4 weeks after implantation in the rat transcortical femoral defects. The results suggest that CMP-triple helix inclusion may induce Gel substrate calcification, thereby enhancing osteogenesis by the OCP/Gel composite.

Statement of significance

A composite of octacalcium phosphate and gelatin (OCP/Gel) was the focus of this study highlighting the effects of a collagen mimetic peptide (CMP, (Gly-Pro-Hyp)10) addition. Gelatin adopts a random-coil structure at physiological temperatures but forms a triple-helix-like structure during cooling gelation of OCP/Gel preparation. Although this structure may be preserved through dehydrothermal cross-linking, it remains less robust than that of native collagen. Using a CMP maintaining a triple-helix structure at physiological temperatures, how this CMP addition affects the gelatin biocompatibility and enhances the osteogenecity of OCP/Gel was studied. Unexpectedly, adding this specific CMP to OCP/Gel promoted not only gelatin matrix calcification but also provided a nucleation site for osteoblastic mineralization in Gel, thereby accelerating overall bone formation by OCP/Gel.

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