Biomimetic glycopeptide hydrogel coated PCL/nHA scaffold for enhanced cranial bone regeneration via macrophage M2 polarization-induced osteo-immunomodulation

The reconstruction of large cranial bone defects by bioactive materials without exogenous cells or growth factors remains a substantial clinical challenge. Here, synthetic fibrous glycopeptide hydrogel (GRgel) self-assembled by β-sheet RADA16-grafted glucomannan was designed to mimic the glycoprotei...

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Veröffentlicht in:Biomaterials 2022-06, Vol.285, p.121538-121538, Article 121538
Hauptverfasser: Wang, Yaping, Wang, Jingrong, Gao, Rui, Liu, Xiang, Feng, Zujian, Zhang, Chuangnian, Huang, Pingsheng, Dong, Anjie, Kong, Deling, Wang, Weiwei
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Sprache:eng
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Zusammenfassung:The reconstruction of large cranial bone defects by bioactive materials without exogenous cells or growth factors remains a substantial clinical challenge. Here, synthetic fibrous glycopeptide hydrogel (GRgel) self-assembled by β-sheet RADA16-grafted glucomannan was designed to mimic the glycoprotein composition and the fibrillar architecture of natural extracellular matrix (ECM), which was non-covalently composited with 3D-printed polycaprolactone/nano hydroxyapatite (PCL/nHA) scaffold for cranial bone regeneration. The glycopeptide hydrogel significantly promoted the proliferation, osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by GRgel-induced macrophage M2-phonotype polarization and the effective M2 macrophage-BMSC crosstalk. The repair of critical-size skull bone defect in rat indicated a superior efficacy of PCL/nHA@GRgel implant on bone regeneration and osseointegration, with an average bone area of 83.3% throughout the defect location at 12 weeks post treatment. Furthermore, the osteo-immunomodulatory GRgel induced a reparative microenvironment similar with that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and osteoblasts, and high-level vascularization. Collectively, the composite scaffold developed here with macrophage polarization-mediated osteo-immunomodulation may represent a promising implant for expediting in situ bone regeneration by providing biochemical and osteoinductive cues at the injured tissue.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2022.121538