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矿化几丁质纳米晶体增强壳聚糖三维多孔生物杂交支架促进骨组织再生的骨诱导能力。

Mineralized chitin nanocrystals enhance osteoinductive ability of chitosan 3D porous biohybrid scaffolds for bone tissue regeneration.

作者信息

Olza Sheila, Hadj Bouzidi Nabil M, Rubatat Laurent, Pellerin Virginie, Montejo Unai, Alonso-Varona Ana, Fernandes Susana C M

机构信息

Universite de Pau et des Pays de l' Adour, IPREM, E2S UPPA, CNRS, 64 000 Pau, France; Department of Cellular Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), B Sarriena, s/n, 48940 Leioa, Spain.

Universite de Pau et des Pays de l' Adour, IPREM, E2S UPPA, CNRS, 64 000 Pau, France.

出版信息

Carbohydr Polym. 2025 Oct 15;366:123911. doi: 10.1016/j.carbpol.2025.123911. Epub 2025 Jun 17.

DOI:10.1016/j.carbpol.2025.123911
PMID:40733832
Abstract

The loss of alveolar bone due to periodontitis has high worldwide prevalence, and Tissue Engineering (TE) emerges as an alternative to replace autologous bone grafting. Herein, TE fundamentals were applied to mimic bone extracellular matrix (ECM) and cells microenvironment. First, biomimetic hydroxyapatite-based mineralized chitin nanocrystals (MCHNC) from both alpha or beta isoforms were synthesized, showing excellent in vitro biocompatibility and osteoinductive properties over human adipose-derived mesenchymal stem cells (hASCs) osteogenic differentiation. Then, biohybrid 3D porous biomaterials were obtained by combining MCHNC as inorganic nanoparticles, chitosan (CS) as organic matrix and hASCs spheroids. The biohybrids showed an improvement of the mechanical properties over non-mineralized scaffolds. Furthermore, they presented high in vitro biocompatibility and bioactivity, providing an adequate microenvironment for cells. In particular, CS/MβCHNC biomaterial presented the greatest mechanical properties (191 ± 10 kPa). Additionally, the incorporation of MβCHNC provided the biomaterial with osteoinductive character, since hASCs showed increased ALP activity (3.5-fold) and higher matrix mineralization (26.3-fold), even when cultured in standard cell culture medium. Finally, the osteospheroids showed very good integration into the CS/MβCHNC biomaterial, with great migration and colonization of viable cells. These findings demonstrate the potential of CS/MβCHNC biomaterial for TE as alveolar bone regeneration.

摘要

由于牙周炎导致的牙槽骨丧失在全球范围内具有很高的患病率,组织工程(TE)作为替代自体骨移植的一种方法应运而生。在此,应用组织工程基本原理来模拟骨细胞外基质(ECM)和细胞微环境。首先,合成了来自α或β亚型的仿生羟基磷灰石基矿化几丁质纳米晶体(MCHNC),在人脂肪来源间充质干细胞(hASCs)成骨分化方面显示出优异的体外生物相容性和骨诱导特性。然后,通过将MCHNC作为无机纳米颗粒、壳聚糖(CS)作为有机基质与hASCs球体相结合,获得了生物杂交三维多孔生物材料。与非矿化支架相比,这种生物杂交材料的力学性能有所改善。此外,它们具有高体外生物相容性和生物活性,为细胞提供了适宜的微环境。特别是,CS/MβCHNC生物材料表现出最大的力学性能(191±10 kPa)。此外,MβCHNC的加入赋予了生物材料骨诱导特性,因为即使在标准细胞培养基中培养,hASCs的碱性磷酸酶(ALP)活性也增加了(3.5倍),基质矿化程度更高(26.3倍)。最后,成骨球体显示出很好地整合到CS/MβCHNC生物材料中,有大量活细胞迁移和定植。这些发现证明了CS/MβCHNC生物材料在组织工程中用于牙槽骨再生的潜力。

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