Double functionalization in chitosan scaffolds for bone tissue engineering improvement

IF 4.6 2区工程技术 Q1 MATERIALS SCIENCE, PAPER & WOOD

Cellulose Pub Date : 2026-08-08 DOI:10.1007/s10570-026-07175-0

Annj Zamuner, Matteo Zoboli, Elena Zeni, Teresa Russo, Ignazio Castagliuolo, Andrea Porzionato, Francesca Ravanetti, Antonio Cacchioli, Gabriella D’Auria, Lucia Falcigno, Chiara Battocchio, Giovanna Iucci, Martina Marsotto, Antonio Gloria, Paola Brun, Monica Dettin

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Abstract

Chitosan is a natural polysaccharide produced by the deacetylation of chitin. It has been employed for several biomedical applications since it is biocompatible and biodegradable. In this work, two synthetic peptides were covalently grafted to chitosan to enhance cellular response. The first sequence, the nonapeptide (351–359) of human vitronectin (HVP), was demonstrated to enhance osteoblast adhesion and migration. The second peptide, GBMP1α, a 22 mer sequence reproducing the fragment (48–69) of BMP-2, increased the osteogenic differentiation of mesenchymal stem cells. The anchoring chemistry involves the formation of a Schiff base between the amino groups of chitosan and aldehyde groups specifically introduced into the peptide backbone, followed by a subsequent reduction step. One of the advantages of this method is the specific anchoring of a bioactive sequence in a single-step reaction carried out in an aqueous solution and mild conditions. Six different 3D-porous scaffolds were designed and obtained by various combinations of both functionalized chitosan and chitosan simultaneously functionalized with both peptides. Scaffolds were characterized through X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and mechanical measurements. Biological assays revealed that functionalized scaffolds exhibited significantly improved adhesion, proliferation, and mineralization in human jaw-derived osteoblasts compared to pristine chitosan. Results from mechanical measurements highlighted the ability to modulate compressive modulus and maximum stress. Notably, scaffolds containing both peptides demonstrated significant synergistic effects in vivo, enhancing material cellular colonization and reducing fibrotic capsule thickness. This study highlights the potential of peptide-functionalized chitosan scaffolds in advancing bone tissue engineering and addressing current limitations in bone repair strategies.

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壳聚糖双功能化支架在骨组织工程中的应用

壳聚糖是由几丁质去乙酰化而成的天然多糖。由于它具有生物相容性和可生物降解性，已被用于几种生物医学应用。本研究将两种合成肽共价接枝到壳聚糖上，以增强细胞反应。第一个序列，人类玻璃体连接蛋白（HVP）的非肽（351-359），被证明能促进成骨细胞的粘附和迁移。第二个肽，GBMP1α，一个22 mer序列复制BMP-2片段（48-69），促进间充质干细胞的成骨分化。锚定化学包括在壳聚糖的氨基和醛基之间形成希夫碱，然后是随后的还原步骤。该方法的优点之一是在水溶液和温和条件下进行的单步反应中特定锚定生物活性序列。通过功能化壳聚糖和两种多肽同时功能化壳聚糖的不同组合，设计并获得了6种不同的3d多孔支架。通过x射线光电子能谱（XPS）、核磁共振（NMR）、傅里叶变换红外光谱（FT-IR）和力学测量对支架进行了表征。生物实验显示，与原始壳聚糖相比，功能化支架在人颌骨来源的成骨细胞中表现出明显改善的粘附、增殖和矿化。机械测量结果强调了调节压缩模量和最大应力的能力。值得注意的是，含有这两种肽的支架在体内表现出显著的协同效应，增强了物质细胞的定植，减少了纤维化囊的厚度。本研究强调了肽功能化壳聚糖支架在推进骨组织工程和解决当前骨修复策略限制方面的潜力。

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来源期刊

Cellulose 工程技术-材料科学：纺织

CiteScore

10.10

自引率

10.50%

发文量

580

审稿时长

3-8 weeks

期刊介绍： Cellulose is an international journal devoted to the dissemination of research and scientific and technological progress in the field of cellulose and related naturally occurring polymers. The journal is concerned with the pure and applied science of cellulose and related materials, and also with the development of relevant new technologies. This includes the chemistry, biochemistry, physics and materials science of cellulose and its sources, including wood and other biomass resources, and their derivatives. Coverage extends to the conversion of these polymers and resources into manufactured goods, such as pulp, paper, textiles, and manufactured as well natural fibers, and to the chemistry of materials used in their processing. Cellulose publishes review articles, research papers, and technical notes.