Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering
Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering
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DOI：
10.1016/j.biomaterials.2012.06.075
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发表时间：
2012-10-01
期刊：
影响因子：
14
通讯作者：
Iseki, Sachiko
中科院分区：
文献类型：
--
作者：
Fujioka-Kobayashi, Masako;Ota, Masato S.;Iseki, Sachiko
为了创建允许蛋白质（如生长因子）在长期内受控释放的药物递送系统，通过与含硫醇的聚乙二醇交联，使含胆固醇基和丙烯酰基的普鲁兰（CHPOA）纳米凝胶聚集以形成快速降解的水凝胶（CHPOA/水凝胶）。使用生理活性材料进行临床骨重建治疗的金标准是使用重组人骨形态发生蛋白2（BMP 2）进行治疗;然而，这种方法具有局限性，例如炎症、成本效益差和个体间易感性不同。在这项研究中，两种不同的生长因子，BMP 2和重组人成纤维细胞生长因子18（FGF 18），施加到一个临界大小的颅骨骨缺损的骨修复的CHPOA/水凝胶系统。CHPOA-FGF 18/水凝胶显示出与对照CHPOA-PBS/水凝胶相同的结果，并且CHPOA-BMP 2/水凝胶处理不完全诱导骨修复。相比之下，CHPOA-FGF 18 + BMP 2/水凝胶处理强烈增强和稳定BMP 2依赖性骨修复，诱导水凝胶内部和周围的骨祖细胞浸润。该报告表明，CHPOA/水凝胶系统可以成功地将两种不同的蛋白质递送到骨缺损处，以诱导有效的骨修复。CHPOA/水凝胶系统与生长因子FGF 18和BMP 2的组合可能是迈向高效骨组织工程的一步。(C)2012爱思唯尔有限公司版权所有。
To create a drug delivery system that allows the controlled release of proteins, such as growth factors, over a long-term period, cholesteryl group- and acryloyl group-bearing pullulan (CHPOA) nanogels were aggregated to form fast-degradable hydrogels (CHPOA/hydrogels) by cross-linking with thiol-bearing polyethylene glycol. The gold standard of clinical bone reconstruction therapy with a physiologically active material is treatment with recombinant human bone morphogenetic protein 2 (BMP2); however, this approach has limitations, such as inflammation, poor cost-efficiency, and varying interindividual susceptibility. In this study, two distinct growth factors, BMP2 and recombinant human fibroblast growth factor 18 (FGF18), were applied to a critical-size skull bone defect for bone repair by the CHPOA/hydrogel system. The CHPOA-FGF18/hydrogel displayed identical results to the control CHPOA-PBS/hydrogel, and the CHPOA-BMP2/hydrogel treatment imperfectly induced bone repair. By contrast, the CHPOA-FGF18 + BMP2/hydrogel treatment strongly enhanced and stabilized the BMP2-dependent bone repair, inducing osteoprogenitor cell infiltration inside and around the hydrogel. This report indicates that the CHPOA/hydrogel system can successfully deliver two different proteins to the bone defect to induce effective bone repair. The combination of the CHPOA/hydrogel system with the growth factors FGF18 and BMP2 might be a step towards efficient bone tissue engineering. (C) 2012 Elsevier Ltd. All rights reserved.