Peled Eli, Boss Jochanan, Bejar Jacob, Zinman Chaim, Seliktar Dror
Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
J Biomed Mater Res A. 2007 Mar 15;80(4):874-84. doi: 10.1002/jbm.a.30928.
The aim of this study is to investigate regeneration in a segmental bone defect using a novel fibrinogen-based hydrogel material. The use of hydrogels made from poly(ethylene glycol) (PEG) conjugated to fibrinogen for this purpose may be better to conventional fibrin-based materials as it offers an additional degree of control over the structural characteristics and biodegradation of the material. At the same time, it maintains some of the inherent biofunctionality of the fibrinogen molecule. PEGylated fibrinogen hydrogels with various degrees of proteolytic resistance based on PEG and fibrinogen composition were designed for slow, intermediate, and fast biodegradation. The hydrogels were implanted into 7-mm segmental rat tibial defects without additional osteoinductive factors with the rationale that the ingrowth matrix will displace the normal fibrin clot while sustaining a similar healing effect for a longer duration. Histological and X-ray results confirmed that the extent and distribution of newly formed bone in the defect after 5 weeks strongly parallels the biodegradation pattern of the implanted material. When compared to nonunions in animals treated with the fast-degrading implants and untreated control animals, the rats implanted with the intermediate-degrading material exhibited osteoneogenesis. This data supports the hypothesis that the perseverance of the PEGylated fibrinogen material can be synchronized with the optimal healing characteristics of a segmental osseous defect and that the consequent sustained release of fibrinogen fragments facilitates the osteogenic response at the injury site. The PEGylated fibrinogen material may, therefore, be a highly efficacious material for promoting the healing of bone defects and especially nonunion fractures.
本研究的目的是使用一种新型的基于纤维蛋白原的水凝胶材料来研究节段性骨缺损的再生情况。为此，将聚乙二醇（PEG）与纤维蛋白原共轭制成的水凝胶可能比传统的纤维蛋白基材料更好，因为它能对材料的结构特征和生物降解提供额外的控制程度。同时，它保留了纤维蛋白原分子的一些固有生物功能。基于PEG和纤维蛋白原的组成，设计了具有不同程度抗蛋白水解能力的聚乙二醇化纤维蛋白原水凝胶，用于缓慢、中等和快速生物降解。将这些水凝胶植入7毫米的大鼠胫骨节段性缺损中，不添加额外的骨诱导因子，其原理是向内生长的基质将取代正常的纤维蛋白凝块，同时在更长的时间内维持类似的愈合效果。组织学和X射线结果证实，5周后缺损处新形成骨的范围和分布与植入材料的生物降解模式密切平行。与用快速降解植入物治疗的动物和未治疗的对照动物中的骨不连相比，植入中等降解材料的大鼠表现出骨生成。这些数据支持这样的假设，即聚乙二醇化纤维蛋白原材料的持久性可以与节段性骨缺损的最佳愈合特征同步，并且随之而来的纤维蛋白原片段的持续释放促进了损伤部位的成骨反应。因此，聚乙二醇化纤维蛋白原材料可能是促进骨缺损尤其是骨不连骨折愈合的一种高效材料。
