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肝素/达肝素对丝素蛋白结构及皮肤伤口愈合物理性能的改性效果评估

Evaluation of the Modification Effects of Heparin/Dalteparin on Silk Fibroin Structure and Physical Properties for Skin Wound Healing.

作者信息

Hama Rikako, Nakazawa Yasumoto

机构信息

Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-Cho, Koganei 184-8588, Japan.

出版信息

Polymers (Basel). 2024 Jan 24;16(3):321. doi: 10.3390/polym16030321.

Abstract

We have developed a functionalized silk fibroin (BSF) that can serve as an improved fundamental material for dressings by specifically capturing growth factors secreted during the healing process and supplying them to cells accumulated in the wound area to enhance the tissue regeneration efficiency. When considering the design of heparin-modified BSF, there is a difficulty with binding to high-molecular-weight polysaccharides without disrupting the hydrophobic crystalline structure of the BSF. In this study, a low-molecular-weight pharmaceutical heparin, dalteparin, was selected and cross-linked with the tyrosine residue presence in the BSF non-crystalline region. When targeting 3D porous applications like nanofiber sheets, as it is crucial not only to enhance biological activity but also to improve handling by maintaining stability in water and mechanical strength, a trade-off between improved cell affinity and reduced mechanical strength depending on crystalline structure was evaluated. The use of dalteparin maintained the mechanical strength better than unfractionated heparin by reducing the effect on disturbing BSF recrystallization. Film surface hydrophilicity and cell proliferation induction were significantly higher in the dalteparin group. For BSF functionalization, using purified heparin was an effective approach that achieved a balance between preserving the mechanical properties and induction of tissue regeneration, offering the potential for various forms in the future.

摘要

我们开发了一种功能化丝素蛋白(BSF),它可以作为一种改良的敷料基础材料,通过特异性捕获愈合过程中分泌的生长因子,并将其提供给伤口区域聚集的细胞,从而提高组织再生效率。在考虑肝素修饰的BSF设计时,存在一个难题,即如何在不破坏BSF疏水晶体结构的情况下与高分子量多糖结合。在本研究中,选择了低分子量药用肝素达肝素,并使其与BSF非晶区中存在的酪氨酸残基交联。当针对纳米纤维片等3D多孔应用时,不仅提高生物活性很关键,而且通过保持在水中的稳定性和机械强度来改善操作性也很重要,因此评估了根据晶体结构在提高细胞亲和力和降低机械强度之间的权衡。达肝素的使用通过减少对BSF重结晶的干扰作用,比未分级肝素更好地保持了机械强度。达肝素组的膜表面亲水性和细胞增殖诱导明显更高。对于BSF功能化,使用纯化肝素是一种有效的方法,在保持机械性能和诱导组织再生之间实现了平衡,为未来的各种形式提供了潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad60/10857336/09fa4cc91e27/polymers-16-00321-g001.jpg

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