Sarangthem Vijaya, Sharma Harshita, Goel Ridhima, Ghose Sampa, Park Rang-Woon, Mohanty Sujata, Chaudhuri Tapan Kumar, Dinda Amit Kumar, Singh Thoudam Debraj
Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
Stem Cell Facility, DBT Centre of Excellence for Stem Cell Research, All India Institute of Medical Sciences, New Delhi 110029, India.
Int J Biol Macromol. 2022 May 15;207:443-453. doi: 10.1016/j.ijbiomac.2022.03.018. Epub 2022 Mar 8.
Extracellular matrix (ECM) molecules play an important role in regulating molecular signaling associated with proliferation, migration, differentiation, and tissue repair. The identification of new kinds of ECM mimic biomaterials to recapitulate critical functions of biological systems are important for various applications in tissue engineering and regenerative medicine. The use of human elastin derived materials with controlled biological properties and other functionalities to improve their cell-response was proposed. Herein, we reported genetic encoded synthesis of ELP (elastin-like polypeptide) containing ECM domains like RGD (integrin binding ligand) and YIGSR (laminin-selective receptor binding ligand) to regulate cell behaviour in more complex ways, and also better model natural matrices. Thermal responsiveness of the ELPs and structural conformation were determined to confirm its phase transition behaviour. The fusion ELPs derivatives were analysed for mechanical involvement of growth mechanism, regenerative, and healing processes. The designed fusion ELPs promoted fast and strong attachment of fibroblast cells. The fusion ELP derivatives enhanced the migration of keratinocyte cells which of crucial for wound healing. Together it provides a profound matrix for endothelial cells and significantly enhanced tube formation of HUVEC cells. Thus, strategy of using cell adhesive ELP biopolymer emphasizing the role of bioactive ELPs as next generation skin substitutes for regenerative medicine.
细胞外基质（ECM）分子在调节与增殖、迁移、分化和组织修复相关的分子信号传导中发挥着重要作用。识别新型ECM模拟生物材料以重现生物系统的关键功能对于组织工程和再生医学的各种应用至关重要。有人提出使用具有可控生物学特性和其他功能的人弹性蛋白衍生材料来改善其细胞反应。在此，我们报道了含有RGD（整合素结合配体）和YIGSR（层粘连蛋白选择性受体结合配体）等ECM结构域的ELP（弹性蛋白样多肽）的基因编码合成，以更复杂的方式调节细胞行为，并更好地模拟天然基质。测定了ELP的热响应性和结构构象以确认其相变行为。分析了融合ELP衍生物在生长机制、再生和愈合过程中的力学参与情况。设计的融合ELP促进了成纤维细胞的快速和牢固附着。融合ELP衍生物增强了角质形成细胞的迁移，这对伤口愈合至关重要。它共同为内皮细胞提供了一个深厚的基质，并显著增强了人脐静脉内皮细胞（HUVEC）的管形成。因此，使用细胞粘附性ELP生物聚合物的策略强调了生物活性ELP作为再生医学下一代皮肤替代品的作用。
