标题： 通过超分子共组装修复断裂型I型胶原蛋白的α-螺旋肽两亲物从头设计 显示英文标题

标题： De novo design of alpha-helical peptide amphiphiles repairing fragmented collagen type I via supramolecular co-assembly

摘要： 胶原蛋白I型（Col I）的分层三螺旋结构对于细胞外基质的支持和完整性至关重要。然而，当前的重建策略面临链不匹配等挑战，阻碍了正常纤维的形成。在此，我们报告了一种使用全新设计的七氨基酸α-螺旋肽两亲分子（APA）的超分子共组装策略。APA具有疏水的棕榈酸尾部，可稳定螺旋结构并在与互补分子结构相互作用时促进共组装。这种最小设计能够选择性识别片段化胶原蛋白（FC），恢复三螺旋构象并引导纤维形成。我们将这一机制应用于工程化富含FC的纳米脂肪（NF），以制造机械增强的生物材料。将APA-NF与同轴3D打印结合，实现了结构和功能的空间控制。在猪模型中，该平台增强了原位血管化脂肪组织的再生。我们的结果表明，通过肽引导的超分子组装进行胶原蛋白的分层重建为软组织修复提供了一种有前景的策略。 显示英文摘要

摘要： The hierarchical triple-helix structure of collagen type I, Col I, is essential for extracellular matrix support and integrity. However, current reconstruction strategies face challenges such as chain mismatch, preventing proper fibril formation. Here, we report a supramolecular co-assembly strategy using a de novo-designed alpha-helical peptide amphiphile (APA) of just seven amino acids. The APA features a hydrophobic palmitic acid tail, which stabilizes the helical structure and promotes co-assembly upon interaction with complementary molecular structures. This minimal design enables selective recognition of fragmented collagen (FC), restoring triple-helix conformation and guiding fibre formation. We applied this mechanism to engineer FC-rich nanofat (NF) into a mechanically reinforced biomaterial. Integration of APA-NF with coaxial 3D printing enabled spatial control of structure and function. In a porcine model, this platform enhanced in situ vascularized adipose tissue regeneration. Our results demonstrate that hierarchical reconstruction of collagen via peptide-guided supramolecular assembly offers a promising strategy for soft tissue repair.