Hemoglobin-crosslinked drug-loaded silk fibroin porous scaffold for long-segment tracheal defect repair: An integrated strategy leveraging dynamic mechanical biomimicry and infection control

The clinical repair of long-segment tracheal defects (LSTDs) remains a formidable challenge, primarily due to the dynamic mechanical mismatch of current implantable substitutes and high rates of postoperative infection. To address these critical hurdles, we have engineered a novel silk fibroin (SF)-based scaffold, designated Hb-SF@LVX, that simultaneously achieves dynamic mechanical biomimicry and robust infection control. By employing a synergistic dual-crosslinking strategy—combining hemoglobin (Hb)-catalyzed chemical crosslinking with low-temperature-induced β-sheet formation—the scaffold exhibits remarkable elasticity and fatigue resistance, closely mimicking the properties of native tracheal tissue. Furthermore, the scaffold was efficiently loaded with levofloxacin (LVX) and demonstrated prolonged, sustained release, conferring potent antibacterial andanti-biofilm efficacy. To replicate the intricate hierarchical architecture of the native trachea, we modularly assembled pre-cultured cartilage rings (CRs) with optimized scaffold rings (SRs), fabricating a biomimetic trachea (BT) with a “CRs-SRs” structure.In situtransplantation in a rabbit LSTD model revealed that the SF-120 BT, carrying an optimal LVX concentration, achieved a survival rate exceeding 75 %. Compared to the control group, it demonstrated substantially improved luminal patency and mechanical performance. Crucially, it successfully suppressed infection, mitigated inflammation, and promoted high-quality regeneration of cartilage, fibrous connective tissue, as well as facilitating epithelialization and vascularization. These comprehensive outcomes culminated in the successful structural and functional reconstruction of the defective trachea. Collectively, this research establishes a new paradigm for the clinical management of LSTDs by integrating adaptable dynamic mechanics, effective infection control, and enhanced tissue regeneration within a single, innovative platform.Image 1View The PDF

长段气管缺损（long-segment tracheal defects, LSTDs）的临床修复仍是一项极具挑战性的难题，其核心瓶颈在于当前可植入替代物存在动态力学匹配性不足的问题，且术后感染发生率居高不下。为攻克这一关键临床难题，我们研发了一种新型丝素蛋白（silk fibroin, SF）基支架，命名为Hb-SF@LVX，该支架可同时实现动态力学仿生性能与高效感染防控能力。通过协同双交联策略——将血红蛋白（hemoglobin, Hb）催化的化学交联与低温诱导的β-折叠形成相结合，该支架展现出优异的弹性与抗疲劳性能，可高度模拟天然气管组织的力学特性。此外，该支架可高效负载左氧氟沙星（levofloxacin, LVX），并展现出持久的缓释性能，从而具备强效的抗菌与抗生物膜活性。为复现天然气管复杂的层级结构，我们将预培养的软骨环（cartilage rings, CRs）与优化后的支架环（scaffold rings, SRs）进行模块化组装，制备出具有"CRs-SRs"结构的仿生气管（biomimetic trachea, BT）。在兔LSTD模型中开展原位移植实验的结果显示，搭载最优浓度LVX的SF-120 BT存活率超过75%。与对照组相比，其管腔通畅性与力学性能均得到显著改善。尤为关键的是，该支架可有效抑制感染、减轻炎症反应，并促进软骨、纤维结缔组织的高质量再生，同时加速上皮化与血管化进程。上述一系列综合效果最终实现了缺损气管的结构与功能重建。综上，本研究通过在单一创新平台中整合可适配的动态力学性能、高效感染防控能力与强化的组织再生效果，为LSTDs的临床治疗建立了全新的范式。含图1及对应PDF文档。