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

DOI：10.1016/j.bioactmat.2025.10.024

发表期刊：Bioactive Materials

影响因子：20.3

发表时间：2025年11月1日

作者单位：同济大学医学院附属上海肺科医院，同济大学材料科学与工程学院

长段气管缺损修复面临动态力学失配和术后感染两大临床挑战。研究人员创新性地开发了一种血红蛋白交联载药丝素蛋白多孔支架（Hb-SF@LVX），通过双交联策略（血红蛋白催化化学交联与低温诱导物理交联）同步实现动态力学仿生和局部感染控制，实现了气管功能的完整重建。该支架具备优异的弹性模量和疲劳抗力，能模拟天然气管在呼吸、咳嗽中的多向负载响应，同时通过左氧氟沙星的持续释放有效抑制细菌生物膜形成。研究进一步采用模块化组装策略，将预培养的软骨环与支架环交替堆叠构建仿生气管，在兔模型中实现了超过75%的存活率，并促进软骨再生、上皮化和血管化，成功恢复气管结构与功能。

本研究使用由上海攸碧艾生物提供的雌性BALB/c裸鼠进行体内软骨再生实验，将兔耳软骨细胞种植于不同LVX浓度的环状Hb-SF@LVX支架上，并植入裸鼠皮下培养4周和8周。实验结果表明，所有支架组均支持软骨组织形成，再生软骨环呈现典型的软骨结构（Safranin-O和Alcian Blue染色阳性），且随培养时间延长，湿重、厚度、DNA含量、羟基脯氨酸和GAG含量均显著增加（p<0.01），机械性能（轴向、径向和侧向压缩力）接近天然软骨水平，证实该支架在体内环境中能有效促进高质量软骨再生。

Scheme 1. Overall schematic diagram. Anti-infective agent of LVX was mixed into SF solution. Then, in the presence of H2O2, Hb-catalyzed in situ dityrosine chemical crosslinking was induced to react with the SF solution, yielding a “chemically single-crosslinked” Hb-SF@LVX hydrogel. Subsequently, the Hb-SF@LVX hydrogel was further physical crosslinked by introducing of β-sheet crystals via low-temperature freezing, forming a “chemical-physical dual-crosslinked” Hb-SF@LVX scaffold with remarkable elasticity and fatigue resistance. Subsequently, the ring-shaped porous Hb-SF@LVX scaffolds were seeded with chondrocytes derived from rabbit ears and cultured in chondrogenic differentiation medium for 8 weeks to prepare CR. The prepared CR and cell-free ring-shaped Hb-SF@LVX porous scaffolds (serving as SR) were then alternately stacked on a silicone tube to form a “ring-to-tube” structure, to closely mimicking those of the native trachea. The prepared constructs were then transplanted into the para-muscular pouch of autologous rabbits. After 3 weeks of in vivo implantation, BT with retained vascular pedicles were generated and subsequently used for in situ tracheal transplantation, leveraging dynamic mechanical biomimicry and infection control to facilitate LSTD reconstruction.