Zheng Siqiang, Xu Li, Bo Qitao, Gao Erji, Zheng Enkuo, Xie Lei, Zhao Bin, Yi Jiaoyu, Li Yang, Xu Yong, Wang Yao, Tao Bo
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
The Second Hospital of Ningbo, Ningbo, 315010, China.
Mater Today Bio. 2025 May 8;32:101831. doi: 10.1016/j.mtbio.2025.101831. eCollection 2025 Jun.
Restoring tracheal defects remains a significant challenge in tissue engineering and regenerative medicine. Current scaffolds fall short of achieving optimal tracheal repair due to unmatched mechanical properties and limited anti-inflammatory properties. In this study, we incorporated the natural plant-derived anti-inflammatory molecule Xanthohumol (XN) into the backbone of a degradable polyurethane (PEUU) to create a porous PEXUU scaffold with tailorable mechanical properties and sustained anti-inflammatory activity. Materials Studio software was initially employed to simulate the feasibility of synthesizing the PEXUU elastomer using XN as a chain extender and poly(ε-caprolactone) as the soft segment. Mechanical tests confirmed the synthesized PEXUU elastomer exhibited excellent elasticity and fatigue resistance that closely mimic the mechanical properties of the natural trachea. The PEXUU elastomers were then processed into porous scaffolds via thermally induced phase separation, exhibited high porosity and favorable hydrophilicity while providing durable XN release kinetic in a sustained manner during degradation. co-culture studies demonstrated that the scaffold not only exhibited favorable biocompatibility and supported cartilage regeneration but also effectively downregulated pro-inflammatory factor expression and promoted the polarization of M1 macrophages toward the M2 phenotype. Furthermore, experiments revealed that implantation of the PEXUU scaffold significantly alleviated local inflammation and facilitated the formation of mature cartilage tissue. In a rabbit tracheal window defect model, the scaffold markedly reduced granulation tissue formation and preserved luminal patency, ultimately yielding excellent repair outcomes. In conclusion, XN bulk-modified PEUU represents a dual-function strategy that combines tailorable mechanical compliance with sustained anti-inflammatory activity. This approach significantly promotes tracheal regeneration and repair, offering promising prospects for clinical application.
在组织工程和再生医学中，修复气管缺损仍然是一项重大挑战。由于机械性能不匹配和抗炎性能有限，目前的支架无法实现最佳的气管修复。在本研究中，我们将天然植物来源的抗炎分子黄腐酚（XN）掺入可降解聚氨酯（PEUU）的主链中，以创建一种具有可定制机械性能和持续抗炎活性的多孔PEXUU支架。最初使用Materials Studio软件模拟以XN作为扩链剂和聚（ε-己内酯）作为软段合成PEXUU弹性体的可行性。力学测试证实，合成的PEXUU弹性体表现出优异的弹性和抗疲劳性，与天然气管的机械性能非常相似。然后通过热致相分离将PEXUU弹性体加工成多孔支架，该支架具有高孔隙率和良好的亲水性，同时在降解过程中以持续的方式提供持久的XN释放动力学。共培养研究表明，该支架不仅表现出良好的生物相容性并支持软骨再生，而且有效地下调促炎因子表达并促进M1巨噬细胞向M2表型极化。此外，实验表明植入PEXUU支架可显著减轻局部炎症并促进成熟软骨组织的形成。在兔气管窗口缺损模型中，该支架显著减少肉芽组织形成并保持管腔通畅，最终产生优异的修复效果。总之，XN本体改性的PEUU代表了一种双功能策略，将可定制的机械顺应性与持续的抗炎活性相结合。这种方法显著促进气管再生和修复，为临床应用提供了广阔前景。
