Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, 710038, China; Department of Cardiothoracic Surgery, Central Theater Command General Hospital of Chinese People's Liberation Army, Wuhan, Hubei, 430070, China.
Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, 710038, China; Department of General Surgery, The 991st Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Xiangyang, Hubei, 441000, China.
Biomaterials. 2023 Sep;300:122208. doi: 10.1016/j.biomaterials.2023.122208. Epub 2023 Jun 17.
In this study, a cell-free tissue-engineered tracheal substitute was developed, which is based on a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl (GelMA) hydrogel, with transforming growth factor-β1 (TGF-β) and stromal cell-derived factor-1α (SDF-1) sequentially embedded, to facilitate cell recruitment and differentiation toward chondrocyte-phenotype. TGF-β was loaded onto polydopamine particles, and then encapsulated into the GelMA together with SDF-1, and called G/S/P@T, which was used to coat 3D-printed PCL scaffold to form the tracheal substitute. A rapid release of SDF-1 was observed during the first week, followed by a slow and sustained release of TGF-β for approximately four weeks. The tracheal substitute significantly promoted the recruitment of mesenchymal stromal cells (MSCs) or human bronchial epithelial cells in vitro, and enhanced the ability of MSCs to differentiate towards chondrocyte phenotype. Implantation of the tissue-engineered tracheal substitute with a rabbit tracheal anterior defect model improved regeneration of airway epithelium, recruitment of endogenous MSCs and expression of markers of chondrocytes at the tracheal defect site. Moreover, the tracheal substitute maintained airway opening for 4 weeks in a tracheal full circumferential defect model with airway epithelium coverage at the defect sites without granulation tissue accumulation in the tracheal lumen or underneath. The promising results suggest that this simple, cell-free tissue-engineered tracheal substitute can be used directly after tracheal defect removal and should be further developed towards clinical application.
在这项研究中，开发了一种无细胞组织工程气管替代物，它基于 3D 打印的聚己内酯支架，该支架涂有明胶甲基丙烯酰（GelMA）水凝胶，依次嵌入转化生长因子-β1（TGF-β）和基质细胞衍生因子-1α（SDF-1），以促进细胞募集和向软骨细胞表型分化。TGF-β被加载到聚多巴胺颗粒上，然后与 SDF-1 一起封装在 GelMA 中，并称为 G/S/P@T，用于涂覆 3D 打印的 PCL 支架以形成气管替代物。在第一周内观察到 SDF-1 的快速释放，随后 TGF-β的缓慢和持续释放约四周。气管替代物在体外显著促进间充质基质细胞（MSCs）或人支气管上皮细胞的募集，并增强 MSCs 向软骨细胞表型分化的能力。在兔气管前缺损模型中植入组织工程气管替代物，可改善气道上皮的再生、内源性 MSCs 的募集以及气管缺损部位软骨细胞标志物的表达。此外，气管替代物在气管全周缺损模型中保持气道通畅 4 周，气道上皮覆盖在缺损部位，气管腔或气管腔下无肉芽组织积聚。有前途的结果表明，这种简单的无细胞组织工程气管替代物可以在气管缺损切除后直接使用，应进一步开发用于临床应用。
