Tuncer Sema, Subasi Can Secil, Akel Bilgic Hayriye, Kilic Busra, Gunal Gulcin, Aydin Halil Murat, Karaaslan Cagatay
Institute of Science and Centre of Bioengineering, Bioengineering Division, Hacettepe University, Cankaya, Ankara 06800, Türkiye.
Faculty of Science, Department of Biology, Molecular Biology Section, Hacettepe University, Cankaya, Ankara 06800, Türkiye.
ACS Omega. 2025 Aug 21;10(35):39693-39705. doi: 10.1021/acsomega.5c03198. eCollection 2025 Sep 9.
Chronic airway diseases represent a significant global health challenge, and reliable model systems are essential for elucidating the molecular mechanisms underlying these conditions. Although air-liquid interface (ALI) culture systems are among the most effective models for studying airway epithelial cells under physiological conditions, the nonbiodegradable membranes commonly used in current systems present certain limitations. In the present study, biodegradable poly-(l-lactic acid) (PLLA) and poly-(ε-caprolactone) (PCL) nanofiber membranes were fabricated using the electrospinning technique, and novel transwell membrane systems were developed. Optimization studies revealed that the nanofiber diameters ranged between 50 and 275 nm, forming a structure closely resembling the native lung extracellular matrix. Degradation analyses indicated that PLLA and PCL membranes remained structurally stable for up to six months, making them suitable for long-term airway modeling applications. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy confirmed the chemical stability of the membranes. Additionally, cell culture assays demonstrated high cell viability and strong cellular adhesion. Immunocytochemical analysis revealed β-tubulin expression in bronchial epithelial cells differentiated on the membranes, indicating successful epithelial maturation. These findings suggest that biodegradable membranes provide a promising platform for airway modeling. Furthermore, the use of biodegradable membranes is expected to address a critical need by accurately mimicking the tracheal and bronchial architecture as submucosal tissue analogues, thereby advancing the development of preclinical airway tissue graft constructs.
慢性气道疾病是一项重大的全球健康挑战，可靠的模型系统对于阐明这些疾病背后的分子机制至关重要。尽管气液界面（ALI）培养系统是在生理条件下研究气道上皮细胞最有效的模型之一，但当前系统中常用的不可生物降解膜存在一定局限性。在本研究中，使用静电纺丝技术制备了可生物降解的聚（L-乳酸）（PLLA）和聚（ε-己内酯）（PCL）纳米纤维膜，并开发了新型的Transwell膜系统。优化研究表明，纳米纤维直径在50至275纳米之间，形成了与天然肺细胞外基质非常相似的结构。降解分析表明，PLLA和PCL膜在长达六个月的时间内结构保持稳定，使其适用于长期气道建模应用。衰减全反射傅里叶变换红外（ATR-FTIR）光谱证实了膜的化学稳定性。此外，细胞培养试验显示细胞活力高且细胞粘附性强。免疫细胞化学分析显示在膜上分化的支气管上皮细胞中有β-微管蛋白表达，表明上皮细胞成功成熟。这些发现表明，可生物降解膜为气道建模提供了一个有前景的平台。此外，使用可生物降解膜有望通过精确模拟气管和支气管结构作为粘膜下组织类似物来满足一项关键需求，从而推动临床前气道组织移植构建体的发展。
