Biomimetic Hydrogel Scaffold Loaded With Guluronate Oligosaccharides Promotes Lung Tissue Regeneration and Alleviates Pulmonary Fibrosis.

In thoracic surgery, challenges in pulmonary tissue repair and regeneration remain a major concern. This study aimed to develop a biomimetic hydrogel scaffold, based on gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA), loaded with guluronate oligosaccharides (Oligo G) to promote pulmonary tissue repair and regeneration. The GelMA/HAMA hydrogel scaffold exhibited a porous microstructure resembling lung tissue, with excellent biocompatibility and biodegradability in both in vivo and in vitro settings, providing sufficient space for cell growth and attachment. Type II alveolar epithelial cells (RLE-6TN) cultured on the scaffold showed enhanced growth, whereas the scaffold restrained the activity of lung cancer A549 cells induced by TGF-β1. Western blot analysis confirmed the downregulation of TGF-β and Smad2/3 expression in A549 cells induced by TGF-β1. In vivo studies using rat models of acute lung injury (ALI) and mouse models of bleomycin (BLM)-induced pulmonary fibrosis demonstrated that the GelMA/HAMA hydrogel scaffold loaded with Oligo G promoted the repair of damaged lung tissue, alveolar regeneration, and angiogenesis after ALI. Moreover, it slowed the deterioration of pulmonary fibrosis and inflammation. The biomimetic GelMA/HAMA scaffold holds promise for promoting lung tissue repair after ALI and inhibiting pulmonary fibrosis progression.