Methacrylated Pulmonary dECM-Enriched GelMA Bioinks Promote Endothelialization and Angiogenesis in 3D Printed Tubular Constructs

Abstract

In tissue engineering, developing biomimicking vascular tissue constructs is still significantly challenging due to the tubular architecture of the vessels and the limited availability of inexpensive biomaterials that can support effective endothelialization and angiogenesis. This study presents a robust protocol for designing 3D printed vascular tissue constructs composed of gelatin methacrylate (GelMA) and methacrylated pulmonary decellularized extracellular matrix (dECMMA) composite biomaterial ink. The pepsin-digested pulmonary dECM was identified with crucial ECM proteins responsible for blood vessel and circulatory system development, including collagen, fibrillin-1, annexin A2, and S100A11. The methacryloyl functionalization of dECM to form dECMMA was enabled by covalent crosslinking with GelMA to attain an inexpensive biomaterial ink that can support effective endothelialization and angiogenesis. Structurally intact 3D printed GelMA-dECMMA scaffolds, produced using the Suspended Layer Additive Manufacturing (SLAM) technique, showed improved endothelial cell attachment, proliferation, and organisation into vessel-like structures, strongly outperforming GelMA alone in promoting angiogenesis. Our results demonstrate the GelMA-dECMMA biomaterial ink's ability to create sophisticated biomimetic vascular models, which are promising for disease modelling and regenerative medicine.