Guiding vascular infiltration through architected GelMA/PEGDA hydrogels: an in vivo study of channel diameter, length, and complexity

Abstract

Organ shortages for transplantation in the United States impact over 100 000 patients, with 17 dying daily due to the lack of available organs. This growing need is exacerbated by the limited functionality and disease risk of donated organs. Tissue-engineered organs present a promising alternative, requiring optimized scaffold architecture and cell integration. Vascular networks within organs are essential for supplying oxygen and nutrients to cells, with a critical distance between blood vessels and surrounding tissue to allow effective diffusion. Various microfabrication techniques, such as electrospinning, freeze-drying, and gas foaming, have been employed to develop engineered organs. However, these techniques often lack the complexity needed to support vascularization. 3D bioprinting, particularly digital light projection (DLP)-based stereolithography, offers a solution by enabling high-resolution control of both external and internal architectures. Gelatin methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogels have shown potential for tissue integration in simple structures but require further optimization for vascularization in more complex constructs. This study utilizes DLP to 3D bioprint GelMA/PEGDA hydrogels, exploring various channel designs to enhance tissue infiltration and vascularization in rodent models, providing a potential platform for cell and tissue transplantation. We demonstrate that GelMA/PEGDA hydrogels are mechanically robust, biocompatible, and support in vivo vascular infiltration. Channel diameter significantly influenced vascularization, with 1 mm channels yielding the highest infiltration, while channel length had minimal impact. Among five tested architectures, one design (GEO3) promoted the greatest vascular ingrowth, establishing a tunable hydrogel platform for prevascularized tissue engineering applications.