A preclinical large-animal evaluation of a 3D bioprinted bionic pancreatic tissue model built on simplified vascular...

Three-dimensional (3D) bioprinting enables the fabrication of complex tissue constructs with integrated vascular architectures, offering promising applications in transplantation. It is commonly assumed that dense, pre-formed microvascular networks are required to ensure survival and function of bioprinted organs immediately after implantation. Thisin vivostudy aimed to evaluate the feasibility of bioprinting and transplanting a vascularized pancreatic tissue construct featuring a single perfusable vessel in a porcine model, with a focus on maintaining stable perfusion and supporting post-transplantation microvascular development. The study included 14 pigs, in which a 3D-bioprinted construct was transplanted and connected to the iliac artery or abdominal aorta. Two vascular connection strategies were evaluated: the Decell group (n= 5), using decellularized and recellularized external vessels for anastomosis, and the Bionic group (n= 9), using a vascular prosthesis. Immediate perfusion was achieved in all transplanted constructs. Three animals from the Bionic group completed a 4 week follow-up period. Computed tomography imaging and histopathological analyses demonstrated sustained perfusion of the constructs and progressive development of microvascular structures within the bioprinted tissue over time. These findings demonstrate the feasibility of fabricating and transplanting a perfusable, mechanically stable, bioprinted pancreatic tissue construct capable of supportingin vivovascular remodeling without a pre-fabricated dense capillary network. This work provides a preclinical proof-of-feasibility for simplified vascular design strategies in bioprinted tissue constructs and supports their further development toward translational applications.