Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue

TLDR

Creating large 3‑D bone constructs with functional blood vessels remains a major challenge for repairing extensive bone defects. The study aims to use extrusion‑based bioprinting to fabricate microstructured bone‑like constructs that include perfusable vascular lumens. The authors printed GelMA‑based microstructures—a low‑methacryloyl GelMA cylinder for a perfusable lumen, GelMA cylinders with silicate nanoplatelets for osteogenesis, and VEGF‑conjugated GelMA for vascular spreading—and then seeded them with endothelial and mesenchymal stem cells in a natural hydrogel to create biomimetic matrices. The engineered constructs supported cell survival and proliferation, remained structurally stable for 21 days, and enabled local control of physical and chemical microniches and gradient formation.

Abstract

Fabricating 3D large‐scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion‐based direct‐writing bioprinting strategy is utilized to fabricate microstructured bone‐like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co‐culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMA LOW ) was printed. We also develop cell‐laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs.