Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis

Abstract

Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.

Is the cortical capillary renamed as the transcortical vessel in diaphyseal vascularity?

“…It acts as a reservoir of minerals and blood cells. Unlike the connective tissue, which has meager vascularity, the bone is highly vascularized except at the growth plate and the articular cartilage (Anada et al, 2019; Fajardo, 2017). Like other tissues, it also has a closed circulatory system.…”

Construction of higher-order cellular microstructures by a self-wrapping co-culture strategy using a redox-responsive hydrogel

“…However, designing large 3D cellular microstructures while maintaining cell viability still remains a challenge. Based on the ability to distribute oxygen, metabolites and nutrient, presenting endothelial cells are favorable in tissue engineering fileld 48 , especially for promoting vascularization in the 3D cell culture [53][54][55] . The incorporation of endothelial cells (e.g., HUVECs) was thus used in an attempt to improve the cellular function of the wrapped structure (triple co-culture, Fig.…”

Advances on Bone Substitutes through 3D Bioprinting

“…Moreover, Lv and colleagues [ 142 ] proved that a prolonged release of VEGF through 3D bioprinting improves both osteogenesis and angiogenesis. Anada et al [ 143 ] obtained a highly vascularized biomimetic hydrogel suitable for BTE applications, by creating a dual ring bone-mimetic construct, composed of a GelMA/octacalcium phosphate in the external ring, which stimulated bone formation, while the central ring of GelMA loaded with HUVECs promoted angiogenesis within the construct. Fedorovich et al [ 144 ] described how to effectively bioprint vascularized bone tissue by using alginate hydrogels and Matrigel TM , seeded with endothelial cell precursors and MSCs, thus creating a heterocellular and multimaterial construct.…”