Assessing Angiogenic Properties In Vitro or In Ovo of Pre‐Crosslinked Alginate‐Dialdehyde‐Gelatin Hydrogels Incorporating Boron‐Doped Mesoporous Bioactive Glass Particles

In this study, the influence of boron (B)‐doped silicate‐based 65%SiO 2 –0%CaO–15%B 2 O 3 (mol% [15B]) mesoporous bioactive glass nanoparticles (MBGN) blended in cast and 3D printed pre‐crosslinked alginate‐dialdehyde‐gelatin (ADA‐GEL) constructs is examined, both in vitro and in ovo in the chick chorioallantoic membrane (CAM) model. Hydrogels such as ADA‐GEL can be further enhanced by incorporating bioactive glasses (BGs) releasing ions targeting physiological pathways. The high biocompatibility, osteo‐ and angiogenic activity of boron‐doped silicate‐based BG compositions point to boron for the developing field of vascularized tissue engineering. The addition of 15B at 2% w/v leads to cell death in the case of human umbilical vein endothelial cells (HUVECs). Addition of 0.5% and 1% 15B does not change the sprouting of HUVEC spheroids in ADA‐GEL. Interestingly, the main variability regarding HUVEC sprouting is shown between cast and 3D printed spheroids. Diffusion kinetics of ADA‐GEL show no difference with and without MBGNS. The biocompatibility of 15B MBGNs is proved in ovo, however, no signs of neovascularization are observed. The integration with the CAM is demonstrated using a human embryonic kidney (HEK‐293) reporter cell line. Taken together, it is concluded that modifying ADA‐GEL with 15B does not improve its angiogenic characteristics in ovo, at concentrations <2%.