Neovascularization Stimulating Hydrogels for Regenerative Medicine

Abstract

Introduction Neovascularization of implants used as scaffolds is crucial for the regeneration of large tissue defects. Hence, the formation of vascular networks is of utmost importance. Photocrosslinkable hydrogels show promise as matrix for the ingrowth of neo-vessels. We integrated the mimicry of placenta, a highly vascularized organ, within gelatin (Gel)-hydrogels. Different Gel-modifications, including Gel-norbornene (Gel-NB) [1] and Gel-allyl glycidyl ether (Gel-AGE) [2] were in situ crosslinked enabling fabrication of complex structures either by extrusion-based 3D-bioprinting or by two-photo-polymerization.[3] Methods Gel was modified with 5-norbornene-2,3-dicarboxylic anhydride,N-hydroxysuccinimide-activated 5-norbornene-2-carboxylic acid (Gel-NBs), or allyl glycidyl ether (Gel-AGE) with degrees of modification. Hydrogel formation was monitored by photorheology using lithium phenyl-2,4-6-trimethylbenzoylphosphinate, as photoinitiator and D,L-dithiothreitol or ethoxylated trimethylolpropane tri(3-mercaptopropionate) as crosslinker in aqueous solution (2.5-10 wt%).[4]. Results Mechanical properties (shear moduli 10-1000 Pa) and swellability (5-40 fold) of the hydrogels depend on the type/degree of modification. Hydrogel vascular network formation with HUVECs was observed when placenta-specific factors were incorporated. Discussion and Conclusions The formation of vascular networks could be observed with the prepared hydrogels. For the 3D fabrication of vascularization promoting hydrogel constructs, suitable system is to be found by variation of parameter (modification, crosslinker, gel content etc.).