Gelatin

Cell biology

Biotechnology

Polymer chemistry

Biology

Mesenchymal stem cell

Biomedical engineering

Metallurgy

Materials science

Surgery

Transplantation

Tissue engineering

Biochemistry

Biomaterial

In vivo

Nanotechnology

Anatomy

Self-healing hydrogels

In vitro

Biocompatibility

Medicine

Hyaluronic acid

Advanced Functional Materials

Clinical trials utilizing mesenchymal stem cells (MSCs) for severe vascular diseases have highlighted the need to effectively engraft cells and promote pro‐angiogenic activity. A functional material accomplishing these two goals is an ideal solution as spatiotemporal and batch‐to‐batch variability in classical therapeutic delivery can be minimized, and tissue regeneration would begin rapidly at the implantation site. Gelatin may serve as a promising biomaterial due to its excellent biocompatibility, biodegradability, and non‐immuno/antigenicity. However, the dissolution of gelatin at body temperature and quick enzymatic degradation in vivo have limited its use thus far. To overcome these challenges, an injectable, in situ crosslinkable gelatin was developed by conjugating enzymatically crosslinkable hydroxyphenyl propionic acid (GHPA). When MSCs are cultured in 3D in vitro or injected in vivo in GHPA, spontaneous endothelial differentiation occurs, as evidenced by marked increases in endothlelial cell marker expressions ( Flk1, Tie2, ANGPT1, vWF ) in addition to forming an extensive perfusable vascular network after 2‐week subcutaneous implantation. Additionally, favorable host macrophage response is achieved with GHPA as shown by decreased iNOS and increased MRC1 expression. These results indicate GHPA as a promising soluble factor‐free cell delivery template which induces endothelial differentiation of MSCs with robust neovasculature formation and favorable host response.

In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells