An injectable aldehyded 1-amino-3,3-diethoxy-propane hyaluronic acid-chitosan hydrogel as a carrier of adipose derived stem cells to enhance angiogenesis and promote skin regeneration

We report an injectable aldehyded 1-amino-3,3-diethoxy-propane (ADEP)-hyaluronic acid (AHA)-chitosan (CS) hydrogel. This hydrogel can enhance wound healing by promoting cell migration, proliferation, granulation and angiogensis. During sol-gel transition, no chemical crosslinking agent was introduced and the structure of polysaccharide HA was grafted with a functional molecule, 1-amino-3,3-diethoxy-propane, but without using oxidation to break the HA structure as previously reported. Rheological tests showed the injectability and stability of this AHA-CS hydrogel. Full thickness skin defects (1 cm x 1 cm) were made on mice and the adipose derived stem cell loaded gel was tested in the healing-impaired wound. The AHA-CA hydrogel significantly accelerated wound closure, increased cell proliferation (Ki67 marker) and promoted keratinocyte migration (p63 marker). Histological examination demonstrated that the gel significantly advanced granulation tissue and capillary formation in the gel-treated wounds. mRNA expressions of angiogenesis (VEGF-A), chemotactic factors (SDF-1) and ECM-remodeling MMPs (MMP1 and MMP9) were also up-regulated in the hydrogel-treated wounds.