3D printed alginate/gelatin-based porous hydrogel scaffolds to improve diabetic wound healing

Diabetic wounds are difficult to heal due to hampered vascularization and tissue regeneration. Wound dressings need frequent replacement and show limited effects on guiding tissue repair. Here, bio-inks containing sodium alginate (SA), oxidized sodium alginate (OSA), gelatin (Gel) and CaCO 3 microspheres were prepared. To increase the printability, all bio-inks were pre-crosslinked with calcium ions (Ca 2 + ). Porous hydrogel scaffolds with 4.43 +/- 0.14 mu m 2 pore area and 184 +/- 25 mu m line diameter were fabricated via 3D printing. After lyophilization and swelling in PBS (pH 6.4), SA/OSA/Gel scaffold showed more excellent structural stability than SA and SA/Gel, which was attributed to the Schiff base reaction between OSA and Gel. NIH-3T3 cells on SA/OSA/Gel proliferated faster and showed better spreading morphology than those on SA and SA/Gel. After placed onto full-thickness wounds on SD rat back, SA/OSA/Gel scaffold guided tissue growth, integrated well with the regenerated tissue and accelerated wound healing, which promoted angiogenesis and showed 93.0 +/- 2.5% of collagen deposition between degraded fragments of hydrogel scaffold. Taken together, porous hydrogel scaffolds fabricated via 3D printing bio-inks composed of SA, OSA, Gel and CaCO 3 provide a potential strategy to improve diabetic wound healing.