Injectable Hydrogel with Slow Degradability Composed of Gelatin and Hyaluronic Acid Cross-Linked by Schiff’s Base Formation

• Published in: Biomacromolecules Vol. 19; no. 2; pp. 288 - 297
• Main Authors: Hozumi, Takuro, Kageyama, Tatsuto, Ohta, Seiichi, Fukuda, Junji, Ito, Taichi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12.02.2018
• Subjects: adipic acid; aldehydes; angiogenesis; Animals; Cross-Linking Reagents - chemistry; crosslinking; gelatin; Gelatin - chemistry; Human Umbilical Vein Endothelial Cells - drug effects; Humans; hyaluronic acid; Hyaluronic Acid - analogs & derivatives; hydrogels; Hydrogels - chemical synthesis; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Male; Neovascularization, Physiologic - drug effects; oxidation; porosity; Rats; Rats, Sprague-Dawley; Schiff Bases - chemistry; storage modulus; Swine; Tissue Scaffolds - chemistry
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/acs.biomac.7b01133

We developed an injectable gelatin/hyaluronic acid hydrogel with slow degradability, which consisted of carbohydrazide-modified gelatin (Gel-CDH) and hyaluronic acid monoaldehyde (HA-mCHO). Gel-CDH/HA-mCHO hydrogels were degraded much more slowly in phosphate-buffered saline than the other Schiff’s base cross-linked gelatin/hyaluronic acid hydrogels that were comprised of native gelatin, adipic acid dihydrazide-modified gelatin, or hyaluronic acid dialdehyde because of stable Schiff’s base formation between aldehyde and carbohydrazide groups, and suppression of ring-opening oxidation by monoaldehyde modification. This prolonged degradation would be suitable for inducing angiogenesis. Therefore, the Gel-CDH/HA-mCHO hydrogels were sufficiently stable during the angiogenesis process. In addition, the hydrogel had a pore size of 15–55 μm and a shear storage modulus of 0.1–1 kPa, which were appropriate for scaffold application. Ex vivo rat aortic-ring assay demonstrated the concentration dependency of microvascular extension in the Gel-CDH/HA-mCHO hydrogel. These results demonstrated the potential usefulness of Gel-CDH/HA-mCHO hydrogel for tissue-engineering scaffolds.