Dual-enzymatically crosslinked and injectable hyaluronic acid hydrogels for potential application in tissue...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Injectable hydrogels are valuable for minimally invasive biomedical applications.
• They serve as effective carriers for cells and drugs in tissue repair.
• Hyaluronic acid (HA) is a biocompatible polymer with potential in drug delivery.

Purpose of the Study:

• To develop a novel injectable hydrogel based on tyramine-modified hyaluronic acid (HT).
• To investigate the dual-enzymatic crosslinking of HT hydrogels using horseradish peroxidase (HRP) and galactose oxidase (GalOX).
• To evaluate the in vitro and in vivo properties of the developed HT hydrogel for potential biomedical applications.

Main Methods:

• Functionalization of hyaluronic acid with tyramine.
• Dual-enzymatic crosslinking of tyramine-modified hyaluronic acid using HRP and GalOX.
• Assessment of hydrogel injectability, cytocompatibility with mice bone marrow mesenchymal stem cells (BMSCs), and inflammatory response in vitro and in vivo.
• Evaluation of gelation time, swelling behavior, and degradation rate.

Main Results:

• The developed HT hydrogel demonstrated good injectability.
• Favorable cytocompatibility with BMSCs was observed.
• Low inflammatory response was confirmed through in vitro cytotoxicity assays and in situ subcutaneous injection studies.
• Tunable gelation time, swelling, and degradation properties were achieved by adjusting HT and GalOX concentrations.

Conclusions:

• The novel tyramine-modified hyaluronic acid hydrogel crosslinked enzymatically is biocompatible and injectable.
• The HT hydrogel exhibits tunable properties suitable for various biomedical applications.
• These findings suggest potential applications in three-dimensional stem cell culture and tissue engineering.