## 3 General Properties of Hyaluronic Acid-Catechol
### Tissue Adhesive Properties  
HA has anti-adhesive properties; therefore, HA-based physical barriers have been developed to prevent post-surgical adhesion. However, the conjugation of catechol groups  
Figure 1: (**a**) Synthesis and chemical structures of hyaluronic acid (HA)–catechol. (**b**) \({}^{1}\)H NMR and (**c**) UV–Vis spectra of HA–catechol.  
to HA significantly increases the adhesiveness of HA-catechol to tissues. As mentioned, the oxidized catechol groups (i.e., catechol quinone) can covalently react with the amine or thiol groups that are abundantly found in native tissues, including proteoglycan structures, resulting in superior tissue adhesive properties. The tissue adhesive properties of HA-catechol are commonly measured with a lap shear test using animal skin, such as chicken or porcine skin (Figure 2a). In addition, post-crosslinking of HA-catechol adhesives is carried out prior to its use on skin or dermal tissues to improve tissues' adhesion properties in general. The adhesive stress withstood by joint chicken skins in the presence of HA-catechol hydrogels is approximately 10 kPa, which is far greater than that bore when using methacrylated HA hydrogels (Figure 2b) [52]. In addition, tissue adhesive properties are improved by the addition of an oxidative intermolecular crosslink agent (NaIO\({}_{4}\)) and by an increase of DS in HA-catechol. The maximum adhesive strength is 90.0 \(\pm\) 6.7 kPa when using HA-catechol with high DS (0.45) at a molar ratio of 1:2 (catechol/NaIO\({}_{4}\)). Moreover, the addition of Fe\({}^{3+}\) ions to the hydrogels increases the adhesive stress of HA-catechol. The detachment stress of hydrogels containing HA-catechol/Fe\({}^{3+}\) complexes is 14.8 \(\pm\) 0.9 kPa, while that of an HA-catechol solution is 0.9 \(\pm\) 0.5 kPa, measured using mouse subcutaneous tissues [47].  
HA-catechol-based composite materials also show excellent adhesive properties. For instance, HA-catechol and Pluronic F127 (16 wt%) composite hydrogels show excellent stability with approximately 10-fold greater adhesive strength (-7.2 kPa) than HA-catechol alone (-1.7 kPa) [48]. HA-catechol/PVA (Polyvinyl alcohol) hydrogel composite films can be used as mucoadhesive films for the treatment of oral candidiasis [49]. HA-catechol/PVA hydrogels have a high detachment force of approximately 0.23 N, which was measured using a bovine buccal membrane. HA-catechol/PLL (poly-l-lysine) hydrogels enzymatically crosslinked with horseradish peroxidase (HRP) with H\({}_{2}\)O\({}_{2}\) showed a significant improvement in adhesive strength, from 20.8 kPa to 33.8 kPa [39]. Therefore, HA-catechol is useful for long-term tissue adhesion and may have great potential for use in biomedical applications. Furthermore, the tissue adhesiveness of HA-catechol may prevent the malposition or movement of the HA-based materials on the targeted tissue surfaces.  
Figure 2: (**a**) Schematic illustration of a lap shear tissue adhesion test. (**b**) Average adhesive stress (kPa) of methacrylated HA (MeHA) and HA–catechol (HA-Cat) hydrogels (**\(p<0.01\)). Reprinted with permission from [52]. Copyright © 2019 Elsevier.