Abstract

Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to their excellent biocompatibility. HA can be Ultraviolet (UV)-crosslinked by modification with methacrylic anhydride (HA-MA) and crosslinked by modification with 3,3′-dithiobis(propionylhydrazide) (DTP) (HA-SH) via click reaction. In the study presented in this paper, a 3D-bioprinted, double-crosslinked, hyaluronic-acid-based hydrogel for wound dressing was proposed. The hydrogel was produced by mixing HA-MA and HA-SH at different weight ratios. The rheological test showed that the storage modulus (G’) of the HA-SH/HA-MA hydrogel increased with the increase in the HA-MA content. The hydrogel had a high swelling ratio and a high controlled degradation rate. The in vitro degradation test showed that the hydrogel at the HA-SH/HA-MA ratio of 9:1 (S9M1) degraded by 89.91% ± 2.26% at 11 days. The rheological performance, drug release profile and the cytocompatibility of HA-SH/HA-MA hydrogels with loaded Nafcillin, which is an antibacterial drug, were evaluated. The wound dressing function of this hydrogel was evaluated by Live/Dead staining and CCK-8 assays. The foregoing results imply that the proposed HA-SH/HA-MA hydrogel has promise in wound repair applications.

Highlights

  • The human skin is the primary defense against the invasion of harmful external factors [1].Skin damage can cause serious health threats

  • After the hydrogel solutions were prepared according to the proportion given in Table 1, Nafcillin was added into each group to obtain a concentration of 5 mg/mL [42]

  • Is consistent with the resonance peak of DTP, indicating that the synthesis of Hyaluronic acid (HA)-SH is successful as a result of the presence of the conjugated thiol group

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Summary

Introduction

The human skin is the primary defense against the invasion of harmful external factors [1]. Hydrogel dressing is an effective material system to promote wound healing. It works by utilizing penicillin-binding proteins and inhibiting the cross-linking of cell wall peptidoglycan This antibiotic is useful to treat infections caused by methycillin-sensitive penicillinase-producing staphylococci. In order to be 3D bioprintable, HA has been chemically modified to spontaneously form gels, most commonly through disulfide, addition, hydrazide, enzymatic, and click reactions Among these modifications, thiol-modified HA (HA-SH) spontaneously, but slowly, crosslink in air to form a hydrogel; this gel can be dried to give a thin film or lyophilized to produce a porous sponge. In the study presented in this paper, a double-crosslinked network of HA-MA and HA-SH hydrogels were synthesized as a bioink for the 3D bioprinting of a wound dressing. Human dermal fibroblast (HDF) cells were used to test the wound healing function of the hydrogel, because HDF cells exist in the dermis of human skin and are one of the most important components of skin [35,36,37]

Materials
Synthesis of HA-SH
Synthesis of HA-MA
Preparation of the Bioink Encapsulating Cells
Characterization of the Hydrogel
Morphology of the Hydrogel
Swelling Test
In Vitro Degradation Test
2.10.1. Preparation of Cells
2.10.2. Preparation of Medium
2.10.3. CCK-8 Assay
2.11. In Vitro Drug Release Test
Synthesis of HA-SH and HA-MA
The Properties of the Hydrogels
In Vitro Degradation
Result
In Vitro Drug Release
Conclusions
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