Injectable and Self-Healing Hydrogels with Double-Dynamic Bond Tunable Mechanical, Gel–Sol Transition and Drug Delivery Properties for Promoting Periodontium Regeneration in Periodontitis

Abstract

Injection of a hydrogel loaded with drugs with simultaneous anti-inflammatory and tissue regenerating properties can be an effective treatment for promoting periodontal regeneration in periodontitis. Nevertheless, the design and preparation of an injectable hydrogel with self-healing properties for tunable sustained drug release is still highly desired. In this work, polysaccharidebased hydrogels were formed by a dynamic cross-linked network of dynamic Schiff base bonds and dynamic coordination bonds. The hydrogels showed a quick gelation process, injectability, and excellent self-healing properties. In particular, the hydrogels formed by a double-dynamic network would undergo a gel−sol transition process without external stimuli. And the gel−sol transition time could be tuned by the double-dynamic network structure for in situ stimuli involving a change in its own molecular structure. Moreover, the drug delivery properties were also tunable owing to the gel−sol transition process. Sustained drug release characteristics, which were ascribed to a diffusion process, were observed during the first stage of drug release, and complete drug release owing to the gel−sol transition process was achieved. The sustained drug release time could be tuned according to the double-dynamic bonds in the hydrogel. The CCK-8 assay was used to evaluate the cytotoxicity, and the result showed no cytotoxicity, indicating that the injectable and self-healing hydrogels with double-dynamic bond tunable gel−sol transition could be safely used in controlled drug delivery for periodontal disease therapy. Finally, the promotion of periodontal regeneration in periodontitis in vivo was investigated using hydrogels loaded with ginsenoside Rg1 and amelogenin. Micro-CT and histological analyses indicated that the hydrogels were promising candidates for addressing the practical needs of a tunable drug delivery method for promoting periodontal regeneration in periodontitis.

Injectable Adhesive Self-Healing Multiple-Dynamic-Bond Crosslinked Hydrogel with Photothermal Antibacterial Activity for Infected Wound Healing

“…OHAdop was synthesized through dopamine-modified OHA to introduce catechol groups. Aldehyde groups could be successfully introduced into the HA backbone via NaIO 4 oxidation, as was reported in our previous literature . To improve the adhesive properties, catechol groups were added to the OHA backbone through an EDCI/NHS condensation reaction (see Figure a) with dopamine hydrochloride.…”

“…The changes in peaks at 1730 and 1654 cm –1 in the FTIR spectrum (Figure S1d, Supporting Information) indicated the formation of an imine CN bond in the hydrogel and the absence of an aldehyde group in OHAdop . The gelation time decreased with the introduction of GG/borax into the OHAdop/GC-based hydrogel, indicating additional dynamic borate/didiol bond formation in the hydrogels.…”

“…Aldehyde groups could be successfully introduced into the HA backbone via NaIO 4 oxidation, as was reported in our previous literature. 63 To improve the adhesive properties, catechol groups were added to the OHA backbone through an EDCI/NHS condensation reaction (see Figure 1a) with dopamine hydrochloride. As seen in Video S1 and Video S2, the OHAdop3% + GC3% hydrogel could adhere to fingers with stretching, while the OHA3% + GC3% hydrogel could not adhere to fingers, which proved improved adhesive properties with the modification of OHA with the catechol group.…”

“…Synthesis and Characterization of OHAdop. Oxidized hyaluronic acid (OHA) was synthesized according to our previous work 63 with a little modification. Briefly, 5 g of HA was dissolved in 200 mL of deionized water under vigorous stirring, and then 0.5 M NaIO 4 in deionized water (15 mL) was added dropwise to the above solution and the mixture was continued to stir in the dark for 2 h at 25 °C.…”

Inosine‐Based Supramolecular Hydrogel for Highly Efficient PD‐L1 Blockade Therapy via Mediating CD8+ T Cells

“…Dynamic covalent bonds are the basis of a gel–sol transition, which make the injectability of hydrogel possible. [ 27 ] A variety of dynamic covalent bonds have been introduced into the design of supramolecular hydrogels, including imine bonds, borate ester bonds, Diels–Alder reactions, arylhydrazone bonds, oxime bonds, and disulfide bonds. [ 28 ] The formation of dynamic borate esters in the IPBisoG hydrogel suggests its potential to be employed as an injectable hydrogel for local therapeutic purposes.…”