Injectable MMP-Responsive Nanotube-Modified Gelatin Hydrogel for Dental Infection Ablation

Abstract

A photocrosslinkable gelatin methacryloyl (GelMA) hydrogel has been widely examined in regenerative engineering because of its good cell–tissue affinity and degradability in the presence of matrix metalloproteinases. A halloysite aluminosilicate nanotube (HNT) is a known reservoir for the loading and sustained delivery of therapeutics. Here, we formulate injectable chlorhexidine (CHX)-loaded nanotube-modified GelMA hydrogel that is cytocompatible and biodegradable and provides sustained release of CHX for infection ablation while displaying good biocompatibility. The effects of HNTs and CHX on hydrogel degradability and mechanical properties, as well as on the kinetics of CHX release, and on the antimicrobial efficacy against oral pathogens were systematically assessed. Cytocompatibility in stem cells from human exfoliated deciduous teeth and inflammatory response in vivo using a subcutaneous rat model were determined. Our hydrogel system, that is, (CHX)-loaded nanotube-modified GelMA showed minimum localized inflammatory responses, supporting its ability for drug delivery applications. Moreover, we showed that the incorporation of CHX-loaded nanotubes reduces the mechanical properties, increases the swelling ratio, and diminishes the degradation rate of the hydrogels. Importantly, the presence of CHX-loaded nanotubes inhibits bacterial growth with minimal cell toxicity. Our findings provide a new strategy to modify GelMA hydrogel with chlorhexidine-loaded nanotubes for clinical use as an injectable drug delivery strategy for dental infection ablation.

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

“…Nanoparticles were also developed with triggered disassembly or morphology change to improve site-specific delivery of drugs to the tumor site [262,263]. A gelatin-albumin (Gel-Alb) hybrid nanoparticle was generated and evaluated for its drug efficacy as an anti-cancer drug delivery system in a panel of subtype-specific breast cancer cell lines.…”

Cyanobacteria-based self-oxygenated photodynamic therapy for anaerobic infection treatment and tissue repair

“…GelMA hydrogel also has been used to photo-crosslink into a contact lens for corneal administration, and also for in situ crosslinking on the surface of the gingival infection site [ 52 , 53 ]. Considering the poor adhesion and the short residence time of CeCyan-Cu 5.4 O in the following anaerobic infectious keratitis and periophthalmitis, the widely recognized GelMA hydrogel with high biocompatibility and large pore size was used to encapsulate CeCyan-Cu 5.4 O [ 54 ]. Injectable GelMA hydrogel formed with 65% substitution degree of MA after photo-crosslinking ( Fig.…”

Programmable Building of Radially Gradient Nanofibrous Patches Enables Deployment, Bursting Bearing Capability, and Stem Cell Recruitment

“…[ 32,33 ] It is envisioned that the overexpression of MMPs in the inflammatory site after skin injury would excite an “on‐demand” delivery of anti‐inflammatory drug, since the MMPs can hydrolyze gelatin into polypeptides, peptides, and amino acids actively (Figure 4b). [ 34,35 ] The chemical structure of GelMA‐coatd GF‐9 patch was examined via Fourier transform infrared spectrometer (FTIR) (Figure S4, Supporting Information). The characteristic peak of acry‐lamide at 3315.40 cm −1 was observed, indicating the grafting of GelMA.…”