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Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints.

ABSTRACT: The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O'Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects.

SUBMITTER: Shi C

PROVIDER: S-EPMC8159088 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective:Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone which has the ability to treat and activate the CLRN1 pathway to play a pivotal role in hearing loss and hair cell function. To investigate the therapeutic effect of ART in hearing loss induced by gentamicin (GM), an ART-loaded poly(ethylene glycol)-b-poly(?-caprolactone) mPEG-PCL nanoparticle-based photosensitive hydrogel was developed and tested in this study. Materials and Methods:Artemisinin-loaded mPEG-PCL nanoparticles (mPEG-PCL-ART-NPs) were prepared by a double emulsion method and the formulation was optimized by an orthogonal experimental design. The particle size, zeta potential, morphology and in vitro dissolution of the mPEG-PCL-ART-NPs were well characterized. Biocompatibility of the mPEG-PCL-ART-NPs were tested on HeLa cells with an MTT assay. The photo-crosslinkable biodegradable gelatin methacrylate (GelMA) hydrogel was prepared and its physicochemical properties (such as substitution, photocrosslinking efficiency, cell viability morphology, mechanical and swelling properties) were evaluated. Finally, mPEG-PCL-ART-FITC-NPs, loaded mPEG-PCL-ART-NPs, and loaded mPEG-PCL-ART-NPs-GelMA hydrogels were fabricated and a GM toxicity-induced guinea pig ear damage model was established to determine the effectiveness of the materials on returning auditory function and cochlea pathomorphology. Results:The zeta potential of the mPEG-PCL-ART-NPs was about -38.64 ± 0.21 mV and the average size was 167.51 ± 1.87 nm with an encapsulation efficacy of 81.7 ± 1.46%. In vitro release studies showed that the mPEG-PCL-ART-NPs possessed a sustained-release effect and the MTT experiments showed good biocompatibility properties of the drug-loaded nanoparticles. The results indicated that the 5% GelMA with MA-4% hydrogel had a better crosslinking density and 3D structure for drug loading and drug delivery than controls. Skin penetration results showed that the mPEG-PCL-ART-NPs increased adhesive capacity and avoided fast diffusion in the skin. Most importantly, auditory brainstem response results indicated that the mPEG-PCL-ART-NPs-GelMA hydrogel alleviated hearing loss induced by GM. Conclusion:These results suggested that the presently fabricated mPEG-PCL-ART-NPs-GelMA hydrogels are promising formulations for the treatment of hearing loss induced by GM and lay the foundation for further clinical research of inner ear induction therapy.

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Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints.

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