A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair In A Minipig Model In Vivo.
Liang GaoRiccardo BeninattoTamás OláhLars GoebelKe TaoRebecca RoelsSteffen SchrenkerJulianne GlommJagadeesh K VenkatesanGertrud SchmittEbrar SahinOla DahhanMauro PavanCarlo BarberaAlba Di LuciaMichael D MengerMatthias W LaschkeMagali CucchiariniDevis GalessoHenning MadryPublished in: Advanced healthcare materials (2023)
Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short-term safety and efficacy of two novel hyaluronic acid (HA)-triethylene glycol (TEG)-coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model. We hypothesize that HA-hydrogel-augmented microfracture (MFX) is superior to MFX in enhancing early cartilage repair, and that the molar degree of substitution and concentration of HA affects repair. We treat chondral full-thickness defects in the knees of adult minipigs with either (1) debridement (No MFX), (2) debridement and MFX, (3) debridement, MFX and HA hydrogel (30% molar derivatization, 30 mg/ml HA; F3) (MFX+F3), and (4) debridement, MFX and HA hydrogel (40% molar derivatization, 20 mg/ml HA; F4) (MFX+F4). After 8 weeks postoperatively, MFX+F3 significantly improves total macroscopic and histological scores compared with all other groups without negative effects, besides significantly enhancing the individual repair parameters "defect architecture", "repair tissue surface" (compared with No MFX, MFX), and "subchondral bone" (compared with MFX). These data indicate that photopolymerizable HA hydrogels enable a favorable metastable microenvironment promoting early chondrogenesis in vivo. This work also uncovers a mechanism for effective HA-augmented cartilage repair by combining lower molar derivatization with higher concentrations. This article is protected by copyright. All rights reserved.
Keyphrases
- hyaluronic acid
- drug delivery
- ms ms
- liquid chromatography tandem mass spectrometry
- tissue engineering
- stem cells
- drug release
- extracellular matrix
- body composition
- high resolution
- optical coherence tomography
- electronic health record
- gas chromatography
- bone mineral density
- solid phase extraction
- ultra high performance liquid chromatography
- high resolution mass spectrometry