A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo.

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. It is hypothesized 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. Chondral full-thickness defects in the knees of adult minipigs are treated with either 1) debridement (No MFX), 2) debridement and MFX, 3) debridement, MFX, and HA hydrogel (30% molar derivatization, 30 mg mL-1 HA; F3) (MFX+F3), and 4) debridement, MFX, and HA hydrogel (40% molar derivatization, 20 mg mL-1 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.

Future Aspects of Clinical Osteoarthritis Therapies in the Continuum of Translational Research. / Zukunftsaspekte der klinischen Arthrosetherapie im Kontinuum der translationalen Forschung.

Osteoarthritis (OA) affects a significant number of the world's adult population. In recent years different causal approaches to treat OA based on new translational knowledge have been developed. This review article provides, a brief overview of new findings on the pathophysiology and genetics and the interplay between biomechanics, pain and body weight. Current pharmacological and reconstructive surgical treatment options as well as studies on novel regenerative and molecular therapies of OA, such as applying NGF, FGF-18, TNF-α, Wnt signaling pathway inhibitors, and TGF-ß1 gene therapy are discussed. The basis of this work is a selective literature search in PubMed, ScienceDirect and Google Scholar. Selected new findings are discussed in the clinical perspective of OA.