Tamás Oláh

Purpose Elucidating subchondral bone remodeling in preclinical models of traumatic meniscus injury may address clinically relevant questions about determinants of knee osteoarthritis (OA). Methods Studies on subchondral bone remodeling in larger animal models applying meniscal injuries as standardizing entity were systematically analyzed. Of the identified 5367 papers reporting total or partial meniscectomy, meniscal transection or destabilization, 0.4% (in guinea pigs, rabbits, dogs, minipigs, sheep) remained eligible. Results Only early or mid‐term time points were available. Larger joint sizes allow reporting higher topographical details. The most frequently reported parameters were BV/TV (61%), BMD (41%), osteophytes (41%) and subchondral bone plate thickness (39%). Subchondral bone plate microstructure is not comprehensively, subarticular spongiosa microstructure is well characterized. The subarticular spongiosa is altered shortly before the subchondral bone plate. These early changes involve degradation of subarticular trabecular elements, reduction of their number, loss of bone volume and reduced mineralization. Soon thereafter, the previously normal subchondral bone plate becomes thicker. Its porosity first increases, then decreases. Conclusion The specific human topographical pattern of a thinner subchondral bone plate in the region below both menisci is present solely in the larger species (partly in rabbits), but absent in rodents, an important fact to consider when designing animal studies examining subchondral consequences of meniscus damage. Large animal models are capable of providing high topographical detail, suggesting that they may represent suitable study systems reflecting the clinical complexities. For advanced OA, significant gaps of knowledge exist. Future investigations assessing the subchondral bone in a standardized fashion are warranted.

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.