Effect of a stabilized liquid ozone-containing formulation delivered through a hyaluronic acid/poly-D,L-lactide scaffold on early osteochondral repair in a rat model
In brief
Ozone-containing scaffold improves early cartilage repair scores in rats
At 45 days, rats given the ozone-containing scaffold had lower cartilage degeneration scores than rats with untreated defects or a scaffold alone. Cartilage damage area was smaller than in untreated defects, but not significantly smaller than with the scaffold alone. The animal study cannot isolate ozone's effect or show true cartilage regeneration.
- Journal
- Injury (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Turan Bilge Kızkapan, Sinan Oğuzkaya, Abdulhamit Mısır, Gökay Eken, Gökhan Sayer, Ömer Faruk Bayrakçıoğlu, et al.
- PMID
- 42826617
- DOI
- 10.1016/j.injury.2026.113744
Why clinicians should know about it
- Picked for Histology (top studies of the week, 4 October 2026): Scaffold histology shows cartilage repair
Abstract
BACKGROUND: Articular cartilage has limited intrinsic repair capacity, and osteochondral defects may progress to degenerative joint disease. Ozone has anti-inflammatory properties but is highly reactive and short-lived in gaseous form. This study evaluated whether a stabilized liquid ozone-containing formulation delivered through a hyaluronic acid/poly-D,L-lactide (HA/PDL) scaffold improves early histological repair of osteochondral defects. METHODS: Forty female Sprague-Dawley rats were randomly allocated to four groups (n = 10 each): healthy reference, untreated defect, HA/PDL scaffold, and HA/PDL scaffold impregnated with the stabilized liquid ozone-containing formulation. A 1-mm-diameter, 3-mm-deep osteochondral defect was created in the right femoral intercondylar region. Animals were euthanized on postoperative day 45. Histological repair was evaluated using the Modified Mankin score (0-14), and residual cartilage damage area was quantified in mm² on the index haematoxylin and eosin (H&E)-stained section using calibrated ImageJ analysis. RESULTS: All animals completed the study. Because the healthy reference group received zero scores for all histological variables, inferential analyses were restricted to the operated groups. Total Modified Mankin scores differed significantly among groups (p = 0.001), with the ozone-loaded scaffold group demonstrating lower scores than both the untreated defect group (p = 0.002) and the scaffold-only group (p = 0.006), whereas no difference was observed between the latter two groups (p = 1.000). Significant group differences were also observed for structure (p = 0.001) and tidemark integrity (p = 0.004). Residual cartilage damage area differed among the operated groups (p = 0.001) and was smaller in the ozone-loaded scaffold group than in the untreated defect group (p < 0.001), whereas the comparison with the scaffold-only group did not reach statistical significance (p = 0.169). CONCLUSIONS: The stabilized liquid ozone-containing formulation delivered through an HA/PDL scaffold was associated with improved early histological repair compared with untreated defects and yielded lower histological degeneration scores than scaffold implantation alone. Because the formulation comprised multiple components and no ozone-free vehicle control was included, these findings cannot be attributed specifically to ozone and should be interpreted as evidence of improved early histological repair rather than true cartilage regeneration. LEVEL OF EVIDENCE: Not applicable (Experimental animal study).
Abstract as published, via PubMed.
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