Animal Models

P014 - Hyaluronan photocrosslinked hydrogels for improved osteochondral repair: a 1-year pre-clinical study on a mini-pig model

Disclosure
R. Beninatto, C. Barbera, M. Pavan and D. Galesso are full-time employees at Fidia Farmaceutici S.p.A.
Presentation Topic
Animal Models
Poster Rating
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Abstract

Purpose

Hyaluronic acid (HA) hydrogels play a crucial role in the development of new biomaterials for cartilage regeneration. In the present study, a solution of a photocrosslinkable coumarin‑HA derivative [Beninatto et al., MSEC 2019] was applied to chondral lesions in a mini-pig model of cartilage defect, and its efficacy and safety for cartilage repair was assessed at 1 year.

Methods and Materials

Standardized full-thickness chondral defects (Ø: 5 mm) were created in the trochlear groove of mini-pigs and treated by (1) debridement, (2) debridement and microfracture (MFX), (3-4) debridement, MFX, and two different prototypes of photocrosslinkable coumarin‑HA solutions (p30 and p40), which were crosslinked through a 5 min UV irradiation (λ=365 nm). The osteochondral repair was assessed at 1 year postoperatively using established macroscopic, histological, immunohistochemical, and Micro-CT analyses [Gao et al., Sci. Rep. 2016]. For the histological evaluation, sections were stained with Safranin-O/Fast Green protocol. A total of 8 sections per defect were analyzed applying the cartilage repair score described by Sellers et al. [J. Bone Joint Surg. Am. 1997].

Results

In vivo application of our novel photocrosslinkable hyaluronan hydrogels is safe and caused no material-related side effects. Semi-quantitative histological analysis of cartilage revealed that hydrogels treatment yields good filling, adjacent integration, and chondrocyte induction in the surgically induced cartilage defects. No difference was detected in macroscopic scoring between p30 and p40 treated groups and hydrogel application yielded no biomechanical disturbance on the subarticular spongiosa. Improved new subchondral bone formation was observed in hydrogel treated defects, compared to MFX; furthermore, p40 yielded higher specific bone surface (BS/BV) than p30 treatment.

histology p30 - 1 year.jpg

Figure: Histological image of a chondral defect treated with p30 hydrogel (1 year).

Conclusion

The collected data illustrates the beneficial effect of a new UV-photocrosslinked hyaluronan hydrogel on cartilage repair in vivo in a translational animal model.

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