Abstract
BackgroundArticular cartilage defects are limited to their regenerative potential in human adults. Our current study evaluates tissue regeneration in a surgically induced empty defect site with hyaluronan thiomer as a provisional scaffold in a gel/matrix combination without cells on rabbit models to restore tissue formation.MethodsAn osteochondral defect of 4 mm in diameter and 5 mm in depth was induced by mechanical drilling in the femoral center of the trochlea in 18 New Zealand White rabbits. Previously evaluated from an in vitro study hyaluronan thiomer matrix, and a hyaluronan thiomer gel was used to treat the defect. As a control, the defect was left untreated. During the whole study, rabbits were clinically examined and after 4 (n = 3) or 12 (n = 3) weeks, the rabbits were sacrificed. Joints were evaluated macroscopically (Brittberg score) and by histology (O’Driscoll score). Synovial cells from the synovial fluid smear were histopathologically evaluated.ResultsThe healing of the defects varied intra-group wise at the first observation period. After 12 weeks the results concerning the cartilage repair score were inhomogeneous within each group, while the macroscopic analysis was more homogenous. In the synovial fluid smear, the mean score of infiltrated synovial and non-synovial cells was slightly increased after 4 weeks and slightly decreased after 12 weeks in both the treatment groups in comparison to the untreated control.ConclusionsTaken together with results from the in vivo study indicated that implantation of hyaluronan thiomer as a combination of gel and matrix might enhance articular cartilage regeneration in an empty defect. Despite their benefits, the intrinsic healing capacity of New Zealand rabbits is a limitation for comparative test subject in pre-clinical models of cartilage defects.
Highlights
Articular cartilage defects are limited to their regenerative potential in human adults
HA-based biomaterials are advantageous with biological properties that can bind to chondrocytes (Bauer et al 2015) or mesenchymal stem cells (MSC’s) through the CD44 cell surface receptor (Jakobsen et al 2010) and direct chondrogenic marker genes responsible for extracellular matrix production
In 4 animals treated with 1.75% hyaluronan thiomer gel (HA gel), an increased incidence of swelling was noted at the surgery site only at some time points and in some animals with an increased body temperature (39.5 °C) and reduced food consumption
Summary
Articular cartilage defects are limited to their regenerative potential in human adults. Our current study evaluates tissue regeneration in a surgically induced empty defect site with hyaluronan thiomer as a provisional scaffold in a gel/matrix combination without cells on rabbit models to restore tissue formation. Many different biomaterials are under experimental investigation or are already used in clinical applications (Cook et al 2016). These biomaterials are composed of natural polymers like collagen (Gille et al 2010; Pascarella et al 2010), agarose (Wang et al 2011), hyaluronan (Solchaga et al 2000; Kang et al 2009), Bauer et al Journal of Experimental Orthopaedics (2017) 4:14. HA scaffold investigated for one-stage cartilage repair combined with autologous bone marrow concentrates had superior clinical outcomes independent of the patient’s age or defect size post follow-up at 5 years (Gobbi and Whyte 2016)
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