Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model

Abstract

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

Development of a 3D-printed bioabsorbable composite scaffold with mechanical properties suitable for treating large, load-bearingarticular cartilage defects

“…While it is common for engineered cartilage tissue constructs to be assessed for their compressive modulus, less often reported, and a strength of this study, was the investigation of compatible fixation of biomimetic ECM constructs within a large load-bearing cartilage defect (Marchiori et al, 2019). A comparison of chondral biomaterial fixation techniques in largeanimal models by Lotz et al (2021) found that many hydrogels show promise in vitro but fail in vivo due to inadequate fixation within a chondral defect. These data further justify the importance of incorporating a viable fixation strategy early in articular-cartilage biomaterial development.…”

“…Maintaining the favourable porous structure under physiological loads is essential to support proper cellular infiltration (Matsiko et al, 2014). Unlike focal chondral defects, large-area chondral defects experience greater lateral frictional forces, increasing the risk of delamination of prochondrogenic biomaterials from chondral defects (Lotz et al, 2021). Therefore, proper biomaterial fixation within a large-area chondral defect is essential to prevent delamination and promote adequate cellular infiltration for successful tissue integration (Nehrer et al, 1998).…”

Biocompatible Hydrogel for Intra-Articular Implantation Comprising Cationic and Anionic Polymers of Natural Origin: In Vivo Evaluation in a Rabbit Model

“…The recommended management of the symptomatology of knee OA consists of conservative, non-pharmacological strategies in the first instance, then the use of pharmacological therapies, and, as a last resort, surgical options [1][2][3]. The injection of viscosupplementation substances is an option prior to surgery [4]. Regarding viscosupplementation, the main compound used currently is hyaluronic acid (HA), which is presented in different formulations [5,6].…”