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.
Highlights
Osteoarthritis is known to be one of the fastest-growing causes of disability worldwide and significantly reduces the quality of life in affected individuals [1]
Animals were kept in indoor runs allowing free movement and unrestricted access to water. ey were fed once a day. e animal experiments were approved by the Animal Experimentation Committee Karlsruhe (G-203/14, G-117/16) and were performed according to the national guidelines for animal care in accordance with European Union Directive (2010/63/EU)
Porcine articular chondrocytes were isolated from healthy porcine knee joints (n 2 donors) from slaughter pigs obtained from the local abattoir as described before [21]
Summary
Osteoarthritis is known to be one of the fastest-growing causes of disability worldwide and significantly reduces the quality of life in affected individuals [1]. Due to an important number of cases where osteoarthritis starts from cartilage injuries or defects in young or middle-aged patients, the effective repair of these defects is a top-priority goal in orthopedic surgery. Many approaches for cartilage repair have been proposed, including microfracture, osteochondral autograft transplantation, mosaicplasty, minced or micronized articular cartilage allografts, autologous matrix-induced chondrogenesis (AMIC), or autologous chondrocyte implantation (ACI) [2]. None of these methods have been able to generate functional hyaline joint cartilage but rather induce fibrocartilage with inferior mechanical properties [2]. Especially for AMIC and ACI procedures, is the fixation of the constructs within the defect and to the adjacent native cartilage
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