Osteochondral Repair by a Novel Interconnecting Collagen–Hydroxyapatite Substitute: A Large-Animal Study

Abstract

A novel three-dimensional bicomponent substitute made of collagen type I and hydroxyapatite was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase. Thirty-six osteochondral lesions were created in the trochlea of six pigs; in each pig, two lesions were treated with scaffolds seeded with autologous chondrocytes (cell+group), two lesions were treated with unseeded scaffolds (cell- group), and the two remaining lesions were left untreated (untreated group). After 3 months, the animals were sacrificed and the newly formed tissue was analyzed to evaluate the degree of maturation. The International Cartilage Repair Society (ICRS) macroscopic assessment showed significantly higher scores in the cell- and untreated groups when compared with the cell+ group. Histological evaluation showed the presence of repaired tissue, with fibroblast-like and hyaline-like areas in all groups; however, with respect to the other groups, the cell- group showed significantly higher values in the ICRS II histological scores for "cell morphology" and for the "surface/superficial assessment." While the scaffold seeded with autologous chondrocytes promoted the formation of a reparative tissue with high cellularity but low glycosaminoglycans (GAG) production, on the contrary, the reparative tissue observed with the unseeded scaffold presented lower cellularity but higher and uniform GAG distribution. Finally, in the lesions treated with scaffolds, the immunohistochemical analysis showed the presence of collagen type II in the peripheral part of the defect, indicating tissue maturation due to the migration of local cells from the surroundings. This study showed that the novel osteochondral scaffold was easy to handle for surgical implantation and was stable within the site of lesion; at the end of the experimental time, all implants were well integrated with the surrounding tissue and no signs of synovitis were observed. The quality of the reparative tissue seemed to be superior for the lesions treated with the unseeded scaffolds, indicating the promising potential of this novel biomaterial for use in a one-stage procedure for osteochondral repair.

Selective laser sintering scaffold with hierarchical architecture and gradient composition for osteochondral repair in rabbits

“…1). Moreover, instead of traditional techniques [17, 43, 44], SLS was employed for the fabrication of scaffolds due to its innate advantages in the rapid manufacturing of lamellar structure, the precise control of sophisticated design, and the potential for mass production. The application of SLS technique creatively overcomes the drawbacks of traditional methods, including restrictions on layer number, limited control of hierarchical structure, unexpected separation between the layers, and poor connective porosity.…”

Recent Strategies in Osteochondral Substitutes Design: Towards the Mimicking of a Multifaceted Anatomical Unit from the Nano to the Macro Level

“…As another example, a novel 3D bicomponent substitute made of type I collagen and HA was developed [27,41] and tested for the repair of osteochondral lesions in a swine model [42]. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the chondral and the osseous phase (Figure 2d).…”

Perspectives on Animal Models Utilized for the Research and Development of Regenerative Therapies for Articular Cartilage

“…Pig models for partial-or full-thickness cartilage defects were also used in several studies [55]. Thicker cartilage (1.5-2.0 mm) [56], up-right (instead of squatting) knee, and larger joint sizes are advantages of the porcine cartilage defect model.…”

“…Thicker cartilage (1.5-2.0 mm) [56], up-right (instead of squatting) knee, and larger joint sizes are advantages of the porcine cartilage defect model. Nevertheless, pigs are characterized by difficult handling, large size, requirements in housing, and aggressive demeanor, while mini-pigs could offset some of these shortcomings [55]. It is critical to use mature mini-pigs to diminish the influence of spontaneous cartilage repair, as immature minipig cartilage (less than 42-52 weeks) has a relatively high spontaneous healing capacity [57].…”