Tissue Engineering for Total Meniscal Substitution: Animal Study in Sheep Model—Results at 12 Months

Abstract

The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided into three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes, and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At a 12-month gross assessment, histology and histomorphometry were used to assess the meniscus implant, knee joint, and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. The implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those underwent meniscectomy (p<0.0005), and the Osteoarthritis Research Society International score showed that osteoarthritic changes were significantly less in the cell-seeded group than in the meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

Meniscus repair and regeneration: review on current methods and research potential

“…The authors concluded that the hyaluronan-PCL scaffold had a potential for total meniscus regeneration and that the seeding of the scaffold provided some benefits at 4 months follow-up allowing for a larger amount of fibrocartilaginous tissue formation. A following study with 12-month evaluation confirmed the improvement in tissue formation within the tissue engineered menisci, but showed no significant differences in protection from osteoarthritic degeneration between cell-seeded and cell-free scaffolds (Kon et al, 2012). However, both cell-seeded and cell-free implants resulted in better chondroprotection compared to meniscectomised knees.…”

“…Although promising, results of recent experimental studies prompt for new strategies for total meniscus engineering as mere cell seeding does not result typically in an improved outcome and chondroprotection (Kon et al, 2012). In addition, the ideal biomaterial for meniscus tissue engineering has still to be developed.…”

Application of cell and biomaterial-based tissue engineering methods in the treatment of cartilage, menisci and ligament injuries

“…In the TE of the meniscus, HA was used as a scaffold composite together with gelatine [82], collagen [83,84] and PCL [85]. In a rabbit model of meniscus defect, MSCs seeded on hyaluronan/gelatine matrices and implanted to the injury site, integrated well with the host tissue, filled the defect and three months, newly formed fibrocartilage, with hyaline-like cartilage zones, was observed [82].…”

“…The PRP-loaded composite resulted in poor tissue regeneration, while the MSC-seeded scaffold filled the defect with meniscus-like tissue comprising low cell numbers and high type II collagen content. Kon et al [85] investigated hyaluronan/PCL constructs with improved mechanical properties to assess their value as a cell-carrier of autologous chondrocytes. One-year after surgery, cell-seeded scaffolds showed significantly better fibrocartilage formation when compared with the cell-free implants and the group that underwent meniscectomy.…”

Building an Anisotropic Meniscus with Zonal Variations

“…For example, in the ovine model, a hyaluronic-acidpolycaprolactone scaffold with autologous chondrocytes was used to replace the entire meniscus to result in a higher morphological score as compared to total meniscectomy, with signs of integration and vessel ingrowth. 56 The zonal meniscus constructs in this study can similarly be envisioned as full meniscus replacements. It is also possible to trim the zonal meniscus construct into an appropriate implant, as alternatives to partial meniscectomy, to address meniscal tears in either the vascular or avascular zones.…”