Development of a Tissue-Engineered Artificial Ligament: Reconstruction of Injured Rabbit Medial Collateral Ligament With Elastin-Collagen and Ligament Cell Composite Artificial Ligament

组织工程人工韧带的开发:用弹性蛋白-胶原蛋白和韧带细胞复合人工韧带重建损伤的兔内侧副韧带

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作者:Masaki Hirukawa, Shingo Katayama, Tatsuya Sato, Kota Inoue, Kosuke Niwa, Naoya Ito, Tetsuya Hattori, Takashi Hosoi, Hironori Unno, Yoshiaki Suzuki, Masahiro Hasegawa, Keiichi Miyamoto, Takashi Horiuchi

Abstract

Ligament reconstruction using a tissue-engineered artificial ligament (TEAL) requires regeneration of the ligament-bone junction such that fixation devices such as screws and end buttons do not have to be used. The objective of this study was to develop a TEAL consisting of elastin-coated polydioxanone (PDS) sutures covered with elastin and collagen fibers preseeded with ligament cells. In a pilot study, a ring-type PDS suture with a 2.5 mm (width) bone insertion was constructed with/without elastin coating (Ela-coat and Non-coat) and implanted into two bone tunnels, diameter 2.4 mm, in the rabbit tibia (6 cases each) to access the effect of elastin on the bond strength. PDS specimens taken together with the tibia at 6 weeks after implantation indicated growth of bone-like hard tissues around bone tunnels accompanied with narrowing of the tunnels in the Ela-coat group and not in the Non-coat group. The drawout load of the Ela-coat group was significantly higher (28.0 ± 15.1 N, n = 4) than that of the Non-coat group (7.6 ± 4.6 N, n = 5). These data can improve the mechanical bulk property of TEAL through extracellular matrix formation. To achieve this TEAL model, 4.5 × 106 ligament cells were seeded on elastin and collagen fibers (2.5 cm × 2.5 cm × 80 µm) prior to coil formation around the elastin-coated PDS core sutures having ball-shape ends with a diameter of 2.5 mm. Cell-seeded and cell-free TEALs were implanted across the femur and the tibia through bone tunnels with a diameter of 2.4 mm (6 cases each). There was no incidence of TEAL being pulled in 6 weeks. Regardless of the remarkable degradation of PDS observed in the cell-seeded group, both the elastic modulus and breaking load of the cell-seeded group (n = 3) were comparable to those of the sham-operation group (n = 8) (elastic modulus: 15.4 ± 1.3 MPa and 18.5 ± 5.7 MPa; breaking load: 73.0 ± 23.4 N and 104.8 ± 21.8 N, respectively) and higher than those of the cell-free group (n = 5) (elastic modulus: 5.7 ± 3.6 MPa; breaking load: 48.1 ± 11.3 N) accompanied with narrowed bone tunnels and cartilage matrix formation. These data suggest that elastin increased the bond strength of TEAL and bone. Furthermore, our newly developed TEAL from elastin, collagen, and ligament cells maintained the strength of the TEAL even if PDS was degraded.

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