Engineering Tendon With a Novel Composite Scaffold and Repairing Monkey Tendon Defect

Abstract

Objective: The use of biodegradable materials as scaffold is essential for tendon engineering to repair tendon defects. However, poor mechanical property of in vitro engineered tendon is a major challenge for clinical application. This study aims to develop a composite scaffold by combining different types of polymer fibers with knitted technique and to test the long-term result of the engineered tendon using this new designed composite scaffold for repairing the monkey tendon defect. Materials and Methods: Four groups of knitted scaffolds were first prepared with different ratio of polyglycolide acid (PGA) to polylactic acid (PLA): (1) 100% PGA; (2) PGA/PLA, 4:2; (3) PGA/PLA, 2:4; and (4) 100% PLA, respectively. The hydrolysis and biocompatibility of these scaffolds were tested. Then by using these scaffolds, the in vitro engineered tendon with human dermal fibroblasts and in vivo monkey tendon defect repair were investigated. Results: The hydrolysis assay showed that group 1 scaffold degraded fastest with a significant mass loss and tensile strength decrease. Increase of PLA content led to a decrease of the mass loss rate and resulted in an enhancement of tensile strength. The PGA/PLA, 4:2, scaffold maintained about 40% (62.9 ± 5.5 N) of its initial tensile strength after 4 weeks of hydrolysis and about 31% (48.9 ± 2.9 N) after 20 weeks, indicating a proper strength for implantation. The cell-scaffold biocompatibility assay revealed good cell survival and extracelular matrix (ECM) production in groups 1 and 2. At the same time, the in vitro tendon engineering with human dermal fibroblasts showed that only groups 1 and 2 formed tendon-like tissues while not in the other two groups. At 8 weeks, the failure load of engineered tendon in group 2 reached to 55.3 ± 5.2 N, a sufficient strength for in vivo implantation. Furthermore, in in vivo monkey tendon defect repairing model using the PGA/PLA, 4:2 scaffold, the repaired flexor digitorum profundus (FDP) and Achilles tendon exhibited shiny-white color and cord-like shape with a relatively smooth surface and without obvious material residue 2 years postrepair. A relatively mature tissue structure and the D-band periodicity were clearly developed. There was no significant difference in maximal load between the engineered Achilles tendon (233.7 ± 33.3 N) and the normal Achilles tendon (249.4 ± 35.2 N; P > .05). The repaired finger exhibited normal passive flexion and extension motion and participated in grasping. Conclusions: This study designed a novel degradable composite scaffold for tendon engineering, which could withstand the mechanical stretch instantly after in vivo implantation. The PGA/PLA, 4:2 composite scaffold was considered the most ideal scaffold. The long-term results for repairing the defects of flexor digitorum superficialis (FDS) and Achilles tendon in a Rhesus monkey model were encouraging, which may give insight into future clinical translation of tendon engineering.