Summary Statement

A resorbable and biocompatible polymer-based scaffold was used for the proliferation and delivery of adipose derived stromal cells, as well as delivery of a cell growth/differentiation promoting factor for improved tendon defect regeneration.

Introduction and Aims: There are more than 200,000 anterior cruciate ligament (ACL) ruptures each year in the United States. The replacements used for ACL repair do not fully recreate the ACL’s function and histological appearance. Therefore, a novel tissue-engineered ligament was designed and evaluated after ACL reconstruction in a rabbit model.

Method: Rabbits received tissue-engineered ligaments or tissue-engineered ligaments seeded with primary rabbit ACL cells. The tissue-engineered ligaments were composed of multifilament poly-L-lactide yarn (70 denier) fabricated into novel 24 yarn 3-D braids. Scaffolds were designed to be easily handled and fixed by the surgeon in ACL reconstructions using the suture over the button technique. A continuous scaffold design accommodated the flexibility of intra-articular loads and the rigours of the bone tunnels. The contralateral legs were used as controls. A key parameter for tissue ingrowth was scaffold porosity at 58 ± 9% and mode pore diameter of 183 ± 83 μm.

Results: Histological evaluations showed slow collagen tissue infiltration at the surface of the replacement at the four-week time point for both the tissue-engineered ligament and cell-seeded tissue-engineered ligament. At the 12-week time point, both replacements showed collagen ingrowth and remodelling across the entire implant occurred with a thin fibrous capsule. The cell-seeded tissue-engineered ligament demonstrated greater levels of mature collagen ingrowth and healing compared to the non-cell seeded tissue-engineered ligament. The initial tensile strength properties of the scaffold were 332 ± 20 N and 354 ± 68 MPa, which compared well to the rabbit ACL control (314 ± 66 N). The tensile properties of the tissue-engineered ligament and seeded tissue-engineered ligament at four weeks were 67% and 76%, respectively of control. The tensile properties of the biodegradable implant decreased with time for the tissue-engineered and cell seeded tissue-engineered ligament and by 12 weeks was 9% and 30% respectively, as compared to the rabbit ACL control. The 30% strength retention for the tissue-engineered ligament replacements at 12 weeks was greater than reported by others using poly(lactic acid) and polypropylene ligament augmentation devices (LAD) at 12 weeks, with values of 13% and 16% of control strength retention, respectively.

Conclusion: The results of this study demonstrate the promise of a novel cell seeded tissue-engineered ligament for anterior cruciate ligament regeneration.