Background: Rotator cuff regeneration using tissue engineering techniques is a challenging treatment in elderly patients with irreparable rotator cuff tears. Hypothesis: A polyglycolic acid sheet scaffold with seeded mesenchymal stem cells (MSCs) may enhance the expression of type I collagen products and increase the mechanical strength of the regenerated tendon in vivo. Study Design: Controlled laboratory study. Methods: A surgically created defect of infraspinatus tendons of rabbits was reconstructed with 2 different materials, a polyglycolic acid (PGA) sheet alone (PGA group) (n = 34) and a PGA sheet seeded with autologously cultured MSCs (MSC group) (n = 34). The authors created a tendon defect model without embedding any graft as the control model (control group) (n = 34). The rabbits were sacrificed at 4, 8, and 16 weeks after the operation and then were histologically evaluated. The rabbits were also biomechanically evaluated by measuring the ultimate failure loads and Young’s modulus at 4 and 16 weeks following implantation. Results: In the MSC group, the fibrocartilage layers and Sharpey fibers were found regularly in the insertion site at 8 weeks compared with the PGA group. In control group, thin membranes with many fibroblasts arranged in an irregular pattern linked the end of the torn cuff to the bone without any Sharpey fibers and type I collagen. A large volume of type I collagen was found in comparison with type III collagen at 16 weeks in the MSC group, whereas type III collagen was more prevalent than type I in the PGA group. The tendon maturing score in the MSC group had higher values than the PGA and control groups at 8 and 16 weeks (mean values were 21.0 ± 0.89, 24.0 ± 2.53 in the MSC group; 16.7 ± 2.25, 21.3 ± 2.42 in the PGA group; and 10.2 ± 0.98, 12.2 ± 1.72 in the control group, respectively) ( P < .05). The results of the mechanical analysis revealed that the regenerated tendons in the MSC group had better tensile strength than in the PGA and control groups at 16 weeks (mean values were 3.04 ± 0.54 in the MSC group, 2.38 ± 0.63 in the PGA group, and 1.58 ± 0.13 in the control group) ( P < .05). Conclusion: Bone marrow–derived MSCs were able to regenerate tendon-bone insertions and the tendon belly, including the production of type I collagen, and increased the mechanical strength of the regenerated rotator cuff tendon. Clinical Relevance: Rotator cuff regeneration using MSCs is a promising treatment for massive rotator cuff defects.

The ideal scaffold for tendon engineering would possess the basic structure of the tendon, native extracellular matrix, and capability of cell seeding. The purpose of this study was to assess the tissue engineering potential of a novel composite consisting of a decellularized multilayer sliced tendon (MST) scaffold seeded with bone marrow stromal cells (BMSC). BMSC and infraspinatus tendons were harvested from 20 dogs. The tendons were sectioned in longitudinal slices with a thickness of 50 µm. The slices were decellularized, seeded with BMSC, and then bundled into one composite. The composite was incubated in culture media for 14 days. The resulting BMSC-seeded MST was evaluated by qRT-PCR and histology. The BMSC viability was assessed by a fluorescent tracking marker. Histology showed that the seeded cells aligned between the collagen fibers of the tendon slices. Analysis by qRT-PCR showed higher tenomodulin and MMP13 expression and lower collagen type I expression in the composite than in the BMSC before seeding. BMSC labeled with fluorescent tracking marker were observed in the composite after culture. Mechanical testing showed no differences between scaffolds with or without BMSC. BMSC can survive in a MST scaffold. The increased tenomodulin expression suggests that BMSC might express a tendon phenotype in this environment. This new composite might be useful as a model of tendon tissue engineering.

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The purpose of this study was to investigate an engineered composite of multilayer acellular tendon slices seeded with bone marrow stromal cells (BMSCs) as a possible solution for tendon reconstruction. BMSCs were harvested from 15 rabbits and infraspinatus tendons were harvested from 17 dogs. The decellularized tendons were sectioned in longitudinal slices with a thickness of 50 μm. The BMSCs were seeded on the slices and then the slices were bundled into one composite. The composite was implanted into a rabbit patellar tendon defect. Tendon slices without BMSCs were implanted into the contralateral patellar tendon as a control. The composites were evaluated by histology and qRT–PCR. The viability of BMSCs was assessed using a fluorescent marker. Histology showed viable cells between the collagen fibres on the cell-seeded side. Analysis by qRT–PCR showed higher tenomodulin, collagen type III, MMP3 and MMP13 expressions and lower collagen type I expression in the cell-seeded composite than in the tendon slices without BMSCs. We conclude that BMSCs can survive in a multilayer composite, express a tendon phenotype and enhance the metabolism of tendon in vivo. This in vivo study suggests a potential utility of this composite in tendon reconstruction.

The purpose of this study was to evaluate histologically and biomechanically the interface between porous hydroxyapatite ceramics and a tendon grafted into ceramics, and to compare the interface in two ceramics with different porous structures: interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with an effective porosity index (interpore diameter > 20 microm) of 63.6%, and porous calcium hydroxyapatite ceramics with less interconnection (HA-L) with an effective porosity index of 5.5%. The tendon-IP-CHA complex and the tendon-HA-L complex were implanted into the bone defects made in both knees of rabbits. With IP-CHA, abundant fibrous tissue, including vessels and collagen fiber continuity, was observed inside interface-region pores. The amount of osseous tissue in interface-region pores increased over time, and at 24 weeks after operation, the tendon was in direct contact with the osseous tissue in IP-CHA. With HA-L, the amount of fibrous tissue in interface-region pores was low and did not increase. The results of biomechanical analysis revealed that the maximum tendon pull-out load from IP-CHA was significantly higher than that from HA-L. With the porous hydroxyapatite ceramics having highly interconnecting porous structure, a bioactive interface was achieved between ceramics and grafted tendon. On the basis of these results, we conclude that bone defects, including tendon insertion, can be reconstructed using IP-CHA.