Novel engineered tendon-fibrocartilage-bone composite with cyclic tension for rotator cuff repair

Abstract

Surgical repair of rotator cuff tears presents a significant clinical challenge with high failure rates and inferior functional outcomes. Graft augmentation improves repair outcomes; however, currently available grafting materials have limitations. Although cell-seeded decellularized tendon slices may facilitate cell infiltration, promote tendon incorporation, and preserve original mechanical strength, the unique fibrocartilage zone is yet to be successfully reestablished. In this study, we investigated the biological and mechanical properties of an engineered tendon-fibrocartilage-bone composite (TFBC) with cyclic tension (3% strain; 0.2 Hz). Decellularized TFBCs seeded with bone marrow-derived mesenchymal stem cell (BMSCs) sheets and subjected to mechanical stimulation for up to 7 days were characterised by histology, immunohistochemistry, scanning electron microscopy, mechanical testing, and transcriptional regulation. The decellularized TFBC maintained native enthesis structure and properties. Mechanically stimulated TFBC-BMSC constructs displayed increased cell migration after 7 days of culture compared with static groups. The seeded cell sheet not only integrated well with tendon scaffold but also distributed homogeneously and aligned to the direction of stretch under dynamic culture. Developmental genes were regulated including scleraxis, which was significantly upregulated with mechanical stimulation. The Young's modulus of the cell-seeded constructs was significantly higher compared with the noncell-seeded controls. In conclusion, the results of this study reveal that the TFBC-BMSC composite provides an ideal multilayer construct for cell seeding and growth, with mechanical preconditioning further enhances cell penetration and differentiation. The BMSC cell sheet revitalised TFBC in conjunction with mechanical stimulation could serve as a novel and primed biological patch to improve rotator cuff repair.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…bone marrow-derived MSC sheets under cyclic tension for 7 days [55]. Mechanical tension led to increased cell migration and aligned distribution of cells within the scaffold, resulting in the upregulation of tenogenic genes as scleraxis [55].…”

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels

“…Failure is ascribed to a lack of functional enthesis structure, consisting of tendon, non-calcified fibrocartilage, calcified fibrocartilage, and bone, and formation of fibrovascular scar tissue with inferior mechanical properties 4 . Various tissue engineering strategies have been developed to promote tendon-to-bone healing and have demonstrated potential for functional re-integration of the injured rotator cuff 5 - 8 . However, it remains challenging to acquire functional regeneration of native enthesis at the tendon-to-bone interface.…”

Biomechanical Comparison of Augmentation of Engineered Tendon-Fibrocartilage-Bone Composite With Acellular Dermal Graft Using Double Rip-Stop Technique for Canine Rotator Cuff Repair

“…TFBCs (n = 10) were prepared based on previously established procedures. 16 , 24 , 25 Briefly, patellar tendons were transected near the distal patellar bone. The tibial tubercles with the intact patellar tendon–tibial bony attachments were cut carefully with a bone saw ( Figure 1A ).…”

“…Leung et al 23 reported that the BTI between homogeneous tissues (tendon-tendon and bone-bone healing) had better healing quality than the healing between heterogeneous tissues (bone-tendon healing). Recently, a novel engineered tendon-fibrocartilage-bone composite (TFBC) for rotator cuff repair has been developed 16 , 24 that preserves the natural fibrocartilage zone, replacing difficult BTI healing with similar tissue healing interfaces (tendon-tendon and bone-bone). An in vivo study confirmed that TFBC enhanced rotator cuff healing by preserving the fibrocartilage zone.…”