Mechanically Preconditioned Biomimetic Gradient Scaffold for Tendon-to-Bone Regeneration in a Rabbit Rotator Cuff...

Healing of the tendon-bone interface (TBI) after rotator cuff injury is limited, often leading to scar-mediated repair. Decellularized tendon fibrocartilage-bone composite (dTFBC) and bone marrow mesenchymal stem cell sheets (BMSCS) improve repair in preclinical models, but full scaffold encapsulation with mechanical preconditioning remains unexplored.

To evaluate TBI regeneration using mechanically preconditioned, BMSCS-encapsulated dTFBC scaffolds in a rabbit model.

Controlled laboratory study.

A total of 48 male New Zealand White rabbits were randomized into 4 groups (n = 12 each): (1) standard repair (control); (2) repair with dTFBC; (3) repair with dTFBC-BMSCS; and (4) repair with mechanically preconditioned dTFBC-BMSCS (mdTFBC-BMSCS). Healing at 12 weeks was assessed via gross observation, histomorphological and immunohistochemical analyses, and biomechanical testing.

The mdTFBC-BMSCS group demonstrated a higher ultimate failure load (mean, 203.9 ± 65.6 N) than both the control (118 ± 37.4 N; P = .003) and dTFBC groups (127 ± 44.1 N; P = .008), with no significant difference between the 2 BMSCS-treated groups. Histological analysis revealed enhanced fibrocartilage formation, improved collagen fiber organization, and reduced inflammation infiltration at the TBI in the mdTFBC-BMSCS group. Immunohistochemical analysis showed greater collagen type 2 alpha 1 chain-, interleukin 10-, and arginase 1-positive areas in the mdTFBC-BMSCS group than in the control and dTFBC groups.

Mechanically preconditioned, fully BMSCS-encapsulated dTFBC scaffolds promoted TBI regeneration, with enhanced cellular integration, fibrocartilage formation, and favorable biomechanical performance.

This biomimetic scaffold strategy may enhance biological healing and reduce the risk of retear after rotator cuff repair.