Bioactive Scaffold With Spatially Embedded Growth Factors Promotes Bone-to-Tendon Interface Healing of Chronic Rotator Cuff Tear in Rabbit Model

Abstract

Background: Functional restoration of the bone-to-tendon interface (BTI) after rotator cuff repair is a challenge. Therefore, numerous biocompatible biomaterials for promoting BTI healing have been investigated. Purpose: To determine the efficacy of scaffolds with spatiotemporal delivery of growth factors (GFs) to accelerate BTI healing after rotator cuff repair. Study Design: Controlled laboratory study. Methods: An advanced 3-dimensional printing technique was used to fabricate bioactive scaffolds with spatiotemporal delivery of multiple GFs targeting the tendon, fibrocartilage, and bone regions. In total, 50 rabbits were used: 2 nonoperated controls and 48 rabbits with induced chronic rotator cuff tears (RCTs). The animals with RCTs were divided into 3 groups: (A) saline injection, (B) scaffold without GF, and (C) scaffold with GF. To induce chronic models, RCTs were left unrepaired for 6 weeks; then, surgical repairs with or without bioactive scaffolds were performed. For groups B and C, each scaffold was implanted between the bony footprint and the supraspinatus tendon. Four weeks after repair, quantitative real-time polymerase chain reaction and immunofluorescence analyses were performed to evaluate early signs of regenerative healing. Histological, biomechanical, and micro–computed tomography analyses were performed 12 weeks after repair. Results: Group C had the highest mRNA expression of collagen type I alpha 1, collagen type III alpha 1, and aggrecan. Immunofluorescence analysis showed the formation of an aggrecan+/collagen II+ fibrocartilaginous matrix at the BTI when repaired with scaffold with GFs. Histologic analysis revealed greater collagen fiber continuity, denser collagen fibers, and a more mature tendon-to-bone junction in GF-embedded scaffolds than those in the other groups. Group C demonstrated the highest load-to-failure ratio, and modulus mapping showed that the distribution of the micromechanical properties of the BTI repaired with GF-embedded scaffolds was comparable with that of the native BTI. Micro–computed tomography analysis identified the highest bone mineral density and bone volume/total volume ratio in group C. Conclusion: Bioactive scaffolds with spatially embedded GFs have significant potential to promote the BTI healing of chronic RCTs in a rabbit model. Clinical Relevance: The scaffolds with spatiotemporal delivery of GF may serve as an off-the-shelf biomaterial graft to promote the healing of RCTs.

Understanding Fibrous Tissue in the Effective Healing of Rotator Cuff Injury

“…In terms of cell sources, researchers have explored various options for tissue engineering scaffolds in rotator cuff tendon tears. These include tenocytes [ 134 , 135 ], fibroblast [ 136 , 137 ] and stem cells [ 80 , 89 , 138 , 139 ]. The selected cell source should have the potential to differentiate into tenocytes, which are the main cells responsible for tendon regeneration.…”