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.