Sustained Delivery of Transforming Growth Factor β1 by Use of Absorbable Alginate Scaffold Enhances Rotator Cuff Healing in a Rabbit Model

Abstract

Background: The failure rate for healing after rotator cuff repair is relatively high. Purpose: To establish a system for sustained release of transforming growth factor β1 (TGF-β1) using an alginate scaffold and evaluate the effects of the sustained release of TGF-β1 on rotator cuff healing in a rabbit model. Study Design: Controlled laboratory study. Methods: Before the in vivo animal study, a standard MTS assay was performed to evaluate cell proliferation and metabolic activity on the alginate scaffold. Additionally, an enzyme-linked immunosorbent assay was performed to confirm the capacity of the sustained release of TGF-β1-containing alginate scaffold. Once the in vitro studies were completed, bilateral supraspinatus tendon repairs were performed in 48 rabbits that were allocated to 3 groups (n = 16 each) (group 1, supraspinatus repair only; group 2, supraspinatus repair with TGF-β1 single injection; group 3, supraspinatus repair with TGF-β1 sustained release via an alginate-based delivery system). Biomechanical and histological analyses were performed to evaluate the quality of tendon-to-bone healing at 12 weeks after rotator cuff repair. Results: The cell proliferation rate of the alginate scaffold was 122.30% compared with the control (fresh medium) group, which confirmed that the alginate sheet had no cytotoxicity and enhanced cell proliferation. Additionally, the level of TGF-β1 was found to increase with time on the alginate scaffold. Biomechanically, group 3 exhibited a significantly heightened ultimate failure load compared with groups 1 and 2 (group 1, 74.89 ± 29.82 N; group 2, 80.02 ± 34.42 N; group 3, 108.32 ± 32.48 N; P = .011) and more prevalent midsubstance tear compared with group 1 ( P = .028). However, no statistical differences were found in the cross-sectional area of the supraspinatus tendon (group 1, 32.74 ± 9.38; group 2, 33.76 ± 8.89; group 3, 34.80 ± 14.52; P = .882) and ultimate stress (group 1, 2.62 ± 1.13 MPa; group 2, 2.99 ± 1.81 MPa; group 3, 3.62 ± 2.24 MPa; P = .317). Histologically, group 3 exhibited a significantly heightened modified total Bonar score (group 1, 5.00 ± 1.54; group 2, 6.12 ± 1.85; group 3, 7.50 ± 1.31; P = .001). In addition, the tendon-to-bone interface for group 3 demonstrated better collagen orientation, continuity, and organization, and the area of new fibrocartilage formation was more evident in group 3. Conclusion: At 12 weeks after rotator cuff repair, the authors found improved biomechanical and histological outcomes for sustained release of TGF-β1 using alginate scaffold in a rabbit model. Clinical Relevance: The alginate-bound growth factor delivery system might improve healing after rotator cuff repair in humans.