Jong Pil Yoon1, Chang-Hwa Lee1, Jae Wook Jung1, Hyun-Joo Lee1, Yong-Soo Lee2, Ja-Yeon Kim2, Ga Young Park3, Jin Hyun Choi3, Seok Won Chung2. 1. Department of Orthopaedic Surgery, Kyungpook National University, School of Medicine, Daegu, Republic of Korea. 2. Department of Orthopaedic Surgery, Konkuk University School of Medicine, Seoul, Republic of Korea. 3. Department of Bio-fibers and Materials Science, College of Agriculture and Life Science, Kyungpook National University, Daegu, Republic of Korea.
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.
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.
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