Table 1.
Clinical (Human) Studies with a Minimum of Level 3 Evidence (Cohort Studies) Examining the Benefit of Scaffolds, Augmentation at the Healing Tendon–Bone Interface, or a Combination of the Two
| Augmentation strategy | Study | Level of evidence | Tear size | Exclusion of tears with fatty infiltration? | Sample size | Follow-up period (range) | Failure rate on US/MRI | Functional outcome | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| Scaffold (porcine SIS) | Iannotti et al.42 | 2 (RCT) | Large and massive (>4 cm) | No | CG: 15 | 12 months (12–26.5) | CG: 6/15 | No difference between groups using PENN | AG: 3/15 postoperative inflammatory reaction |
| AG: 15 | AG: 11/15 | ||||||||
| Scaffold (porcine SIS) | Walton et al.43 | 3 (case–control) | — | No | CG: 16 | 24 months | CG: 7/12 | AG had significantly less strength in internal rotation and adduction than CG | AG: 4/10 postoperative inflammatory reaction |
| AG: 15 | AG: 6/10 | ||||||||
| Scaffold (human dermal) | Barber et al.44 | 2 (RCT) | Large two-tendon tears (>3 cm) | No | CG: 20 | 24 months (12–38) | CG: 9/15 | AG had significantly better ASES and constant score | None |
| AG: 22 | AG: 3/20 | ||||||||
| Scaffold (polypropylene or bovine collagen) | Ciampi et al.46 | 3 (Cohort) | Full thickness, two-tendon tear with <2 cm postoperative residual retraction | Yes, advanced fatty infiltration | CG: 51 | 36 months | CG: 21/51 | UCLA scores were significantly higher for the polypropylene group; Elevation and strength of the polypropylene group were significantly higher than other groups | None |
| Collagen: 49 | Collagen: 25/49 | ||||||||
| Polypropylene: 52 | Polypropylene: 9/52 | ||||||||
| Scaffold (fascia lata autograft) | Mori et al.77 | 3 (Cohort) | Massive rotator cuff tears | No | LG: 26 | 24 months | LG: 7/26 | Constant score and ASES were significantly higher in low-grade group compared to high-grade group | None |
| HG: 19 | HG: 17/19 | ||||||||
| Enthesis (microfracture) | Osti etal.245 | 2 (RCT) | — | Yes, severe fatty infiltration | CG: 29 | 24 months (24–53) | CG: 3/29 | At 3 months, UCLA, VAS, and constant scores better in the microfracture group. No difference at 2 years | None |
| MG: 28 | MG: 2/26 | ||||||||
| Enthesis (microfracture) | Milano et al.246 | 2 (RCT) | Full thickness | No | CG: 38 | 24 months (25–31) | CG: 18/38 | No significant difference in DASH score. Large tear had significantly greater healing with microfracture | None |
| MG: 35 | MG: 12/35 | ||||||||
| Enthesis (MSCs) | Hernigou et al.170 | 3 (Case–control) | Tear <3 cm | No | CG: 45 | 10 years | CG: 35/45 | Number of MSCs correlated with grade of healing. Total MSCs >2500/mL had more healing and less failure than when MSCs <1500/mL. | None |
| MSCG: 45 | MSCG: 6/45 | ||||||||
| Scaffold (human dermis) and enthesis (microfracture) | Yoon et al.225 | 3 (Cohort) | Massive rotator cuff tear | No | CG: 54 | 24 months (14–53) | CG: 25/54 | No difference in VAS, constant, and ASES score | None |
| MPG: 21 | MPG: 4/21 |
No clinical studies investigating cell or pharmaceutical strategies for reversing muscle degeneration were identified. Reviews of preclinical studies are not included here, but have focused on scaffold augmentation,31,57 tendon-bone healing,109,235 and muscle regeneration.198
AG, augmented group; CG, control group; HG, high grade degeneration of both infraspinatus and supraspinatus; LG, low grade fatty degeneration of infraspinatus but high grade degeneration supraspinatus; MG, microfracture group; MPG, marrow stimulation and patch group; MRI, magnetic imaging resonance; MSC, mesenchymal stem cell; MSCG, mesenchymal stem cell group; PENN, PENN shoulder score; RCT, randomized controlled trial; SIS, small intestine submucosa; UCLA, University of California at Los Angeles score; US, ultrasound; VAS, visual analog scale.