Massive rotator cuff tears (MRCTs) represent a major clinical concern, especially when degeneration and chronicity are involved, which highly compromise healing capacity. To study the effect of the secretome of mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination of these activated TCs with an electrospun keratin-based scaffold to develop a tissue engineering strategy to improve tendon-bone interface (TBi) healing in a chronic MRCT rat model. Controlled laboratory study. Human TCs (hTCs) cultured with the human MSCs (hMSCs) secretome (as conditioned media [CM]) were combined with keratin electrospun scaffolds and further implanted in a chronic MRCT rat model. Wistar-Han rats (N = 15) were randomly assigned to 1 of 3 groups: untreated lesion (MRCT group, n = 5), lesion treated with a scaffold only (scaffold-only group, n = 5), and lesion treated with a scaffold seeded with hTCs preconditioned with hMSCs-CM (STC_hMSC_CM group, n = 5). After sacrifice, 16 weeks after surgery, the rotator cuff TBi was harvested for histological analysis and biomechanical testing. The hMSCs secretome increased hTCs viability and density in vitro. In vivo, a significant improvement of the tendon maturing score was observed in the STC_hMSC_CM group (mean ± standard error of the mean, 15.6 ± 1.08) compared with the MRCT group (11.0 ± 1.38; P < .05). Biomechanical tests revealed a significant increase in the total elongation to rupture (STC_hMSC_CM, 11.99 ± 3.30 mm; scaffold-only, 9.89 ± 3.47 mm; MRCT, 5.86 ± 3.16 mm; P < .05) as well as a lower stiffness (STC_hMSC_CM, 6.25 ± 1.74 N/mm; scaffold-only, 6.72 ± 1.28 N/mm; MRCT, 11.54 ± 2.99 N/mm; P < .01). The results demonstrated that hMSCs-CM increased hTCs viability and density in vitro. Clear benefits also were observed when these primed cells were integrated into a tissue engineering strategy with an electrospun keratin scaffold, as evidenced by improved histological and biomechanical properties for the STC_hMSC_CM group compared with the MRCT group. This work supports further investigation into the use of MSC secretome for priming TCs toward a more differentiated phenotype, and it promotes the tissue engineering strategy as a promising modality to help improve treatment outcomes for chronic MRCTs.

Massive rotator cuff tears (MRCTs) are usually chronic lesions with pronounced degenerative changes, where advanced fatty degeneration and atrophy can make the tear irreparable. Human mesenchymal stem cells (hMSCs) secrete a range of growth factors and vesicular systems, known as secretome, that mediates regenerative processes in tissues undergoing degeneration. To study the effect of hMSC secretome on muscular degenerative changes and shoulder function on a rat MRCT model. Controlled laboratory study. A bilateral 2-tendon (supraspinatus and infraspinatus) section was performed to create an MRCT in a rat model. Forty-four Wistar-Han rats were randomly assigned to 6 groups: control group (sham surgery), lesion control group (MRCT), and 4 treated-lesion groups according to the site and periodicity of hMSC secretome injection: single local injection, multiple local injections, single systemic injection, and multiple systemic injections. Forelimb function was analyzed with the staircase test. Atrophy and fatty degeneration of the muscle were evaluated at 8 and 16 weeks after injury. A proteomic analysis was conducted to identify the molecules present in the hMSC secretome that can be associated with muscular degeneration prevention. When untreated for 8 weeks, the MRCT rats exhibited a significantly higher fat content (0.73% ± 0.19%) compared with rats treated with a single local injection (0.21% ± 0.04%; P < .01) or multiple systemic injections (0.25% ± 0.10%; P < .05) of hMSC secretome. At 16 weeks after injury, a protective effect of the secretome in the multiple systemic injections (0.62% ± 0.14%; P < .001), single local injection (0.76% ± 0.17%; P < .001), and multiple local injections (1.35% ± 0.21%; P < .05) was observed when compared with the untreated MRCT group (2.51% ± 0.42%). Regarding muscle atrophy, 8 weeks after injury, only the single local injection group (0.0993% ± 0.0036%) presented a significantly higher muscle mass than that of the untreated MRCT group (0.0794% ± 0.0047%; P < .05). Finally, the proteomic analysis revealed the presence of important proteins with muscle regeneration, namely, pigment epithelium-derived factor and follistatin. The study data suggest that hMSC secretome effectively decreases the fatty degeneration and atrophy of the rotator cuff muscles. We describe a new approach for decreasing the characteristic muscle degeneration associated with chronic rotator cuff tears. This strategy is particularly important for patients whose tendon healing after later surgical repair could be compromised by the progressing degenerative changes. In addition, both precise intramuscular local injection and multiple systemic secretome injections have been shown to be promising delivery forms for preventing muscle degeneration.

Background: Lateralized reverse shoulder arthroplasty (RSA) has emerged as an attempt to improve on some of the drawbacks of conventional RSA, such as glenoid notching and decrease in ROM. Although this new design is being used in clinical practice, the evidence is mostly limited to case series and has not been systematically reviewed. Questions/purposes: (1) How much did patient-reported outcome measures (PROMs) and ROM improve among patients who receive a lateralized RSA implant? (2) What proportion of shoulders experience complications, revision surgery, or scapular notching? Methods: The PubMed and EMBASE databases were searched from database inception to January 31, 2020. We included clinical studies that reported the PROMs and/or ROM of patients with insufficient rotator cuffs undergoing RSA with a lateralized implant. All other types of studies and those including patients with fractures, instability or escape, infection, rheumatologic disease, neurologic disease, or revision surgeries as an indication for RSA were excluded. PROMs and ROM were collected and are reported as mean values and ranges. Complications, revision surgery, and scapular notching are presented as proportions. The percentage of the mean change relative to the minimum clinically important difference (MCID) was calculated using the anchor-based value for each outcome. The Methodological Index for Non-randomized Studies (MINORS) was used to assess study quality. The initial search yielded 678 studies; 61 full-text articles were analyzed according to our eligibility criteria. After a detailed analysis, we included nine studies that evaluated 1670 patients (68% of whom [1130] were women) with a mean age of 71.8 ± 0.6 years. The mean follow-up period was 41.1 ± 5.6 months. The mean MINORS score was 12 ± 4. Results: Active ROM improved for forward flexion (mean change 47° to 82°; MCID 12°), abduction (mean change 43° to 80°; MCID 7°), external rotation (mean change 8° to 39°; MCID 3°), and internal rotation (mean change -2 to 1 points). PROM scores also improved, including the American Shoulder and Elbow Surgeons score (mean change 20 to 50; MCID 20.9 points), Constant score (mean change 28 to 40; MCID 5.7 points), Simple Shoulder Test score (mean change 3 to 7; MCID 2.4 points), and VAS score (mean change -1.8 to -4.9; MCID -1.6 points). The proportion of shoulders with complications ranged from 0% (0 of 44) to 21% (30 of 140), and the proportion of shoulders with scapular notching ranged from 0% (0 of 76) to 29% (41 of 140). The proportion of patients undergoing revision ranged from 0% (0 of 44) to 13% (10 of 76) at short-term follow-up. Conclusion: Lateralized RSA is a reasonable alternative to medialized implants for patients with rotator cuff insufficiency because it might reduce the likelihood of scapular notching without apparently compromising PROMs or ROM. More studies are required to determine whether there is a direct correlation between the amount of lateralization and PROMs or ROM.