Mercuri, Jeremy

Purpose To evaluate the effects of this graft preparation technique on histologic evidence of tenocyte mechanical damage. Methods A consecutive series of patients undergoing biceps tenodesis for shoulder pathology were evaluated. After suprapectoral tenodesis, 27 mm of the long head of the biceps was secured for compression into the patch. The remaining length of the residual tendon was longitudinally split, resulting in 2 equal lengths of remnant tendon from the same zone. One sample was sent to pathology with no preparation, and the other was prepared as a compressed biceps autograft patch according to the manufacturer’s recommendations. Both grafts were sent to pathology for evaluation of tenocyte morphology. Records were reviewed to determine if compression resulted in mechanical damage to the tenocytes at the time of biceps augmentation. Results Fifty‐five shoulder procedures and 110 samples were sent for pathology analysis. Forty‐two of the 55 (76%) specimens demonstrated morphologically normal tenocytes in both the compressed and noncompressed groups, and 7 (13%) cases showed evidence of tenocyte necrosis or mechanical damage in both groups. The difference in abnormal tenocyte morphology between the compressed and native groups was not statistically significant ( P = .625). Conclusions Autograft biceps compression into a point‐of‐care patch did not result in mechanical damage to tenocyte morphology at the time of insertion for augmentation of rotator cuff pathology. Clinical Relevance Free proximal biceps tendon compression can result in a patch that does not mechanically damage the tenocyte. The patch can be used as a biologic autograft to enhance shoulder rotator cuff repair, as well as subscapularis repair in the setting of shoulder arthroplasty.

Objectives: Augmentation of rotator cuff repair in patients at risk for retear has gained popularity. These techniques have generally consisted of allograft and xenograft patches. Recently, use of an autograft biceps from the normally discarded portion after biceps tenodesis was described as a potential patch for rotator cuff repair augmentation. As an autograft, it is free and readily available. The original description prepared the patch by placing it through a commercial skin graft preparation station. This technique results in a significant decrease in tenocyte viability, however, and results in a patch that is difficult to work with. Recently, an autograft compression plate has been employed to use as a point of care processor for adapting the discarded long head of the biceps after tenodesis into an autograft patch. The purpose of this study was to evaluate the feasibility of this point of care graft preparation method, and to specifically evaluate its effect on tenocyte viability in patients undergoing patch augmentation for rotator cuff repair. Methods: We reviewed the medical records of consecutive patients who underwent biceps tenodesis for either rotator cuff repair or anatomic shoulder arthroplasty. After tenodesis, and after 27 mm of the long head of the biceps was secured for compression into the patch, the remaining length of normally discarded tendon was longitudinally split, resulting in 2 equal lengths of remnant tendon from the same zone of the tendon. One sample was sent to pathology with no preparation, and the other was prepared as a biceps autograft patch using the autograft compression plate according to the manufacturer’s recommendations. Once prepared, this second biceps sample was sent to pathology along with the first. The request was to evaluate for tenocyte viability. Pathologists were not told which sample was compressed. Records were reviewed to determine if biceps tendon samples were viable at the time of harvest, and whether the compression process affected a change between the first and second specimen. Results: 20 consecutive patients were reviewed. All 20 biceps produced usable patches. The remnant biceps samples that were sent to pathology revealed the following: Sixteen of the 20 patients had biceps tenocyte viability that were read out as completely normal in both the compressed and non compressed samples. Of the 4 patients that did show some degree of tenocyte necrosis or death, 3 of the patients had identical findings between the compressed and non-compressed samples. Only 1/20 (5%) of the patients showed a difference between the compressed sample and the non-compressed sample, with the compressed sample demonstrating small areas of “patchy necrosis” while the non compressed sample showed normal tendon in that specimen. Conclusions: Compression of the long head of the biceps results in an autograft patch that is a promising option in rotator cuff augmentation. The method of compression plating to process the long head of the biceps remnant into an augmentation patch appears to have no significant effect on tenocyte viability, suggesting that the patch has live tenocytes at the time of point of care augmentation.

Background: Clinical trials are currently underway to investigate the efficacy of intra-articular administration of mesenchymal stromal cells (MSCs) to mitigate osteoarthritis (OA) progression in the knee. Although multiple MSC sources exist, studies have yet to determine whether differences in therapeutic efficacy exist between them. Purpose: To compare the ability of intra-articularly injected adipose-derived MSCs (AD-MSCs) and amnion-derived MSCs (AM-MSCs) to mitigate the progression of knee OA in a small animal model of spontaneous OA, as well as to compare the therapeutic potential of MSCs in hyaluronic acid (HA) and in HA only with saline (OA) controls. Study Design: Controlled laboratory study. Methods: Injections of AD-MSCs or AM-MSCs suspended in HA or HA only were performed in the rear stifle joints of 3-month-old Dunkin Hartley guinea pigs (DHGPs). Repeat injections occurred at 2 and 4 months after the initial injection in each animal. Contralateral limbs received saline injections and served as untreated controls. Subsequently, joints were analyzed for osteoarthritic changes of the cartilage and subchondral bone via histologic and biochemical analyses. To evaluate MSC retention time in the joint space, DHGPs received a single intra-articular injection of fluorescently labeled AD-MSCs or AM-MSCs, and the fluorescence intensity was longitudinally tracked via an in vivo imaging system. Results: No statistically significant differences in outcomes were found when comparing the ability of AD-MSCs and AM-MSCs to mitigate OA. However, the injection of AD-MSCs, AM-MSCs, and HA-only treatments more effectively mitigated cartilage damage compared with that of saline controls by demonstrating higher amounts of cartilage glycosaminoglycan content and improved histological proteoglycan scoring while reducing the percentage of osteophytes present. Conclusion: Intra-articular injection of AD-MSCs, AM-MSCs, or HA only was able to similarly mitigate the progression of cartilage damage and reduce the percentage of osteophytes compared with that of saline controls in the DHGP. However, this study was unable to establish the superiority of AD-MSCs versus AM-MSCs as a treatment to mitigate spontaneous OA. Clinical Relevance: MSCs demonstrate the ability to mitigate the progression of knee OA and thus may be used in a prophylactic approach to delay the need for end-stage treatment strategies.

Abstract Rotator cuff repair failure rates continue to be a challenging problem. Various methods of biological and structural augmentation of the rotator cuff have been explored to improve tendon healing after repair. We describe a technique in which biceps tendon autograft is harvested after tenodesis. The biceps tendon is then compressed into a patch that is placed over the repaired rotator cuff tendon. Repurposing the portion of the tendon that is otherwise discarded offers several advantages over other augmentations that have been used, including the biological potential of live autograft tenocytes in the patch, lower cost, and no donor‐site morbidity. Technique Video video See video under supplementary data.

Purpose We create a viable, mechanically expanded autograft long head biceps tendon (LHBT) scaffold for biologically augmenting the repair of torn rotator cuffs. Methods The proximal aspect of the tenotomized LHBTs was harvested from patients during rotator cuff repair surgery and was mechanically formed into porous scaffolds using a surgical graft expander. LHBT scaffolds were evaluated for change in area, tensile properties, and tenocyte viability before and after expansion. The ability of endogenous tenocytes derived from the LHBT scaffold to promote tenogenic differentiation of human adipose‐derived mesenchymal stromal cells (ADMSCs) was also determined. Results Autograft LHBTs were successfully expanded using a modified surgical graft expander to create a porous scaffold containing viable resident tenoctyes from patients undergoing rotator cuff repair. LHBT scaffolds had significantly increased area (length: 24.91 mm [13.91, 35.90] × width: 22.69 mm [1.87, 34.50]; P = .011) compared with the native LHBT tendon (length: 27.16 mm [2.70, 33.62] × width: 6.68 mm [5.62, 7.74]). The structural properties of the autograft were altered, including the ultimate tensile strength (LHBT scaffold: .56 MPa [.06, 1.06] vs. native LHBT: 2.35 MPa [1.36, 3.33]; P = .002) and tensile modulus (LHBT scaffold: 4.72 MPa [−.80, 1.24] versus native LHBT: 37.17 MPa [24.56, 49.78]; P = .001). There was also a reduction in resident tenocyte percent viability (LHBT scaffold: 38.52% [17.94, 59.09] vs. native LHBT: 68.87% [63.67, 74.37]; P =.004). Tenocytes derived from the LHBT scaffold produced soluble signals that initiated ADMSC differentiation into an immature tenocyte‐like phenotype, as indicated by an 8.7× increase in scleraxis ( P = .040) and a 3.6× increase in collagen type III mRNA expression ( P = .050) compared with undifferentiated ADMSC controls. Conclusions The ability to produce a viable autologous scaffold from the proximal biceps tendon having dimensions, porosity, mechanical characteristics, native ECM components, and viable tenocytes that produce bioactive signals conducive to supporting the biologic augmentation of rotator cuff repair surgery has been demonstrated. Clinical Relevance This biologically active construct may help to improve the quality of healing and regeneration at the repair site of rotator cuff tears, especially those at high risk for retear.

ABSTRACT Intervertebral disc degeneration (IVDD) is a progressive condition marked by tissue destruction and inflammation. The therapeutic effector functions of mesenchymal stem cells (MSCs) makes them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)‐ and amnion (AM)‐derived MSCs have several advantages compared with other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions. Human MSCs were cultured in media with or without supplementation of interleukin‐1β (IL‐1β) and tumor necrosis factor‐α at concentrations reportedly produced by IVDD cells. MSC proliferation and production of pro‐ and anti‐inflammatory cytokines were quantified following 24 and 48 h of culture. Additionally, the osteogenic and chondrogenic potential of AD‐ and AM‐MSCs was characterized via histology and biochemical analysis following 28 days of culture. In inflammatory culture, AM‐MSCs produced significantly more anti‐inflammatory IL‐10 (14.47 ± 2.39 pg/ml; p = 0.004) and larger chondrogenic pellets (5.67 ± 0.26 mm 2 ; p = 0.04) with greater percent area staining positively for glycosaminoglycan (82.03 ± 3.26%; p < 0.001) compared with AD‐MSCs (0.00 ± 0.00 pg/ml; 2.76 ± 0.18 mm 2 ; 34.75 ± 2.49%; respectively). Conversely, AD‐MSCs proliferated more resulting in higher cell numbers (221,000 ± 8,021 cells; p = 0.048) and produced higher concentrations of pro‐inflammatory cytokines prostaglandin E 2 (1,118.30 ± 115.56 pg/ml; p = 0.030) and IL‐1β (185.40 ± 7.63 pg/ml; p = 0.010) compared with AM‐MSCs (109,667 ± 5,696 cells; 1,291.40 ± 78.47 pg/ml; 144.10 ± 4.57 pg/ml; respectively). AD‐MSCs produced more mineralized extracellular matrix (3.34 ± 0.05 relative absorbance units [RAU]; p < 0.001) compared with AM‐MSCs (1.08 ± 0.06 RAU). Under identical inflammatory conditions, a different effector response was observed with AM‐MSCs producing more anti‐inflammatories and demonstrating enhanced chondrogenesis compared with AD‐MSCs, which produced more pro‐inflammatory cytokines and demonstrated enhanced osteogenesis. These findings may begin to help inform researchers which MSC source may be optimal for IVD regeneration. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2445–2456, 2019