Dataset Information

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

ABSTRACT: BACKGROUND:Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. MATERIALS AND METHODS:In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. RESULTS:Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. CONCLUSION:Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

SUBMITTER: Thangarajah T

PROVIDER: S-EPMC5015825 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

Thangarajah Tanujan T Shahbazi Shirin S Pendegrass Catherine J CJ Lambert Simon S Alexander Susan S Blunn Gordon W GW

PloS one 20160908 9

<h4>Background</h4>Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic ...[more]

PMID: 27606597

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Project description:PurposeTo define the topographic anatomy of the footprint of the adductor longus origin on the pubis and its underlying bony morphology to better inform surgical repair of adductor longus tendon injuries.MethodsFive cadaveric pelvis specimens were dissected, making 10 adductor footprints available for analysis. The adductor longus tendon origin was isolated and the surrounding tissue debrided. The circumference of the tendinous attachment to the pubic crest was marked before excising the tendon and fibrocartilage enthesis from the pubis. Radiopaque paint was prepared by mixing 30 mL of all-purpose acrylic paint (Anita's no. 11150 Island Blue; Rust-Oleum Corp, Vernon Hills, IL) with 15g of E-Z-HD 98% w/w barium sulfate (Bracco Diagnostics Inc., Anjou Quebec, Canada) and applied to the marked footprint. The specimens underwent a 1.0-mm slice computed tomographic scan with 3-dimensional reconstructions. Synapse PACS (FujiFilm, Valhalla, NY) software for measurements of the tendon footprint and underlying bone.ResultsAverage age and weight of the specimens at the time of death was 37 years and 204.6 ± 48.7 lbs, respectively. The width and length of the tendon origin was 12.0 ± 1.1 mm and 10.9 ± 1.1 mm, respectively. The distance of the center of the footprint from the center of the pubic tubercle was 8.5 ± 1.4 mm lateral and 12.2 ± 0.4 mm caudal. The osseous thickness underlying the footprint was 18.7 ± 3.7 mm at an angle of 34.5 ± 1.5° in relation to the sagittal plane. The correlation between specimen body weight and the thickness of the bone underlying the footprint was strongly positive (r = 0.92).ConclusionsWe found that there is a consistent angle from the center of the adductor longus tendon footprint to the point of maximal underlying bony thickness, as well as a positive correlation between body mass index and osseous thickness, which may inform anatomic reattachment of this tendon.Clinical relevanceOur findings will assist surgeons in identifying the footprint of the adductor longus tendon and safely perform anatomic repair of adductor longus tendon avulsions.

Project description:Adipose-derived stem cells (ASCs) are multipotent and immune-privileged mesenchymal cells, making them ideal candidates for therapeutic purposes to manage tendon disorders. Providing safe and regulated cell therapy products to patients requires adherence to good manufacturing practices. To this aim we investigated the in vitro tenogenic differentiation potential of ASCs using a chemically defined serum-free medium (SF) or a xenogenic-free human pooled platelet lysate medium (hPL) suitable for cell therapy and both supplemented with CTGF, TGF?-3, BMP-12 and ascorbic acid (AA) soluble factors. Human ASCs were isolated from 4 healthy donors and they were inducted to differentiate until 14 days in both hPL and SF tenogenic media (hPL-TENO and SF-TENO). Cell viability and immunophenotype profile were analysed to evaluate mesenchymal stem cell (MSC) characteristics in both xenogenic-free media. Moreover, the expression of stemness and tendon-related markers upon cell differentiation by RT-PCR, protein staining and cytofluorimetric analysis were also performed. Our results showed the two xenogenic-free media well support cell viability of ASCs and maintain their MSC nature as demonstrated by their typical immunophenototype profile and by the expression of NANOG, OCT4 and Ki67 genes. Moreover, both hPL-TENO and SF-TENO expressed significant high levels of the tendon-related genes SCX, COL1A1, COL3A1, COMP, MMP3 and MMP13 already at early time points in comparison to the respective controls. Significant up-regulations in scleraxis, collagen and tenomodulin proteins were also demonstrated at in both differentiated SF and hPL ASCs. In conclusion, we demonstrated firstly the feasibility of both serum and xenogenic-free media tested to culture ASCs moving forward the GMP-compliant approaches for clinical scale expansion of human MSCs needed for therapeutical application of stem cells. Moreover, a combination of CTGF, BMP-12, TGF?3 and AA factors strongly and rapidly induce human ASCs to differentiate into tenocyte-like cells.

Project description:Our purpose was to determine whether a bioresorbable interference screw coated with a hydroxyapatite-based mineral layer designed to release an engineered peptide growth factor (linkBMP-2 [where "BMP-2" indicates bone morphogenetic protein 2]) improved tendon-bone healing compared with a screw without coating.Tagged linkBMP-2 peptides were used to quantify binding efficiency and release kinetics on 9 mineral-coated BIORCI screws (Smith & Nephew, Andover, MA). Fourteen mature female sheep were used in this study. In each of the 14 sheep, each stifle was randomized to either receive a linkBMP-2-coated or uncoated interference screw (n = 14 per treatment). The sheep were euthanized at 6 weeks after surgery. Eight sheep were subjected to biomechanical testing for peak load at failure and stiffness, and six sheep were used for histologic analysis according to a semiquantitative scoring scale.The linkBMP-2 molecule bound efficiently to the surface of mineral-coated interference screws. Over 80% of the initially bound linkBMP-2 was released during a 6-week time frame in vitro. Peak load at failure in the linkBMP-2-coated interference screw group (mean +/- SD, 449.3 +/- 84.7 N) was not significantly different from that in the uncoated group (421.0 +/- 61.8 N) (P = .22). Stiffness in the linkBMP-2-coated interference screw group (157.3 +/- 39.6 N/mm) was not significantly different from that in the uncoated group (140.6 +/- 20.3 N/mm) (P = .12). Histologic analysis showed that the tendons in the linkBMP-2-coated interference screw group had higher scores (better) than the uncoated group. In the linkBMP-2-coated interference screw group, mesenchymal cells were present at the interface between screw and tendon, whereas these cells were not present in the uncoated group.We found that linkBMP-2 can be bound onto a mineral-coated BIORCI interference screw surface and subsequently released from the screw surface in a sustained manner. The histologic result of this study showed that the linkBMP-2-coated interference screw significantly improved the histologic scores of early tendon-bone healing in this sheep model.This linkBMP-2 coating material may improve early tendon/ligament fixation.

Dataset Information

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

Publications

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

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