Adhesions in a murine flexor tendon graft model: Autograft versus allograft reconstruction

The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.
Journal of Orthopaedic Research (Impact Factor: 2.99). 06/2008; 26(6):824-33. DOI: 10.1002/jor.20531
Source: PubMed


Reconstruction of flexor tendons often results in adhesions that compromise joint flexion. Little is known about the factors involved in the formation of flexor tendon graft adhesions. In this study, we developed and characterized a novel mouse model of flexor digitorum longus (FDL) tendon reconstruction with live autografts or reconstituted freeze-dried allografts. Grafted tendons were evaluated at multiple time points up to 84 days post-reconstruction. To assess the flexion range of the metatarsophalangeal joint, we developed a quantitative outcome measure proportional to the resistance to tendon gliding due to adhesions, which we termed the Gliding Coefficient. At 14 days post-grafting, the Gliding Coefficient was 29- and 26-fold greater than normal FDL tendon for both autografts and allografts, respectively (p < 0.001), and subsequently doubled for 28-day autografts. Interestingly, there were no significant differences in maximum tensile force or stiffness between live autograft and freeze-dried allograft repairs over time. Histologically, autograft healing was characterized by extensive remodeling and exuberant scarring around both the ends and the body of the graft, whereas allograft scarring was abundant only near the graft-host junctions. Gene expression of GDF-5 and VEGF were significantly increased in 28-day autografts compared to allografts and to normal tendons. These results suggest that the biomechanical advantages for tendon reconstruction using live autografts over devitalized allografts are minimal. This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions.

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Available from: Kjeld Søballe, Sep 15, 2014
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    • "The initial length of the tendon for post analysis was measured from the footpad to the tendon/glue interface in all cases except the 12 week time point which was measured from the toes to the interface. The tendon was then loaded onto a uniaxial tensile testing machine, Instron DynaMite 8841 (Instron, Norwood, MA) by clamping the proximal end at the glue interface and the distal end at the paw [20]. Tensile force was applied to create a distraction rate of 30 mm/min until failure. "
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    ABSTRACT: The obesity epidemic has resulted in a large increase in type 2 diabetes (T2D). While some secondary complications of T2D are well recognized and their cellular and molecular mechanisms are defined, the impact of T2D on the musculoskeletal system is less understood. Clinical evidence suggests that tendon strength and repair are compromised. Here, a mouse model of obesity and T2D recapitulates the deleterious effects of this condition on tendon repair. Male C57BL/6J mice at 5 weeks of age were placed on a high fat (HF)(60% kcal) or low fat (10% kcal) diet for 12 weeks. The flexor digitorum longus (FDL) tendon was then injured by puncturing it with a beveled needle. Progression of FDL tendon healing was assessed through biomechanical and histological analysis at 0, 7, 14 and 28 days post-injury. HF-fed mice displayed increased body weight and elevated fasting glucose levels, both consistent with T2D. No differences in biomechanical properties of the uninjured FDL tendon were observed after 12 weeks on HF versus lean diets, but decreased maximum force in uninjured tendons from HF-fed mice was observed at 24 weeks. Following puncture injury, tendons from HF-fed mice displayed impaired biomechanical properties at day 28 post injury. In support of defective repair in the HF-fed mice, histological examination of the injury site showed a smaller area of repair and lower cell content in the repair area of HF-fed mice. Insulin receptors were expressed in most cells at the injury site regardless of diet. The HF-diet mouse model of obesity and T2D reproduces the impaired tendon healing that is observed in this patient population. The exact mechanism is unknown, but we hypothesize that a cellular defect, perhaps involving insulin resistance, leads to decreased proliferation or recruitment to the injury site, and ultimately contributes to defective tendon healing.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "Adhesion and biomechanical testing was completed as previously described [7], [49]. The hind limb was disarticulated at the knee, and the FDL tendon was released from the surrounding tissue proximal to the tarsal tunnel. "
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    ABSTRACT: The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL) tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9(-/-) mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9(-/-) mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP(+)) migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9(-/-) mice with WT marrow cells resulted in greater adhesions than observed in Mmp9(-/-) mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing.
    Full-text · Article · Jul 2012 · PLoS ONE
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    • "Results might differ after cyclic testing, testing in specific applications such as a finger tendon graft, or in vivo (Hasslund et al., 2008; Webster and Werner, 1983). Moreover, allogeneic tendons may heal more slowly than autografts (Dustmann et al., 2008; Scheffler et al., 2008), neutralizing the benefit of any difference in initial strength (Maeda et al., 1997). "
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    ABSTRACT: The purpose of this study was to compare two different methods of joining tendons of similar and dissimilar sizes between recipient and donor tendons for flexor tendon grafts. Flexor digitorum profundus (FDP) and peroneus longus (PL) canine tendons were harvested and divided into four groups. The repair technique we compared was a step-cut (SC) suture and a Pulvertaft weave (PW). FDP tendons were significantly larger in diameter than PL tendons (p < 0.05). The volume of the SC repairs using either FDP or PL tendon as a graft was significantly smaller than PW repairs (p < 0.05). The ultimate load to failure and repair stiffness in FDP graft tendons significantly increased compared with the PL graft tendons (p < 0.05). The SC suture can be used as an alternative to the PW, with similar strength and less bulk for repairs using graft tendons of similar diameter. Surgeons should be aware of the effect of graft tendon size and repair method on strength and bulk when performing flexor tendon grafts.
    Full-text · Article · Apr 2012
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