Rat Achilles Tendon Healing Research Articles

Addition of nitric oxide via nitroflurbiprofen enhances the material properties of early healing of young rat Achilles tendons.

To determine if the addition of nitric oxide (NO) via nitroflurbiprofen (NO-flurbiprofen) would enhance rat Achilles tendon healing. Sixty-five male Sprague-Dawley rats were randomly divided into NO-flurbiprofen, flurbiprofen and vehicle groups, given drugs or vehicle subcutaneously, and their right Achilles tendon divided. Histological assessment was carried out at day 5, 10, and 15 post-operation. Healing tendon biomechanical properties and hydroxyproline content were measured at day 10. The healing Achilles tendon from the NO-flurbiprofen and flurbiprofen groups showed a better organization of extracellular collagenous matrix than that from the vehicle group. Flurbiprofen and NO-flurbiprofen decreased healing tendon cross-sectional area by 30% and 20%. This reduction was accompanied by a decreased failure load in the flurbiprofen group, but not the NO-flurbiprofen group. NO-flubiprofen prevented the reduction of body weight gain observed in the flubiprofen group. Both flurbiprofen and NO-flurbiprofen promoted better collagen reorganization during tendon healing. NO-flurbiprofen further improved tendon healing by increasing tendon stress and reducing the side effects (body weight loss) of flurbiprofen. The enhanced tendon healing by NO-flurbiprofen is likely due to the release of NO from the compound.

Adenovirus-mediated gene transfer to healing tendon––enhanced efficiency using a gelatin sponge

Adenovirus-mediated gene transfer is a potential method for enhancing tendon healing. We investigated the transfection of Ad5CMVntLacZ, an adenovirus containing the reporter gene LacZ, in primary cultured human rotator cuff tendon cells and in a rat Achilles tendon healing model in vivo. Ad5CMVempty, the adenoviral vector containing no inserted gene, was used as a control for adenoviral transfection alone. Activity of β-galactosidase,the protein expressed by LacZ gene, was measured using a β-galactosidase assay and detected visually by X-gal staining. Cultured cells were successfully transfected without impairing cell viability. Maximal β-galactosidase activity was detected when cells were transfected at the dose of 1000 PFU/cell. The duration of LacZ expression was six days with a peak value at 24 h post-transfection. A transfection rate of 100% was obtained at 5000 PFU/cell. Successful in vivo transfection by Ad5CMVntLacZ was obtained in healing rat Achilles tendon as confirmed by X-gal staining. 0.4% of tendon cells were transfected when Ad5CMVntLacZ was injected into the tendon at a dose of 10 6 PFU. The rate rose to 2% with 10 8 PFU and 3% with 10 9 PFU. The duration of LacZ expression in vivo was 17 days. Transfection efficiency was enhanced threefold and localization improved when a gelatin sponge was used to deliver the adenovirus. The results demonstrate that adenovirus can be used to deliver a gene of interest to cultured human rotator cuff tendon cells and healing tendon, with gelatin sponge implantation enhancing adenoviral transfection efficiency in vivo.

Neuronal plasticity in relation to nociception and healing of rat achilles tendon

Nerve regeneration and the occurrence of three neuropeptides; i.e. substance P (SP), calcitonin gene related peptide (CGRP) and galanin (GAL), were studied during healing of tendon rupture in the rat by semi-quantitative immunohistochemistry. The neuronal findings were related to nociception as assessed by hindpaw withdrawal latencies at thermal and mechanical tests. Experimental rupture of rat Achilles tendon––normally devoid of nerves––elicited extensive nerve ingrowth into the rupture site in the early phase of healing followed by almost complete fiber disappearance (weeks 12–16). The ingrowth of SP and CGRP positive fibers, seen already at weeks 1–2, was associated with increased nociception. Subsequently, the occurrence of GAL positive fibers at weeks 4–6 was associated with decreased nociception. An even stronger relationship to nociception during healing was observed when the rate of change in neuropeptide expression instead of the expression in absolute terms was considered, according to the “cascade” formula of SP ′+CGRP ′−GAL ′. It may prove that the observed temporal occurrence of different neuropeptides reflects a role of the peripheral nervous system in regulating synchronously nociception and healing.