Short-term electrical stimulation to promote nerve repair and functional recovery in a rat model.

PURPOSE: To evaluate the effect of duration of electrical stimulation on peripheral nerve regeneration and functional recovery. Based on previous work, we hypothesized that applying 10 minutes of electrical stimulation to a 10-mm rat sciatic nerve defect would significantly improve nerve regeneration and functional recovery compared with the non-electrical stimulation group. METHODS: A silicone tube filled with a collagen gel was used to bridge a 10-mm nerve defect in rats, and either 10 minutes or 60 minutes of electrical stimulation was applied to the nerve during surgery. Controls consisted of a silicone tube with collagen gel and no electrical stimulation or an isograft. We analyzed recovery over a 12-week period, measuring sciatic functional index and extensor postural thrust scores and concluding with histological examination of the nerve. RESULTS: Functional assessment scores at week 12 increased 24% in the 10-minute group as compared to the no stimulation control group. Electrical stimulation of either 10 or 60 minutes improved the number of nerve fibers over no stimulation. Additionally, the electrical stimulation group's histomorphometric analysis was not different from the isograft group. CONCLUSIONS: Several previous studies have demonstrated the effectiveness of 60-minute stimulations on peripheral nerve regeneration. This study demonstrated that an electrical stimulation of 10 minutes enhanced several functional and histomorphometric outcomes of nerve regeneration and was overall similar to a 60-minute stimulation over 12 weeks. CLINICAL RELEVANCE: Decreasing the electrical stimulation time from 60 minutes to 10 minutes provided a potential clinically feasible and safe method to enhance nerve regeneration and functional recovery.

Resorbable, amino acid-based poly(ester urea)s crosslinked with osteogenic growth peptide with enhanced mechanical properties and bioactivity.

Materials currently used for the treatment of bone defects include ceramics, polymeric scaffolds and composites, which are often impregnated with recombinant growth factors and other bioactive substances. While these materials have seen instances of success, each has inherent shortcomings including prohibitive expense, poor protein stability, poorly defined growth factor release and less than desirable mechanical properties. We have developed a novel class of amino acid-based poly(ester urea)s (PEU) materials which are biodegradable in vivo and possess mechanical properties superior to conventionally used polyesters (<3.5 GPa) available currently to clinicians and medical providers. We report the use of a short peptide derived from osteogenic growth peptide (OGP) as a covalent crosslinker for the PEU materials. In addition to imparting specific bioactive signaling, our crosslinking studies show that the mechanical properties increase proportionally when 0.5% and 1.0% concentrations of the OGP crosslinker are added. Our results in vitro and in an in vivo subcutaneous rat model show the OGP-based crosslinkers, which are small fragments of growth factors that are normally soluble, exhibit enhanced proliferative activity, accelerated degradation properties and concentration dependent bioactivity when immobilized.

Evaluation of embolic protection devices for fat emboli prevention.

BACKGROUND: Patients with acutely treated femoral shaft fractures with reamed intramedullary nailing are at risk for acute respiratory distress syndrome due to liberation of bone marrow fat particles that travel to the lung and cause damage to the parenchyma. The purpose of this study was to demonstrate: (1) the ability of clinically applicable embolic protection devices to capture such particles; (2) how such a device affects cardiopulmonary function after reamed intramedullary nailing; and (3) evaluation of lung pathology to determine whether filtration affects pulmonary embolic load. METHODS: A total of 12 canines were anesthetized, and hemodynamic monitoring was established. Carotid embolic protection devices were introduced into the iliac vein, and ipsilateral intramedullary reaming and nailing was performed. Cardiopulmonary parameters were recorded at timed intervals up to 60 minutes after the procedure. The control group (n = 4) was compared with groups treated with Accunet (n = 4) and Spider (n = 4) filters. A blinded histopathological review was performed on lung specimens to determine the average number of emboli per section and to measure the area (mm(2)) of embolic load by digital image analysis. RESULTS: Gross inspection of the embolic protection devices showed the presence of bone marrow debris. A significant change was observed in pH levels (control = -0.052, filters = +0.005; P < .05) within the 60 minutes after intramedullary nailing. Serum bicarbonate (meq/dL) values were noted to have similar changes of -2.7 and -1.8 at 10 and 60 minutes, whereas the experimental group was +0.6 and +0.8 at the same time intervals (P =.01 and .0004, respectively). Pulmonary measurements for pO2 and oxygen saturation were analogous to the serum parameters with decreases in the control group in comparison with the filter groups. The mean numbers of emboli and area measurements of embolic load were significantly reduced in the filter group (all P < .01). CONCLUSIONS: Embolic protection devices were effective in capturing embolic debris from reamed intramedullary nailing of lower extremity long bones and demonstrated a protective effect on pulmonary function and significantly decreased the number and size of emboli in the lung. Based on these findings, patients with long bone fractures at risk for pulmonary complications and acute respiratory distress syndrome could benefit from the placement of embolic protection devices prior to intramedullary fixation. While this study utilized filtration devices designed for carotid embolic protection, further study is warranted to determine optimal filter design in this setting.

Resveratrol exerts differential effects in vitro and in vivo against ovarian cancer cells.

Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.