An evaluation of electrical stimulation for improving periprosthetic attachment.

Transcutaneous osseointegrated implants (TOI) have been shown to improve functionality for patients with limb loss by allowing direct skeletal attachment between an exoprosthesis and host bone. However, a lengthy rehabilitation period has limited the expansion of TOI and may be accelerated with electrical stimulation. The purpose of this study was to determine the ability of direct current (DC) cathode stimulation to enhance osseointegration of intramedullary implants in skeletally matured rabbits. Bilateral implants were inserted in the hind limbs of 25 adult female rabbits. The left hind limb of each animal was continually stimulated with a potential difference of 0.55 volts based on finite element analysis predictions. After sacrifice, the limbs were divided into two groups: Group I for histology and Group II for biomechanical testing. The bone-implant construct was evaluated in the Group I animals using appositional bone index (ABI), mineral apposition rates (MAR), histological staining, and scanning electron microscopy (SEM). Group II implants were sectioned and subjected to mechanical push-out tests. Data indicated no statistical differences for ABI, MAR, and porosity between the electrically stimulated implants (ESI) and the unstimulated control implants (UCI) at three weeks and six weeks. Higher mechanical push-out forces were observed in the UCI group at six weeks (p = 0.034). Data indicated that DC cathode stimulation may improve suboptimal implant "fit and fill" as an increase in trabecular bone was noted around the cathode in the ESI group. However, longer time duration animal studies and variations in electrical modalities may be required before electrically induced osseointegration becomes clinically feasible.

Inhibition of neointimal hyperplasia in vascular grafts by sustained perivascular delivery of paclitaxel.

BACKGROUND: Neointimal hyperplasia occurs commonly at the anastomoses of arteriovenous grafts for chronic hemodialysis, causing stenosis and occlusion. Antiproliferative drugs may be effective in inhibiting hyperplasia, but local drug delivery would be required to minimize systemic side effects. We examined the feasibility of local drug delivery to inhibit neointimal hyperplasia at dialysis grafts in a canine model. METHODS: Bilateral polytetrafluoroethylene loop grafts (10-cm length and 6-mm internal diameter) were placed between the femoral artery and ipsilateral femoral vein of five mongrel dogs. At the time of surgery or 1 to 5 weeks later, 2 mL of a thermosensitive biodegradable copolymer (ReGel) mixed with 0.26 mg or 0.65 mg paclitaxel were applied to the external surface of one graft around the anastomoses to provide a depot for sustained release of the drug. ReGel alone without paclitaxel was applied to the contralateral graft as a control. The grafts and the connecting vessels were explanted at eight or nine weeks, and the cross-sections were examined histologically. The degree of hyperplasia at the anastomoses was graded by five blinded independent reviewers, with scores ranging from 0 to 5. RESULTS: The median (25th-75th percentile) hyperplasia score of both arterial and venous anastomoses was 1.80 (0.90-3.05) in the grafts treated with ReGel alone, and 0.95 (0.70-1.50) in the grafts treated with ReGel/paclitaxel (N= 8; P < 0.05 by Wilcoxon signed rank test). There were no noticeable localized or systemic complications attributed to the treatments in these animals. Paclitaxel levels in the plasma obtained from forelimb veins were undetectable (<10 ng/mL). CONCLUSION: These results suggest that the local delivery of antiproliferative agents using a thermosensitive, injectable biodegradable copolymer (ReGel) for sustained delivery is a promising strategy to inhibit neointimal hyperplasia of arteriovenous hemodialysis grafts.

The inhibitory activity of serum to prevent bacterial adhesion is mainly due to apo-transferrin.

A marked, up to 5-fold, reduction in bacterial adhesion to Tecoflex polyurethane (PU) surfaces was observed in the presence of bovine/human serum or plasma at 0.5% or higher concentrations in the medium. Further investigation of the phenomenon resulted in identification, isolation, and characterization of the serum component with the ability to significantly reduce bacterial adhesion. Upon fractionation of bovine serum by an anion exchange chromatography, protein pools were made and analyzed by immunoelectrophoresis and by polyacrylamide gel electrophoresis in the presence of SDS and were examined for their effect on the adhesion of Staphylococcus epidermidis to PU surfaces. The pool exhibiting a significant inhibitory effect was subjected to further biochemical tests, which resulted in the identification of transferrin (Tf) as its predominant protein. Bacterial adhesion studies in the presence of purified Tf revealed that holo-Tf (iron-containing form) had no influence on bacterial adhesion at any concentration. Only apo-Tf (iron-lacking form) exerted the inhibitory effect, in a dose responsive manner at concentrations of 10 microg/mL or higher. Bacteria remained viable when suspended at the low apo-Tf concentrations, sufficient to prevent bacterial adhesion.

The effect of apo-transferrin on bacterial adhesion to biomaterials.

Apo-transferrin (apo-Tf), the iron deficient form of Tf, has been identified previously as a potent inhibitor of Staphylococcus epidermidis adhesion to polyurethane surfaces. In this study, the ability of apo-Tf to suppress the adhesion of two other strains of bacteria, namely a Gram-positive Staphylococcus aureus and a Gram-negative Pseudomonas aeruginosa to several biomaterials, including polystyrene, polymethylmethacrylate, and silicone, is documented. The presence of apo-Tf in the medium at 20 microg/ml lowered bacterial adhesion to all tested biomaterials more than fourfold. Moreover, apo-Tf exerted its inhibitory activity even when protein coated surfaces were used as substrates for bacterial adhesion. To emphasize the importance of apo-Tf in the prevention of bacterial adhesion, human serum was depleted of Tf, employing affinity chromatography, and was shown to lose its inhibitory activity toward bacterial adhesion. Upon addition of apo-Tf to Tf-depleted serum, the activity was reestablished, resulting in a marked reduction in the number of bacteria adhered to the surfaces. Following the enzymatic deglycosylation, apo-Tf retained its ability to prevent bacterial adhesion. These results indicate that the carbohydrate moiety does not seem to play a role in this activity. The presented data provide the evidence that the inhibitory activity of apo-Tf is not bacterial strain specific and that the presence of apo-Tf in the medium results in a significant reduction of bacterial adhesion to a variety of neat and/or protein coated surfaces.