Direct current stimulation for spine fusion in a nicotine exposure model.

BACKGROUND CONTEXT: Decreased effectiveness in spinal fusion procedures in patients who smoke before, during, or after the operation has been noted in several clinical studies. In previous work, direct current (DC) electrical stimulation has been shown to enhance inter-transverse process fusion in a rabbit model. PURPOSE: To test the efficacy of DC stimulation on bone healing in spinal fusion in rabbits exposed to nicotine. STUDY DESIGN/SETTING: A randomized and controlled interventional study. METHODS: Thirty male New Zealand white rabbits received a single level posterolateral, inter-transverse process fusion with autologous iliac crest bone. One group (control) acted as a control without nicotine or electrical stimulation. A second group (Nic) received a continuous dose of nicotine via a transdermal patch to simulate a heavy smoker, and a third group, nicotine/stimulator group (Nic/Stim), additionally received a 100-microamp DC stimulator. The fusion masses (L5-L6) and the adjacent unfused control segment (L4-L5) were evaluated radiographically, manually, and biomechanically. RESULTS: The Nic group showed significantly higher fusion rate compared with the control group. The Nic/Stim group also demonstrated significantly higher fusion rate and X-ray trabeculation compared with the control group. However, the Nic/Stim group was not significantly higher than the Nic group in fusion rate or X-ray trabeculation. CONCLUSIONS: Nicotine significantly improved fusion rate compared with controls, and DC stimulation significantly increased X-ray trabeculation of nicotine treated rabbits compared with controls.

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats.

Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly(lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici's collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats.

Effect of Head Position on Intraocular Pressure During Lumbar Spine Fusion: A Randomized, Prospective Study.

BACKGROUND: Ischemic optic neuropathy resulting in visual loss is a rare but devastating complication of spine surgery. Elevated intraocular pressure (IOP) results in decreased perfusion and possibly ischemic optic neuropathy. We performed a randomized, prospective trial to evaluate the effect of head positioning on IOP during lumbar spine fusion. METHODS: The study included fifty-two patients treated at one institution. Inclusion criteria were a lumbar spine fusion and an age of eighteen to eighty years. Exclusion criteria were a diagnosis of tumor, infection, or traumatic injury or a history of eye disease, ocular surgery, cervical spine surgery, chronic neck pain, or cervical stenosis. The control group underwent the surgery with the head in neutral and the face parallel to the level operating room table whereas, in the experimental group, the neck was extended so that the face had a 10° angle of inclination in relation to the table. IOP measurements were recorded along with the corresponding blood pressure and PCO2 values at the same time points. The primary outcome measure was the change in intraocular pressure (ΔIOP, defined as the maximum IOP minus the initial IOP). RESULTS: Analysis of covariance (ANCOVA) was used for categorical risk factors, and regression analysis was used for continuous risk factors. The mean ΔIOP, corrected for duration of surgery, was significantly (p = 0.0074) lower in the group treated with the head elevated than it was in the group treated with the head in neutral (difference between the two groups, 4.53 mm Hg [95% confidence interval, 1.29 to 7.79 mm Hg]). No patient sustained visual loss or any cervical-spine-related complications. CONCLUSIONS: Head elevation for adult lumbar spine fusion performed with the patient prone resulted in significantly lower IOP measurements than those seen when the operation was done with the patient's head in neutral. As lower IOP correlates with increased optic nerve perfusion, this intervention could mitigate the risk of perioperative blindness after spine surgery done with the patient prone.

The response of rabbit patellar tendons after autologous blood injection.

PURPOSE: Blood is a rich source of growth factors that can stimulate fibrocyte migration and help induce neovascular ingrowth. These properties may be able to stimulate a healing response in chronic degeneration of a tendon (tendonosis). The purpose of this study was to assess the biomechanical and histological effects of autologous blood injection on animal tendons. METHODS: New Zealand white rabbit left side patellar tendons were injected with 0.15 cc of autologous blood. We then compared the mechanical properties and histology to the normal right patellar tendon at 6 and 12 wk. RESULTS: At 6 and 12 wk after the injection, there were no differences in the histology compared with normal tendon tissue, and there were no significant changes in tendon stiffness. Biomechanically, the tendons were not damaged at 6 wk after the injection. By 12 wk, tendons that were injected with blood were significantly (P < 0.014) stronger. CONCLUSION: We found that injecting blood directly into normal tendons appears safe. Further evaluation of this technique would appear indicated.

Additive effects of exogenous IL-12 supplementation and antibiotic treatment in infection prophylaxis.

The increasing clinical incidence and host risk of open fracture-associated infections, as well as the reduced effectiveness of conventional antibiotics to treat such infections, have driven the development of new therapies for the prophylaxis of open fracture-associated infections. We investigated percutaneous supplementation of a natural cytokine (i.e., interleukin 12p70 or IL-12) at an open fracture site to reduce open fracture-associated infections. We also determined the efficacy of the combination therapy of IL-12 and conventional antibiotic therapy in the prophylaxis of open fracture-associated infections. An open femur fracture infection model was produced by direct inoculation of a clinical isolate of Staphylococcus aureus after creating a femur fracture using rats. The animals were assigned to one of four groups: no drug administration, percutaneous supplementation of IL-12, intraperitoneal administration of the antibiotic ampicillin, or percutaneous IL-12 in combination with intraperitoneal ampicillin. Animals were euthanized at postoperative days 6, 10, 14, and 21. Percutaneous IL-12 led to a reduction in infection at postoperative days 6 and 10. For the first time, exogenous IL-12 was found to have additive effects in the prevention of infection when combined with conventional treatment (i.e., antibiotic therapy). Combination therapy of ampicillin and IL-12 substantially reduced the infection rate at postoperative day 6 and also decreased the time needed for complete inhibition of infection. Therefore, exogenous IL-12, providing a mechanism of protection independent of antibiotic resistance, complements the routine use of antibiotics.

Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open fractures.

The increasing incidence of bacterial infection and the appearance of Staphylococcus aureus (S. aureus) strains that are resistant to commonly used antibiotics has made it important to develop non-antibiotic approaches for infection prevention. The aim of this study was to develop local monocyte chemoattractant protein-1 (MCP-1) and interleukin-12 p70 (IL-12 p70) therapies to prevent S. aureus infection by enhancing the recruitment and activation of macrophages, which are believed to play an important role in infection prevention as the first line of defense against invading pathogens. Nanocoating systems for MCP-1 and IL-12 p70 deliveries were prepared, and their release characteristics desirable for infection prevention in open fractures were explored. Local MCP-1 therapy reduced S. aureus infection and influenced white blood cell populations, and local IL-12 p70 treatment had a more profound effect on preventing S. aureus infection. No synergistic relationship in decreasing S. aureus infection was observed when MCP-1 and IL-12 p70 treatments were combined. This reported new approach may reduce antibiotic use and antibiotic resistance.

An animal model for open femur fracture and osteomyelitis--Part II: Immunomodulation with systemic IL-12.

Infection resulting from open fracture is a common problem in orthopedics. The purpose of this project was to study the effect of Interleukin-12 (IL-12) systemic therapy on a previously established open fracture model. One hundred seven male Sprague-Dawley rats were assigned to five groups: (1) normal (baseline), (2) control (controlled for anesthesia), (3) fracture, (4) staph, and (5) staph and IL-12 (SIL). Each group was divided into four time periods: 6, 10, 14, and 21 days after injury and fixation. The operative groups had a standardized femur fracture and fixation using a Kirschner wire as an intramedullary device. The two infection groups (staph and SIL) were inoculated with Staphylococcus aureus following fracture and fixed with an identical technique. The SIL group was treated with systemic IL-12 for a total of 10 doses over 10 days. Significantly decreased serum IL-12 levels were noted at day 10 in the operative groups compared to the normal and control groups. The SIL group showed significantly higher macrophage activation levels and total platelet counts at day 21 compared to all the other groups. The overall infection rate was not changed by IL-12 supplementation; however, bacterial qualitative growth scores were significantly lower in the SIL group at day 10, which corresponded to the lowest level of systemic IL-12 in the fracture group.

An animal model for open femur fracture and osteomyelitis: Part I.

Infection is an everyday problem in orthopaedics and is quite common in open fracture management. To study this process and provide a basis to prevent infection, we developed a model that includes trauma (blunt fracture in the fashion of Bonnarens and Einhorn), surgical stabilization (standardized intramedullary K-wire fixation), and infection (Staphylococcus aureus inoculum). In this two-part study, we found that 10(2) colony-forming units of inoculum produced an optimal infection rate of 90-100%, which substantially challenged the immune system without overwhelming sepsis. We hypothesized that, in traumatic fractures, there is a specific immunological response that may lead to an increased rate of infection. In Part 2, we demonstrated immunosuppression (decreased Interleukin-12 levels) at days 6, 10, and 12 after fracture fixation versus nonfractured control groups (p < 0.05). This study describes a rat model of femur factures with osteomyelitis that allows investigation of posttraumatic immunosuppression.