There have been no studies evaluating incisional NPWT as a prophylactic treatment to prevent infection and wound dehiscence of high-risk surgical incisions. Our data demonstrate that there is a decreased incidence of wound dehiscence and total infections after high-risk fractures when patients have NPWT applied to their surgical incisions after closure. There is also a strong trend for decreases in acute infections after NPWT. Based on our data in this multicenter prospective randomized clinical trial, NPWT should be considered for high-risk wounds after severe skeletal trauma.

Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability.

Control patients developed 2 acute infections (8%) and 5 delayed infections (20%), for a total of 7 deep infections (28%), whereas NPWT patients developed 0 acute infections, 2 delayed infections (5.4%), for a total of 2 deep infections (5.4%). There is a significant difference between the groups for total infections (P = 0.024). The relative risk ratio is 0.199 (95% confidence interval: 0.045-0.874), suggesting that patients treated with NPWT were only one-fifth as likely to have an infection compared with patients randomized to the control group. NPWT represents a promising new therapy for severe open fractures after high-energy trauma.

Segmental defect regeneration has been a clinical challenge. Current tissue-engineering approach using porous biodegradable scaffolds to delivery osteogenic cells and growth factors demonstrated success in facilitating bone regeneration in these cases. However, due to the lack of mechanical property, the porous scaffolds were evaluated in non-load bearing area or were stabilized with stress-shielding devices (bone plate or external fixation). In this paper, we tested a scaffold that does not require a bone plate because it has sufficient biomechanical strength. The tube-shaped scaffolds were manufactured from poly(propylene) fumarate/tricalcium phosphate (PPF/TCP) composites. Dicalcium phosphate dehydrate (DCPD) were used as bone morphogenetic protein-2 (BMP-2) carrier. Twenty-two scaffolds were implanted in 5mm segmental defects in rat femurs stabilized with K-wire for 6 and 15 weeks with and without 10 microg of rhBMP-2. Bridging of the segmental defect was evaluated first radiographically and was confirmed by histology and micro-computer tomography (microCT) imaging. The scaffolds in the BMP group maintained the bone length throughout the duration of the study and allow for bridging. The scaffolds in the control group failed to induce bridging and collapsed at 15 weeks. Peripheral computed tomography (pQCT) showed that BMP-2 does not increase the bone mineral density in the callus. Finally, the scaffold in BMP group was found to restore the mechanical property of the rat femur after 15 weeks. Our results demonstrated that the load-bearing BMP-2 scaffold can maintain bone length and allow successfully regeneration in segmental defects.

Background Segmental bone loss remains a challenging clinical problem. A frequent mitigating factor is inadequate blood supply. Small molecules that activate the hypoxia inducible factor pathway (HIF) can be used to stimulate angiogenesis. We investigated an approach to promote healing using angiogenic and osteogenic compounds in combination with a biodegradable, weight bearing scaffold. Methods Adult rats underwent removal of a 5mm segment of femur stabilized by a cylindrical biodegradable implant and intramedullary fixation. Treatment groups included (1) saline (negative control), (2) desferrioxamine ((DFO), a HIF activator), (3) low dose rhBMP-2 (5µg), (4) DFO and low dose rhBMP-2 (5µg) or (5) rh-BMP-2 (10µg). Angiography was used to evaluate vascularity. Bone healing was assessed by radiographs, µCT, histology and biomechanical testing. Results Increased vascularity was seen at 6 weeks in the DFO treatment group. There appeared to be increased bone bridging as assessed by radiographic scores and µCT in the BMP groups, although the quantification of bone volume did not show statistically significant differences. Biomechanical testing revealed improved stiffness in the treatment groups. Conclusions DFO improved angiogenesis and stiffness of bone healing in segmental defects. BMP improved radiographic scores and stiffness. Use of angiogenic compounds in segmental bone loss is promising. Clinical Relevance Activation of the HIF pathway may prove useful for bone defects, particularly where impaired blood supply exists. The low cost approach could be useful in segmental bone defects clinically.

Our results suggest that gentamicin applied to a biodegradable scaffold is effective at decreasing radiographically defined osteomyelitis in an infected open fracture.

The purpose of this study was to evaluate the effect of low molecular weight heparin (LMWH) on fracture healing in a standard stabilized rat femur fracture model. A closed, middiaphyseal transverse fracture was created in the right femur of Long-Evans rats after insertion of a 0.8-mm K-wire into the medullary canal. Animals were randomized to receive either LMWH (70 units/kg dalteparin) or an injection of normal saline daily for 2 weeks. Animals were sacrificed at 2, 3, and 6 weeks. Fracture healing was assessed by radiographs, histology, and mechanical testing. There were no significant differences between the control and LMWH groups in the percentage of animals with radiographic bridging callus at each time point. Histologic appearance of fracture healing was similar between the control and LMWH groups. There were no significant differences in the normalized mechanical properties of the control and LMWH groups at 2 and 3 weeks. At 6 weeks, the percent torque of the LMWH group was significantly greater than the control group ( p ¼ 0.0072), however, there was no significant difference in the stiffness and energy absorption. Dalteparin, at the dosage used in this study, did not impair fracture healing in this standard stabilized rat femur fracture model. ß

Background and Purpose. A recent novel application of ultrasound therapy is the treatment of bone fractures. The aim of this study was to investigate the effect on fracture repair of ultrasound produced by a conventional therapeutic ultrasound unit as used by physical therapists. Subjects and Methods. Bilateral midshaft femur fractures were created in 30 adult male Long-Evans rats. Ultrasound therapy was commenced on the first day after fracture and introduced 5 days a week for 20 minutes a day. Each animal was treated unilaterally with active ultrasound and contralaterally with inactive ultrasound. Active ultrasound involved a 2-millisecond burst of 1.0-MHz sine waves repeating at 100 Hz. The spatially averaged, temporally averaged intensity was set at 0.1 W/cm 2 . Animals were killed at 25 and 40 days after fracture induction, and the fractures were assessed for bone mass and strength. Results. There were no differences between fractures treated with active ultrasound and fractures treated with inactive ultrasound at 25 days. However, at 40 days, active ultrasound-treated fractures had 16.9% greater bone mineral content at the fracture site than inactive ultrasound-treated fractures. This change resulted in a 25.8% increase in bone size, as opposed to an increase in bone density, and contributed to active ultrasound-treated fractures having 81.3% greater mechanical strength than inactive ultrasound-treated fractures. Discussion and Conclusion. These data indicate that ultrasound produced by a conventional therapeutic ultrasound unit as traditionally used by physical therapists may be used to facilitate fracture repair. However, careful interpretation of this controlled laboratory study is warranted until its findings are confirmed by clinical trials. [Warden SJ, Fuchs RK, Kessler CK, et al. Ultrasound produced by a conventional therapeutic ultrasound unit accelerates fracture repair.