Are critical size bone notch defects possible in the rabbit mandible?

OBJECTIVES: Small animal maxillofacial models, such as non-segmental critical size defects (CSDs) in the rabbit mandible, need to be standardized for use as preclinical models of bone regeneration to mimic clinical conditions such as maxillofacial trauma. The objective of this study is the establishment of a mechanically competent CSD model in the rabbit mandible to allow standardized evaluation of bone regeneration therapies. MATERIALS AND METHODS: Three sizes of bony defect were generated in the mandibular body of rabbit hemi-mandibles: 12 mm×5 mm, 12 mm×8 mm, and 15 mm×10 mm. The hemi-mandibles were tested to failure in 3-point flexure. The 12 mm×5 mm defect was then chosen for the defect size created in the mandibles of 26 rabbits with or without cautery of the defect margins and bone regeneration was assessed after 6 and 12 weeks. Regenerated bone density and volume were evaluated using radiography, micro-computed tomography, and histology. RESULTS: Flexural strength of the 12 mm×5 mm defect was similar to its contralateral; whereas the 12 mm×8 mm and 15 mm×10 mm groups carried significantly less load than their respective contralaterals (P<0.05). This demonstrated that the 12 mm×5 mm defect did not significantly compromise mandibular mechanical integrity. Significantly less (P<0.05) bone was regenerated at 6 weeks in cauterized defect margins compared to controls without cautery. After 12 weeks, the bone volume of the group with cautery increased to that of the control without cautery after 6 weeks. CONCLUSION: An empty defect size of 12 mm×5 mm in the rabbit mandibular model maintains sufficient mechanical stability to not require additional stabilization. However, this defect size allows for bone regeneration across the defect. Cautery of the defect only delays regeneration by 6 weeks suggesting that the performance of bone graft materials in mandibular defects of this size should be considered with caution.

Localized low-dose rhBMP-2 is effective at promoting bone regeneration in mandibular segmental defects.

At least 26% of recent battlefield injuries are to the craniomaxillofacial (CMF) region. Recombinant human bone morphogenetic protein 2 (rhBMP-2) is used to treat CMF open fractures, but several complications have been associated with its use. This study tested the efficacy and safety of a lower (30% recommended) dose of rhBMP-2 to treat mandibular fractures. rhBMP-2 delivered via a polyurethane (PUR) and hydroxyapatite/ß-tricalcium phosphate (Mastergraft®) scaffold was evaluated in a 2 cm segmental mandibular defect in minipigs. Bone regeneration was analyzed at 4, 8, and 12 weeks postsurgery using clinical computed tomography (CT) and rhBMP-2, and inflammatory marker concentrations were analyzed in serum and surgery-site drain effluent. CT scans revealed that pigs treated with PUR-Mastergraft® + rhBMP-2 had complete bone bridging, while the negative control group showed incomplete bone-bridging (n = 6). Volumetric analysis of regenerated bone showed that the PUR-Mastergraft® + rhBMP-2 treatment generated significantly more bone than control by 4 weeks, a trend that continued through 12 weeks. Variations in inflammatory analytes were detected in drain effluent samples and saliva but not in serum, suggesting a localized healing response. Importantly, the rhBMP-2 group did not exhibit an excessive increase in inflammatory analytes compared to control. Treatment with low-dose rhBMP-2 increases bone regeneration capacity in pigs with mandibular continuity defects and restores bone quality. Negative complications from rhBMP-2, such as excessive inflammatory analyte levels, were not observed. Together, these results suggest that treatment with low-dose rhBMP-2 is efficacious and may improve safety when treating CMF open fractures. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1491-1503, 2019.

Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation.

OBJECTIVES: To validate a critical-size mandibular bone defect model in miniature pigs. MATERIALS AND METHODS: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. RESULTS: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. CONCLUSION: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

Autologous Graft Thickness Affects Scar Contraction and Quality in a Porcine Excisional Wound Model.

BACKGROUND: Texture, color, and durability are important characteristics to consider for skin replacement in conspicuous and/or mobile regions of the body such as the face, neck, and hands. Although autograft thickness is a known determinant of skin quality, few studies have correlated the subjective and objective characters of skin graft healing with their associated morphologic and cellular profiles. Defining these relationships may help guide development and evaluation of future skin replacement strategies. METHODS: Six-centimeter-diameter full-thickness wounds were created on the back of female Yorkshire pigs and covered by autografts of variable thicknesses. Skin quality was assessed on day 120 using an observer scar assessment score and objective determinations for scar contraction, erythema, pigmentation, and surface irregularities. Histological, histochemical, and immunohistochemical assessments were performed. RESULTS: Thick grafts demonstrated lower observer scar assessment score (better quality) and decreased erythema, pigmentation, and surface irregularities. Histologically, thin grafts resulted in scar-like collagen proliferation while thick grafts preserves the dermal architecture. Increased vascularity and prolonged and increased cellular infiltration were observed among thin grafts. In addition, thin grafts contained predominately dense collagen fibers, whereas thick grafts had loosely arranged collagen. α-Smooth muscle actin staining for myofibroblasts was observed earlier and persisted longer among thinner grafts. CONCLUSIONS: Graft thickness is an important determinant of skin quality. High-quality skin replacements are associated with preserved collagen architecture, decreased neovascularization, and decreased inflammatory cellular infiltration. This model, using autologous skin as a metric of quality, may give a more informative analysis of emerging skin replacement strategies.

Operative utilization following severe combat-related burns.

The goal of burn surgical therapy is to minimize mortality and to return survivors to their preinjury state. Prompt removal of the burn eschar, early durable coverage, and late corrections of functional deformities are the basic surgical principles. The operative burden, while presumed to be substantial and significant, is neither well described nor quantified. The burn registry at the U.S. Institute of Surgical Research Burn Center was queried from March 2003 to August 2011 for all active duty burn admissions; active duty subjects were chosen to eliminate subject follow-up as a significant variable. Subject demographics including age, sex, branch of service, injury type, injury severity score, transfusion, allograft use, length of stay, mechanism of injury, and survival were tabulated as were their percentage TBSA, specific body region involvement, and nature and dates of operations performed. Univariate analysis and multiple logistic regressions were performed to determine independent factors which predict early and late operative burden. In the 8-year study period, 864 active duty patients were admitted to the burn center. Among them, 569 (66%) were operative in nature. The operations that were performed during acute hospitalization were 62%, while the remaining 38% were performed following discharge. A linear relationship exists between TBSA and the number of acute operations with an average of one acute operation required per 5% TBSA. No direct relationships however were found between TBSA and the number of reconstructive operations. Based on multiple logistic regression, battle vs nonbattle (odds ratio [OR], 0.559; 95% confidence interval [CI], 0.298-1.050; P = .0706), injury severity score (OR, 1.021; 95% CI, 1.003-1.039; P = .0222), intensive care unit length of stay (OR, 1.076; 95% CI, 1.053-1.099; P ≤ .0001), allograft use (OR, 2.610; 95% CI, 1.472-4.628; P = .0010), and TBSA of the trunk (OR, 0.982; 95% CI, 0.965-1.000; P = .0439) (but not overall TBSA) were associated with a high acute operative burden. Battle vs nonbattle (OR, 0.546; 95% CI, 0.360-0.829; P = .0045), and TBSA of the upper extremities (OR, 1.008; 95% CI, 1.002-1.013; P = .0042) were noted to be significant variables in predicting late reconstruction operations. The operative burden of burn, not previously well characterized, consists of operations performed during as well as after the initial hospitalization. While injury severity and truncal involvement are significant determinants of acute surgical therapy, the presence of upper extremity burns is a significant determinant of reconstruction following discharge.

Combat-related facial burns: analysis of strategic pitfalls.

PURPOSE: Burns constitute approximately 10% of all combat-related injuries to the head and neck region. We postulated that the combat environment presents unique challenges not commonly encountered among civilian injuries. The purpose of the present study was to determine the features commonly seen among combat facial burns that will result in therapeutic challenges and might contribute to undesired outcomes. MATERIALS AND METHODS: The present study was a retrospective study performed using a query of the Burn Registry at the US Army Institute of Surgical Research Burn Center for all active duty facial burn admissions from October 2001 to February 2011. The demographic data, total body surface area of the burn, facial region body surface area involvement, and dates of injury, first operation, and first facial operation were tabulated and compared. A subset analysis of severe facial burns, defined by a greater than 7% facial region body surface area, was performed with a thorough medical record review to determine the presence of associated injuries. RESULTS: Of all the military burn injuries, 67.1% (n = 558) involved the face. Of these, 81.3% (n = 454) were combat related. The combat facial burns had a mean total body surface area of 21.4% and a mean facial region body surface area of 3.2%. The interval from the date of the injury to the first operative encounter was 6.6 ± 0.8 days and was 19.8 ± 2.0 days to the first facial operation. A subset analysis of the severe facial burns revealed that the first facial operation and the definitive coverage operation was performed at 13.45 ± 2.6 days and 31.9 ± 4.1 days after the injury, respectively. The mortality rate for this subset of patients was 32% (n = 10), with a high rate of associated inhalational injuries (61%, n = 19), limb amputations (29%, n = 9), and facial allograft usage (48%, n = 15) and a mean facial autograft thickness of 10.5/1,000th in. CONCLUSIONS: Combat-related facial burns present multiple challenges, which can contribute to suboptimal long-term outcomes. These challenges include prolonged transport to the burn center, delayed initial intervention and definitive coverage, and a lack of available high-quality color-matched donor skin. These gaps all highlight the need for novel anti-inflammatory and skin replacement strategies to more adequately address these unique combat-related obstacles.

In vitro characterization of scaffold-free three-dimensional mesenchymal stem cell aggregates.

Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation along multiple cell lineages and have potential applications in a wide range of therapies. These cells are commonly cultured as monolayers on tissue culture plastic but possibly lose their cell-specific properties with time in vitro. There is growing interest in culturing adherent cells via three-dimensional (3D) techniques in order to recapitulate 3D in vivo conditions. We describe a novel method for generating and culturing rabbit MSCs as scaffold-free 3D cell aggregates by using micropatterned wells via a forced aggregation technique. The viability and proliferative capability of MSC aggregates were assessed via Live/Dead staining and 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Enzyme-linked immunosorbent assay and antibody-based multiplex protein assays were used to quantify released growth factors and chemokines. The gene expression profile of MSCs as 3D aggregates relative to MSCs grown as monolayers was evaluated via quantitative real-time polymerase chain reaction. The rabbit MSCs were able to form compact cell aggregates and remained viable in 3D culture for up to 7 days. We also demonstrated enhanced gene and protein expression related to angiogenesis and wound healing in MSCs cultured under 3D conditions. In vitro tube formation and scratch assay revealed superior neovessel formation and greater cell recovery and migration in response to 3D conditioned media after wounding. Our data further suggest that adipose-derived stem cell aggregates have greater potential than dermal fibroblasts or bone-marrow-derived MSCs in accelerating wound healing and reducing scarring.

Proceedings from the 2013 American Association of Oral and Maxillofacial Surgeons Research Summit.

The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted.

Non-battle craniomaxillofacial injuries from U.S. military operations.

INTRODUCTION: Non-battle injuries (NBIs) can be a source of significant resource utilization for the armed forces in a deployed setting. While the incidence and severity of craniomaxillofacial (CMF) battle injuries (BIs) have reportedly increased in the ongoing U.S. military conflicts in Iraq and Afghanistan, the prevalence and the nature of NBIs are not well described. MATERIAL AND METHODS: The Joint Theater Trauma Registry was queried from October 2001 to February 2011, covering Operations Enduring Freedom and Iraqi Freedom, for both NBIs and BIs to the CMF region. Patient demographics, injury severity score, mechanism and type of injury were included in the query. Using ICD-9 diagnosis codes, CMF injuries were classified according to type (wounds, fractures, burns, vascular injuries, and nerve injuries). Statistical analysis was performed for comparative analysis. RESULTS: NBIs constituted 24.3% of all patients with CMF injuries evacuated to a regional combat support hospital (CMF BIs 75.4%). These injuries were characterized by blunt trauma, most commonly motor vehicle collisions (37%), and falls (20%). As compared to CMF BIs, CMF NBIs resulted in less mortality (1.3% vs. 3.1%, p < 0.0001), fewer injuries per patient (1.87 vs. 2.26, p = 0.055), and a decreased severity score (ISS) (8.38 vs. 12.98, p < 0.0001). However, a significant percentage of CMF NBIs still required evacuation out of theater (27.8% of NBIs vs. 42.2% of BIs, p < 0.0001), depleting the combat strength of the deployed forces. CONCLUSIONS: CMF NBIs accounted for a substantial portion of total CMF injuries. Though characterized predominantly by blunt trauma with an overall better prognosis, its burden to the limited resources of a deployment can be significant. This descriptive study highlights the need to allocate appropriate resources for treatment of these injuries as well as strategies to reduce both its incidence and severity. LEVEL OF EVIDENCE: IV Prognostic.

Characterization and management of mandibular fractures: lessons learned from Iraq and Afghanistan.

Fractures of the mandible are among the most common facial injuries. Invasiveness of treatment should be determined by the extent of injury: degree of displacement, number of fractures, the patient's health status, and concomitant injuries. Complex, comminuted, and avulsive injuries frequently seen in combat will require coordination with multiple specialties to provide the best treatment. Stabilization treatment with arch bars or external fixators and splints is often desirable when fractures are highly comminuted or the soft tissue envelope is compromised by tissue loss or burns. In severe injuries, many times reconstruction will take several surgeries. Debridement of necrotic tissue and devascularized bone and skin grafting often are necessary before reconstruction. Microvascular or myocutaneous flaps should be considered with significant tissue loss and osteocutaneous flaps when large continuity defects are present. Most mandible fractures are repaired in a single operation. Those caused by explosives and high-velocity projectiles are more complex. Research should continue to focus on improving outcomes for these patients. Advances in tissue engineering, bone regeneration, and composite tissue allografting will have to continue if we hope to restore facial form and function for our combat wounded.

Characterization of skin allograft use in thermal injury.

This study provides objective data on the practice of allograft usage in severely burned patients. Furthermore, gaps in our knowledge are identified, and areas for further research are delineated. Using an institutional review board-approved protocol, active duty military patients injured while deployed in support of overseas contingency operations and treated at our burn center between March 2003 and December 2010 were identified. Their electronic medical records were reviewed for allograft use, TBSA burned, injury severity score, anatomic distribution of burns, operative burden, length of stay, transfusions, and outcome. Among 844 patients, 112 (13.3%) received allograft and 732 (86.7%) did not. The amount of allograft used per patient varied and was not normally distributed (median, 23.5; interquartile range, 69.5). Patients received allograft skin an average of 12.75 times during their admission. Allografted patients sustained severe burns (µ, 53.8% TBSA); most were transfused (71.2%) and grafted frequently, averaging every 7.45 days. Most commonly, allograft was placed on the extremities (66.5%) followed by the trunk (44.2%); however, the vast majority of allografted patients also had concomitant burns of the head (91.1%) and hands (87.5%). All-cause mortality among the allografted patients was 19.1%. In conclusion, allograft is commonly used in the surgical treatment of severe burns. Although there are no anatomic limitations to allograft placement, there are distinct patterns of use. Given the role of allograft in the acute management of large burns, there is need for further investigation of its effect on mortality, morbidity, and antigenicity.

Characterization of mandibular fractures incurred from battle injuries in Iraq and Afghanistan from 2001-2010.

PURPOSE: The mandible is the most commonly fractured bone in the craniomaxillofacial skeleton among military casualties. The purpose of this study was to characterize the nature and severity of mandibular fractures incurred by US military personnel during combat. MATERIALS AND METHODS: We queried the Joint Theater Trauma Registry from October 2001 to April 2011 using all pertinent International Classification of Diseases, Ninth Revision codes to identify fractures of the mandible. Fractures were then classified based on type and location. Chart reviews were performed on the subset of patients who were treated at San Antonio Military Medical Center to further classify the anatomic pattern and treatment of these fractures. RESULTS: We identified 391 patients with mandibular fractures, of whom 45 were transferred to San Antonio Military Medical Center. Open fractures were seen in 75% of patients. Two or more fractures of the mandible were seen in 51% of patients. Comminuted fractures were present in 84%, and 31% had segmental losses. Eighty-six percent of fractures were operative; two-thirds of patients required a single surgical procedure, whereas the remaining one-third required multiple procedures. Forty-six percent of patients had pan-facial fractures. CONCLUSIONS: Mandibular fractures as a result of combat blast injuries were characterized by a high incidence of open, comminuted, multiple fractures. Associated facial fractures were common.

Characterization of midface fractures incurred in recent wars.

BACKGROUND: Facial injuries sustained by US military personnel during the wars in Iraq and Afghanistan have increased compared with past conflicts. Characterization of midface fractures (orbits, maxilla, zygoma, and nasal bones) sustained on the battlefield is needed to improve our understanding of these injuries, to optimize treatment, and to potentially direct strategic development of protective equipment in the future. METHODS: The military's Joint Theater Trauma Registry was queried for midface fractures from 2001 to 2011 using International Classification of Diseases, Ninth Revision diagnosis codes. Stratification was then performed, and individual treatment records from Brooke Army Medical Center were reviewed. Analysis of the fracture pattern, treatment, and complications was performed. RESULTS: One thousand seven hundred sixty individuals with midface fractures were identified. Those fractures sustained in battle were characterized by a predominance of open fractures, blast etiology, and associated injuries. Detailed record reviews of the patients treated at our institution revealed 45% of all midface fractures as operative. Thirty-one percent of these were treated at levels III and IV facilities outside the continental United States before arrival at our institution. Patients with midface fractures underwent multiple operations. There was a 30% rate of complication among operative fractures characterized by malalignment, implant exposure, and infection. Midface battle injuries also had a high incidence of orbital fractures and severe globe injuries. CONCLUSIONS: Midface fractures sustained in the battlefield have a high complication rate, likely as a result of the blast mechanism of injury with associated open fractures, multiple fractures, and associated injuries. These cases present unique challenges, often requiring both soft tissue and skeletal reconstruction.

Ten years of war: a characterization of craniomaxillofacial injuries incurred during operations Enduring Freedom and Iraqi Freedom.

BACKGROUND: Improved armor and battlefield medicine have led to better survival in the wars in Iraq and Afghanistan than any previous ones. Increased frequency and severity of craniomaxillofacial injuries have been proposed. A comprehensive characterization of the injury pattern sustained during this 10-year period to the craniomaxillofacial region is needed to improve our understanding of these unique injuries, to optimize the treatment for these patients, and to potentially direct strategic development of protective equipment in the future. METHODS: The Joint Theater Trauma Registry was queried from October 19, 2001, to March 27, 2011, covering operations Enduring Freedom and Iraqi Freedom for battle injuries to the craniomaxillofacial region, including patient demographics and mechanism of injury. Injuries were classified according to type (wounds, fractures, burns, vascular injuries, and nerve injuries) using DRG International Classification of Diseases-9th Rev. diagnosis codes. RESULTS: In this 10-year period, craniomaxillofacial battle injuries to the head and neck were found in 42.2% of patients evacuated out of theater. There is a high preponderance of multiple wounds and open fractures in this region. The primary mechanism of injury involved explosive devices, followed by ballistic trauma. CONCLUSION: Modern combat, characterized by blast injuries, results in higher than previously reported incidence of injury to the craniomaxillofacial region. LEVEL OF EVIDENCE: Epidemiologic study, level IV.

Injectable reactive biocomposites for bone healing in critical-size rabbit calvarial defects.

Craniofacial injuries can result from trauma, tumor ablation, or infection and may require multiple surgical revisions. To address the challenges associated with treating craniofacial bone defects, an ideal material should have the ability to fit complex defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the ability of injectable lysine-derived polyurethane (PUR)/allograft biocomposites to promote bone healing in critical-size rabbit calvarial defects. The biocomposites exhibited favorable injectability, characterized by a low yield stress to initiate flow of the material and a high initial viscosity to minimize the adverse phenomena of extravasation and filter pressing. After injection, the materials cured within 10-12 min to form a tough, elastomeric solid that maintained mechanical integrity during the healing process. When injected into a critical-size calvarial defect in rabbits, the biocomposites supported ingrowth of new bone. The addition of 80 µg mL(-1) recombinant human bone morphogenetic protein-2 (rhBMP-2) enhanced new bone formation in the interior of the defect, as well as bridging of the defect with new bone. These observations suggest that injectable reactive PUR/allograft biocomposites are a promising approach for healing calvarial defects by providing both mechanical stability as well as local delivery of rhBMP-2.

Executive summary: Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: endorsed by the Infectious Diseases Society of America and the Surgical Infection Society.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.

Guidelines for the prevention of infections associated with combat-related injuries: 2011 update: endorsed by the Infectious Diseases Society of America and the Surgical Infection Society.

Despite advances in resuscitation and surgical management of combat wounds, infection remains a concerning and potentially preventable complication of combat-related injuries. Interventions currently used to prevent these infections have not been either clearly defined or subjected to rigorous clinical trials. Current infection prevention measures and wound management practices are derived from retrospective review of wartime experiences, from civilian trauma data, and from in vitro and animal data. This update to the guidelines published in 2008 incorporates evidence that has become available since 2007. These guidelines focus on care provided within hours to days of injury, chiefly within the combat zone, to those combat-injured patients with open wounds or burns. New in this update are a consolidation of antimicrobial agent recommendations to a backbone of high-dose cefazolin with or without metronidazole for most postinjury indications, and recommendations for redosing of antimicrobial agents, for use of negative pressure wound therapy, and for oxygen supplementation in flight.