Determining Which Combinatorial Combat-Relevant Factors Contribute to Heterotopic Ossification Formation in an Ovine Model.

Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

The use of a computer-assisted rehabilitation environment (CAREN) for enhancing wounded warrior rehabilitation regimens.

PURPOSE: This paper seeks to describe how novel technologies such as the computer-assisted research environment (CAREN) may improve physical and cognitive rehabilitation for wounded warfighters. DESIGN/METHODOLOGY/APPROACH: The CAREN system is a dynamic platform which may assist service members who have sustained improvised explosive device injuries during Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn. The complex nature of warfighter injuries present unique rehabilitation challenges that demand new tools for quick return to active duty or the civilian community. FINDINGS: Virtual reality-based gait training programs may directly influence physiological and biomechanical performance for those who have endured combat injuries. The CAREN system provides a safe, interactive environment for the user while capturing kinematic and kinetic data capture to improve rehabilitation regimens. CONCLUSIONS: This paper provides an overview of the CAREN system and describes how this dynamic rehabilitation aid may be a translational tool for collecting biomechanical and physiological data during prosthetic training. The CAREN platform allows users to be fully immersed in a virtual environment while healthcare providers use these simulations to improve gait and stability, obstacle avoidance, or improved weight shifting. As such, rehabilitation regimens may be patient specific.

Comparison of Staphylococcus aureus tolerance between antimicrobial blue light, levofloxacin, and rifampin.

Background: Bacterial biofilms readily develop on all medical implants, including percutaneous osseointegrated (OI) implants. With the growing rate of antibiotic resistance, exploring alternative options for managing biofilm-related infections is necessary. Antimicrobial blue light (aBL) is a unique therapy that can potentially manage biofilm-related infections at the skin-implant interface of OI implants. Antibiotics are known to have antimicrobial efficacy disparities between the planktonic and biofilm bacterial phenotypes, but it is unknown if this characteristic also pertains to aBL. In response, we developed experiments to explore this aspect of aBL therapy. Methods: We determined minimum bactericidal concentrations (MBCs) and antibiofilm efficacies for aBL, levofloxacin, and rifampin against Staphylococcus aureus ATCC 6538 planktonic and biofilm bacteria. Using student t-tests (p < 0.05), we compared the efficacy profiles between the planktonic and biofilm states for the three independent treatments and a levofloxacin + rifampin combination. Additionally, we compared antimicrobial efficacy patterns for levofloxacin and aBL against biofilms as dosages increased. Results: aBL had the most significant efficacy disparity between the planktonic and biofilm phenotypes (a 2.5 log10 unit difference). However, further testing against biofilms revealed that aBL had a positive correlation between increasing efficacy and exposure time, while levofloxacin encountered a plateau. While aBL efficacy was affected the most by the biofilm phenotype, its antimicrobial efficacy did not reach a maximum. Discussion/conclusion: We determined that phenotype is an important characteristic to consider when determining aBL parameters for treating OI implant infections. Future research would benefit from expanding these findings against clinical S. aureus isolates and other bacterial strains, as well as the safety of long aBL exposures on human cells.

Comparison of prosthetic mobility and balance in transfemoral amputees with bone-anchored prosthesis vs. socket prosthesis.

BACKGROUND: The literature comparing bone-anchored prosthesis (BAP) with socket prosthesis (SP) consistently reports improvement in physical health and quality of life using primarily patient-reported outcome measures (PROMs). OBJECTIVE: To determine the differences in mobility and balance using performance-based outcome measures and PROMs in people with transfemoral amputations (TFAs) fitted with BAP vs. SP. STUDY DESIGN: Causal comparative. METHODS: Two groups of people with TFAs were recruited: one using a BAP (N = 11; mean age ± standard deviation, 44 ± 14.9 years; mean residual limb length as a percentage of the intact femur, 68% ± 15.9) and another group using a SP (N = 11; mean age ± standard deviation, 49.6 ± 16.0 years; mean residual limb length as a percentage of the intact femur, 81% ± 13.9), and completed the 10-meter walk test, component timed-up-and-go, Prosthetic Limb Users Survey of Mobility™ 12-item, and Activities-specific Balance Confidence Scale. RESULTS: There were no statistically significant differences between the BAP and SP groups in temporal spatial gait parameters and prosthetic mobility as measured by the 10-meter walk test and component timed-up-and-go, yet large effect sizes were found for several variables. In addition, Activities-specific Balance Confidence Scale and Prosthetic Limb Users Survey of Mobility™ scores were not statistically different between the BAP and SP groups, yet a large effect sizes were found for both variables. CONCLUSIONS: This study found that people with TFA who use a BAP can demonstrate similar temporal spatial gait parameters and prosthetic mobility, as well as self-perceived balance confidence and prosthetic mobility as SP users. Therefore, suggesting that the osseointegration reconstruction surgical procedure provides an alternative option for a specific population with TFA who cannot wear nor have limitations with a SP. Future research with a larger sample and other performance-based outcome measures and PROMs of prosthetic mobility and balance would further determine the differences between the prosthetic options.

Ex vivo comparison of V.A.C.® Granufoam Silver™ and V.A.C.® Granufoam™ loaded with a first-in-class bis-dialkylnorspermidine-terphenyl antibiofilm agent.

Implementation of negative pressure wound therapy (NPWT) as a standard of care has proven efficacious in reducing both the healing time and likelihood of nosocomial infection among pressure ulcers and traumatic, combat-related injuries. However, current formulations may not target or dramatically reduce bacterial biofilm burden following therapy. The purpose of this study was to determine the antibiofilm efficacy of an open-cell polyurethane (PU) foam (V.A.C.® Granufoam™) loaded with a first-in-class compound (CZ-01179) as the active release agent integrated via lyophilized hydrogel scaffolding. An ex vivo porcine excision wound model was designed to perform antibiofilm efficacy testing in the presence of NPWT. PU foam samples loaded with a 10.0% w/w formulation of CZ-01179 and 0.5% hyaluronic acid were prepared and tested against current standards of care: V.A.C.® Granufoam Silver™ and V.A.C.® Granufoam™. We observed statistically significant reduction of methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii biofilms with the CZ-01179 antibiofilm foam in comparison to current standard of care foams. These findings motivate further development of an antibiofilm PU foam loaded with CZ-01179.

Active Duty Service Members Newly Presenting With Low Back Pain in Fiscal Year 2017: Health Care Utilization, Access to Care, and Private Sector Costs Over 2-year Follow-up.

INTRODUCTION: Low back pain (LBP) has accounted for the most medical encounters every year for the past decade among Active Duty Service Members (ADSMs) of the U.S. Armed Forces. The objectives of this retrospective, descriptive study were to classify LBP by clinical category (Axial, Radicular, and Other) and duration (Acute, Subacute, and Chronic) and examine the LBP-related health care utilization, access to care, and private sector costs for ADSMs over a 2-year follow-up period. MATERIALS AND METHODS: The Military Health System Data Repository was queried in fiscal year 2017 for all ADSMs (ages 18-62) with outpatient encounters documented with any of 67 ICD-10 diagnosis codes indicative of LBP. A 1-year clean period before the first (index) outpatient LBP encounter date was used to ensure no recent history of LBP care. Patients were eligible if continuously enrolled and on active duty for 1 year before and 2 years following the index visit. Patients were excluded for non-musculoskeletal causes for LBP, red flags, or acute trauma within 4 weeks of the index visit and/or systemic illness or pregnancy anytime during the clean or follow-up period. RESULTS: A total of 52,118 ADSMs met the inclusion criteria, and the cohort was classified by duration of LBP symptoms as Acute [17,916 (34.4%)], Subacute [4,119 (7.9%)], and Chronic [30,083 (57.7%)]. Over 2-year follow-up, 419,983 outpatient visits were recorded, with the majority occurring at MTFs [363,570 (86.6%)]. 13,237 (25.4%) of ADSMs in the total cohort were documented with no other LBP-related visits beyond their index encounter. In contrast, the Chronic cohort comprised the highest number of encounters [371,031 (89.2% of total encounters)], including 86% of imaging studies performed for LBP, and accounted for $9,986,606.17 (94.9%) of total private sector costs over the 2-year follow-up period. Interventional pain procedures ($2,983,767.50) and physical therapy ($2,298,779.07) represented the costliest categories in the private sector for the Chronic cohort, whereas Emergency Department ($283,307.43) and physical therapy ($137,035.54) encounters were the top contributors to private sector costs for the Acute and Subacute cohorts, respectively. Overall reliance on the private sector was highest for specialty care, including 10,721 (75.4%) interventional pain procedures and 306 (66.4%) spine surgeries. CONCLUSIONS: Uncovering current trends in health care utilization and access to care for ADSMs newly presenting with LBP is vital for timely and accurate diagnosis, as well as early intervention to prevent progression to chronic LBP and to minimize its negative impact on military readiness and quality of life. This retrospective, descriptive study highlights the burden of chronic LBP on health care utilization and costs within the Military Health System, including reliance on the private sector care, amounting to $10,524,332.04 over the study period.

Antibiofilm potential of a negative pressure wound therapy foam loaded with a first-in-class tri-alkyl norspermidine-biaryl antibiotic.

Negative-pressure wound therapy (NPWT) is commonly utilized to treat traumatic injuries sustained on the modern battlefield. However, NPWT has failed to decrease the incidence of deep tissue infections experienced by Wounded Warriors, despite attempts to integrate common antimicrobials, like Ag+ nanoparticles, into the wound dressing. The purpose of this study was to incorporate a unique antibiofilm compound (CZ-01179) into the polyurethane matrix of NPWT foam via lyophilized hydrogel scaffolding. Foam samples with 2.5%, 5.0%, and 10.0% w/w CZ-01179 were produced and antibiofilm efficacy was compared to the current standards of care: V.A.C.® GRANUFOAM SILVER™ and V.A.C.® GRANUFOAM™. Gravimetric analysis and elution kinetics testing confirmed that this loading technique was both repeatable and controllable. Furthermore, zone of inhibition and antibiofilm efficacy testing showed that foam loaded with CZ-01179 had significantly increased activity against planktonic and biofilm phenotypes of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii compared to the clinical standards. These findings motivate additional ex vivo and in vivo work with NPWT foam loaded with CZ-01179 with the overall objective of reducing NPWT-associated infections that complicate battlefield-related and other wounds.

Clarifying the structure and bone mineral content of heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) has been reported as a pathologic process characterized by ectopic bone growth in muscle and/or periarticular regions. Previous reports have speculated that HO manifests as cancellous bone, cortical bone, or woven bone. Confusion regarding HO bone morphology has resulted from radiographic assessments and light microscopy, which lack the resolution required for accurately determining advanced bone architecture. Therefore, a more thorough histologic assessment using scanning electron microscopy (SEM) and backscatter electron (BSE) imaging was needed to improve HO characterization. MATERIALS AND METHODS: HO samples were collected from five adult trauma patients after surgical resection and examined with radiography, BSE, and histologic stains. RESULTS: BSE data demonstrated that HO was composed of a heterogeneous mixture of cortical and cancellous bone with distinct regions of fibrocartilage. Bone mineralization levels varied on a patient-specific basis, with the highest percentage of hypermineralization occurring in the oldest patient. BSE and histologic stains also indicated HO remodeling continued even after 3 y from injury to resection, as evident by osteoclastic resorption and osteoid deposition. CONCLUSIONS: BSE provided a more accurate understanding of HO bone mineralization and structure which may lead to improved surgical planning and treatment strategies for prevention of HO recurrence after resection.

Developing a combat-relevant translatable large animal model of heterotopic ossification.

Heterotopic ossification (HO) refers to ectopic bone formation, typically in residual limbs following trauma and injury. A review of injuries from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) indicated that approximately 70% of war wounds involved the musculoskeletal system, largely in part from the use of improvised explosive devices (IED) and rocket-propelled grenades (RPG). HO is reported to occur in approximately 63%-65% of wounded warriors from OIF and OEF. Symptomatic HO may delay rehabilitation regimens since it often requires modifications to prosthetic limb componentry and socket size. There is limited evidence indicating a mechanism for preventing HO. This may be due to inadequate models, which do not produce HO bone structure that is morphologically similar to HO samples obtained from wounded warfighters injured in theatre. We hypothesized that using a high-power blast of air (shockwave) and simulated battlefield trauma (i.e. bone damage, tourniquet, bacteria, negative pressure wound therapy) in a large animal model, HO would form and have similar morphology to ectopic bone observed in clinical samples. Initial radiographic and micro-computed tomography (CT) data demonstrated ectopic bone growth in sheep 24 weeks post-procedure. Advanced histological and backscatter electron (BSE) analyses showed that 5 out of 8 (63%) sheep produced HO with similar morphology to clinical samples. We conclude that not all ectopic bone observed by radiograph or micro-CT in animal models is HO. Advanced histological and BSE analyses may improve confirmation of HO presence and morphology, which we demonstrated can be produced in a large animal model.

A Randomized Feasibility Trial of a Novel, Integrative, and Intensive Virtual Rehabilitation Program for Service Members Post-Acquired Brain Injury.

INTRODUCTION: Acquired Brain Injury, whether resulting from Traumatic brain injury (TBI) or Cerebral Vascular Accident (CVA), represent major health concerns for the Department of Defense and the nation. TBI has been referred to as the "signature" injury of recent U.S. military conflicts in Iraq and Afghanistan - affecting approximately 380,000 service members from 2000 to 2017; whereas CVA has been estimated to effect 795,000 individuals each year in the United States. TBI and CVA often present with similar motor, cognitive, and emotional deficits; therefore the treatment interventions for both often overlap. The Defense Health Agency and Veterans Health Administration would benefit from enhanced rehabilitation solutions to treat deficits resulting from acquired brain injuries (ABI), including both TBI and CVA. The purpose of this study was to evaluate the feasibility of implementing a novel, integrative, and intensive virtual rehabilitation system for treating symptoms of ABI in an outpatient clinic. The secondary aim was to evaluate the system's clinical effectiveness. MATERIALS AND METHODS: Military healthcare beneficiaries with ABI diagnoses completed a 6-week randomized feasibility study of the BrightBrainer Virtual Rehabilitation (BBVR) system in an outpatient military hospital clinic. Twenty-six candidates were screened, consented and randomized, 21 of whom completed the study. The BBVR system is an experimental adjunct ABI therapy program which utilizes virtual reality and repetitive bilateral upper extremity training. Four self-report questionnaires measured participant and provider acceptance of the system. Seven clinical outcomes included the Fugl-Meyer Assessment of Upper Extremity, Box and Blocks Test, Jebsen-Taylor Hand Function Test, Automated Neuropsychological Assessment Metrics, Neurobehavioral Symptom Inventory, Quick Inventory of Depressive Symptomatology-Self-Report, and Post Traumatic Stress Disorder Checklist- Civilian Version. The statistical analyses used bootstrapping, non-parametric statistics, and multilevel/hierarchical modeling as appropriate. This research was approved by the Walter Reed National Military Medical Center and Uniformed Services University of the Health Sciences Institutional Review Boards. RESULTS: All of the participants and providers reported moderate to high levels of utility, ease of use and satisfaction with the BBVR system (x- = 73-86%). Adjunct therapy with the BBVR system trended towards statistical significance for the measure of cognitive function (ANAM [x- = -1.07, 95% CI -2.27 to 0.13, p = 0.074]); however, none of the other effects approached significance. CONCLUSION: This research provides evidence for the feasibility of implementing the BBVR system into an outpatient military setting for treatment of ABI symptoms. It is believed these data justify conducting a larger, randomized trial of the clinical effectiveness of the BBVR system.

In vivo efficacy of a unique first-in-class antibiofilm antibiotic for biofilm-related wound infections caused by Acinetobacter baumannii.

Wounds complicated by biofilms challenge even the best clinical care and can delay a return to duty for service members. A major component of treatment in wounded warriors includes infected wound management. Yet, all antibiotic therapy options have been optimized against planktonic bacteria, leaving an important gap in biofilm-related wound care. We tested the efficacy of a unique compound (CZ-01179) specifically synthesized to eradicate biofilms. CZ-01179 was formulated as the active agent in a hydrogel, and tested in vitro and in vivo in a pig excision wound model for its ability to treat and prevent biofilm-related wound infection caused by Acinetobacter baumannii. Data indicated that compared to a clinical standard-silver sulfadiazine-CZ-01179 was much more effective at eradicating biofilms of A. baumannii in vitro and up to 6 days faster at eradicating biofilms in vivo. CZ-01179 belongs to a broader class of newly-synthesized antibiofilm agents (referred to as CZ compounds) with reduced risk of resistance development, specific efficacy against biofilms, and promising formulation potential for clinical applications. Given its broad spectrum and biofilm-specific nature, CZ-01179 gel may be a promising agent to increase the pipeline of products to treat and prevent biofilm-related wound infections.

System Setup to Deliver Air Impact Forces to a Sheep Limb: Preparation for Model Development of Blast-Related Heterotopic Ossification.

BACKGROUND: Heterotopic ossification (HO) is a significant complication for wounded warriors with traumatic limb loss. Although this pathologic condition negatively impacts the general population, ectopic bone has been observed with higher frequency for service members injured in Iraq and Afghanistan due to blast injuries. Several factors, including a traumatic insult, bioburden, tourniquet and wound vacuum usage, and bone fractures or fragments have been associated with increased HO for service members. A large combat-relevant animal model is needed to further understand ectopic bone etiology and develop new pragmatic solutions for reducing HO formation and recurrence. OBJECTIVE: This study outlines the optimization of a blast system that may be used to simulate combat-relevant trauma for HO and replicate percussion blast experienced in theater. METHODS: We tested the repeatability and reproducibility of an air impact device (AID) at various pressure settings and compared it with a model of blunt force trauma for HO induction. Furthermore, we assessed the ability of the higher-power air delivery system to injure host tissue, displace metal particulate, and disperse bone chips in cadaveric sheep limbs. RESULTS: Data demonstrated that the air delivery setup generated battlefield-relevant blast forces. When the AID was charged to 40, 80, and 100 psi, the outputs were 229 (SD 13) N, 778 (SD 50) N, and 1085 (SD 114) N, respectively, compared with the blunt force model which proposed only 168 (SD 11) N. For the 100-psi AID setup, the force equaled a 5.8-kg charge weight of trinitrotoluene at a standoff distance of approximately 2.62 m, which would replicate a dismounted improvised explosive device blast in theater. Dispersion data showed that the delivery system would have the ability to cause host tissue trauma and effectively disperse metal particulate and host bone chips in local musculature compared with the standard blunt force model (13 mm vs 2 mm). CONCLUSIONS: Our data showed that a high-pressure AID was repeatable or reproducible, had the ability to function as a simulated battlefield blast that can model military HO scenarios, and will allow for factors including blast trauma to translate toward a large animal model.

Traumatic Brain Injury Incidence, Clinical Overview, and Policies in the US Military Health System Since 2000.

Exposure to explosive armaments during Operation Iraqi Freedom and Operation Enduring Freedom contributed to approximately 14% of the 352 612 traumatic brain injury (TBI) diagnoses in the US military between 2000 and 2016. The US Department of Defense issued guidelines in 2009 to (1) standardize TBI diagnostic criteria; (2) classify TBI according to mechanism and severity; (3) categorize TBI symptoms as somatic, psychological, or cognitive; and (4) systematize types of care given during the acute and rehabilitation stages of TBI treatment. Polytrauma and associated psychological and neurologic conditions may create barriers to optimal rehabilitation from TBI. Given the completion of recent combat operations and the transition of TBI patients into long-term care within the US Department of Veterans Affairs system, a review of the literature concerning TBI is timely. Long-term follow-up care for patients who have sustained TBI will remain a critical issue for the US military.

A Patient-Controlled Analgesia Adaptor to Mitigate Postsurgical Pain for Combat Casualties With Multiple Limb Amputation: A Case Series.

The use of explosive armaments during Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn has resulted in a significant number of injured U.S. service members. These weapons often generate substantial extremity trauma requiring multiple surgical procedures to preserve life, limb, and restore function. For those individuals who require multiple surgeries, the use of patient-controlled analgesia (PCA) devices can be an effective way to achieve adequate pain management and promote successful rehabilitation and recovery during inpatient treatment. A subpopulation of patients are unable to independently control a PCA device because of severe multiple limb dysfunction and/or loss. In response to the needs of these patients, our team designed and developed a custom adaptor to assist service members who would otherwise not be able to use a PCA. Patient feedback of the device indicated a positive response, improved independence, and overall satisfaction during inpatient hospitalization.

The Center for Rehabilitation Sciences Research: Advancing the Rehabilitative Care for Service Members With Complex Trauma.

The Center for Rehabilitation Sciences Research (CRSR) was established to advance the rehabilitative care for service members with combat-related injuries, particularly those with orthopedic, cognitive, and neurological complications. The center supports comprehensive research projects to optimize treatment strategies and promote the successful return to duty and community reintegration of injured service members. The center also provides a unique platform for fostering innovative research and incorporating clinical/technical advances in the rehabilitative care for service members. CRSR is composed of four research focus areas: (1) identifying barriers to successful rehabilitation and reintegration, (2) improving pain management strategies to promote full participation in rehabilitation programs, (3) applying novel technologies to advance rehabilitation methods and enhance outcome assessments, and (4) transferring new technology to improve functional capacity, independence, and quality of life. Each of these research focus areas works synergistically to influence the quality of life for injured service members. The purpose of this overview is to highlight the clinical research efforts of CRSR, namely how this organization engages a broad group of interdisciplinary investigators from medicine, biology, engineering, anthropology, and physiology to help solve clinically relevant problems for our service members, veterans, and their families.

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.

Establishing multiscale models for simulating whole limb estimates of electric fields for osseointegrated implants.

Although the survival rates of warfighters in recent conflicts are among the highest in military history, those who have sustained proximal limb amputations may present additional rehabilitation challenges. In some of these cases, traditional prosthetic limbs may not provide adequate function for service members returning to an active lifestyle. Osseointegration has emerged as an acknowledged treatment for those with limited residual limb length and those with skin issues associated with a socket together. Using this technology, direct skeletal attachment occurs between a transcutaneous osseointegrated implant (TOI) and the host bone, thereby eliminating the need for a socket. While reports from the first 100 patients with a TOI have been promising, some rehabilitation regimens require 12-18 months of restricted weight bearing to prevent overloading at the bone-implant interface. Electrically induced osseointegration has been proposed as an option for expediting periprosthetic fixation and preliminary studies have demonstrated the feasibility of adapting the TOI into a functional cathode. To assure safe and effective electric fields that are conducive for osseoinduction and osseointegration, we have developed multiscale modeling approaches to simulate the expected electric metrics at the bone-implant interface. We have used computed tomography scans and volume segmentation tools to create anatomically accurate models that clearly distinguish tissue parameters and serve as the basis for finite element analysis. This translational computational biological process has supported biomedical electrode design, implant placement, and experiments to date have demonstrated the clinical feasibility of electrically induced osseointegration.

Bone bioelectricity: what have we learned in the past 160 years?

The direct relationship between bone strain and electric fields has spurred continual interest in the field of bioelectricity over the past 160 years. It has been reported that stress-generated potentials alter cell proliferation and extracellular matrix secretion. The observation that endogenous electrical signals facilitate osteoinduction has lead to high production of electrical stimulation devices to fix bone defects. Despite the reported 100,000 nonunions healed as of 1990 with electrical stimulation, skepticism due to lack of homogeneity with trial design and dosage still exists within the scientific community. It is the purpose of this review to assess the bioelectric phenomenon of bone as it applies to piezoelectricity, fracture healing, and overall changes in bone metabolism which occur with controlled electrical stimulation.

The road to recovery and rehabilitation for injured service members with limb loss: a focus on Iraq and Afghanistan.

Amputation of an extremity due to traumatic injury or a vascular occlusive disease is a life-altering event that occurs when limb salvage is not possible. While an amputation is viewed as a life saving procedure clinically, limb deficiency may result in an immediate loss in social, physical and financial well-being for the patient. Military personnel returning from Operation Enduring Freedom and Operation Iraqi Freedom face unique challenges due to short residual limbs, unplanned amputations, high incidences of multiple limb loss, and accustomed activity levels prior to an amputation. The primary rehabilitation goal for these individuals is to provide them with an expedited recovery and progressive reintroduction into the civilian or active duty population. It is the purpose of this review to discuss the most frequent rehabilitation hardships service members endure following combat related trauma and future of prosthetic limb technology.

Developing a quantitative measurement system for assessing heterotopic ossification and monitoring the bioelectric metrics from electrically induced osseointegration in the residual limb of service members.

Poor prosthetic fit is often the result of heterotopic ossification (HO), a frequent problem following blast injuries for returning service members. Osseointegration technology offers an advantage for individuals with significant HO and poor socket tolerance by using direct skeletal attachment of a prosthesis to the distal residual limb, but remains limited due to prolonged post-operative rehabilitation regimens. Therefore, electrical stimulation has been proposed as a catalyst for expediting skeletal attachment and the bioelectric effects of HO were evaluated using finite element analysis in 11 servicemen with transfemoral amputations. Retrospective computed tomography (CT) scans provided accurate reconstructions, and volume conductor models demonstrated the variability in residual limb anatomy and necessity for patient-specific modeling to characterize electrical field variance if patients were to undergo a theoretical osseointegration of a prosthesis. In this investigation, the volume of HO was statistically significant when selecting the optimal potential difference for enhanced skeletal fixation, since higher HO volumes required increased voltages at the periprosthetic bone (p = 0.024, r = 0.670). Results from Spearman's rho correlations also indicated that the age of the subject and volume of HO were statistically significant and inversely proportional, in which younger service members had a higher frequency of HO (p = 0.041, r = -0.622). This study demonstrates that the volume of HO and age may affect the voltage threshold necessary to improve current osseointegration procedures.