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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.

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.

Introduction Telehealth is an increasingly common approach to improve healthcare delivery, especially within the Veterans Health Administration and Department of Defense (DoD). Telehealth has diminished many challenges to direct access for clinical follow-up; however, the use of mobile telehealth for specialty rehabilitative care is emerging and is referred to as telerehabilitation. As early adopters of telehealth, the Veterans Affairs and DoD have supported collaborated efforts for programs designed to increase the access and quality of rehabilitative care while improving the functional ability of our service members (SMs) and veterans with lower limb amputation (LLA). The DoD and Veterans Health Administration collaborated on a Mobile Device Outcomes-based Rehabilitation Program (MDORP) to help injured SMs and veterans with LLA. The MDORP project utilized a mobile health system called the Rehabilitative Lower Limb Orthopedic Accommodating Device (ReLOAD) to assess walking quality. The ReLOAD system includes real-time auditory biofeedback to notify the user of their most prominent gait deviation and then recommends exercises that address specific balance and strength impairments. The purpose of this study was to describe the responses to a postintervention survey evaluating the feasibility and usability of ReLOAD completed by SMs and veterans with LLA who used the system for 5 months. Materials and Methods A link to an anonymous usability survey was emailed to all participants who completed MDORP. The survey was modeled after the System Usability Scale, with agreeableness to items rated on a 5-point Likert-style questionnaire in addition to open feedback. Data visualization of Likert-style questionnaires was conducted using ggplot2 and reshape2 statistical packages and was analyzed using R. We obtained institutional review board approval through both Miami Veterans Affairs Healthcare System and Walter Reed National Military Medical Center. Results The majority of participants reported that they would use the system again for home rehabilitation (65%) and that auditory biofeedback helped them walk better (59%). Participants also suggested that future work should include a greater variety of exercise options and the use of smart phones for the ReLOAD application in addition to the iPad tablet. Conclusions The participants provided positive and constructive feedback that will enhance the value and usability of telerehabilitation interventions like the ReLOAD system for future users.

Sexuality and intimacy are important aspects of life that are frequently compromised after severe injury or illness, yet these aspects are often overlooked by medical and rehabilitation professionals. This case series describes the Occupational Therapy Sexuality and Intimacy program at a Military Treatment Facility (MTF). Three diverse clients with a range of physical, cognitive and emotional impairments were chosen to illustrate complexities of the Occupational Therapy Sexuality and Intimacy Program at this MTF, and unique skills employed by Occupational Therapists. Consistent themes discovered include: perceived value of the program; appreciation of safe spaces to discuss personal topics; and enhanced awareness of role identity, body image, and emotional regulation. These cases illustrate that sexuality and intimacy interventions may have profound effects on injured service members, improving social reintegration, and quality of life.

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., Graphical abstract Unlabelled Image

Introduction The objective was to determine if the Mobile Device Outcomes-based Rehabilitation Program (MDORP) improved strength, mobility, and gait quality in service members (SMs) and Veterans with lower limb amputation (LLA). Methods Seven SMs and 10 Veterans with LLA enrolled and were trained to use a mobile sensor system, called Rehabilitative Lower Limb Orthopedic Analysis Device (ReLOAD). ReLOAD provided participants with real-time assessment of gait deviations, subsequent corrective audio feedback, and exercise prescription for normalizing gait at home and in the community. After baseline testing, prosthetic gait and exercise training, participants took ReLOAD home and completed an 8-week walking and home exercise program. Home visits were conducted every 2 weeks to review gait training and home exercises. Results Significant improvements in hip extensor strength, basic and high-level mobility, musculoskeletal endurance, and gait quality (P Conclusion Preliminary MDORP results are promising in its ability to improve basic and high-level mobility, lower limb strength, and gait quality in a group of SMs and Veterans with LLA. In addition, “booster” prosthetic training may be justified in an effort helps maintain an active lifestyle, promotes prosthetic use, and mitigates secondary health effects.

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 (x̄ = 73–86%). Adjunct therapy with the BBVR system trended towards statistical significance for the measure of cognitive function (ANAM [x̄ = −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.

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.

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.

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.

Over the past 200 years, there has been significant advancements in the fields of bioengineering and orthopaedics. Investigators, clinicians and manufactures are learning that the success of implant systems is not limited to a single factor, but a combination of variables that must work in unison to provide stability and high survivorship. Innovations continue to advance these fields and include: biomimetic alterations, three-dimensional, patient-specific reconstructions and novel coatings to mitigate aseptic loosening or other pathologies. However, implant systems continue to fail in clinical practice since they do not adhere to key fundamental principles. Therefore, this article is intended to highlight 5 hallmarks of biomaterials that should be considered during design, surgery, and post-operative rehabilitation.

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.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.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.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.

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.

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.

Heterotopic ossification (HO) often causes symptoms requiring surgical resection and may delay rehabilitation regimens for wounded service members. Clinical screening tools for assessing HO have included serum alkaline phosphatase (AP), nuclear scintigraphic activity, and patient pain scores

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.

Brad M Isaacson,1,2 Thomas M Swanson,1,2,4 Benjamin K Potter,4 Paul F Pasquina2,3 1The Henry M Jackson Foundation for the Advancement of Military Medicine, 2The Center for Rehabilitation Sciences Research, Department of Physical Medicine and Rehabilitation, Uniformed Services University of Health Sciences, 3Department of Rehabilitation, Walter Reed National Military Medical Center, 4Department of Orthopaedics, Walter Reed National Military Medical Center, Bethesda, Maryland, USA Abstract: Tourniquet use during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has contributed to the high survival rate of combat-injured service members. While preservation of a life – even at the potential expense of a limb – should always take precedence, delayed perfusion in traumatized residual limbs may alter the proliferation, differentiation, and function of endothelial and osteoprogenitor cells. Given the synergistic relationship between angiogenesis and osteogenesis, and the influence of environmental conditions on bone formation, hypoxic conditions from tourniquets may in part explain the higher frequency of heterotopic ossification (HO) present during OIF/OEF. Determining a correlation between tourniquet usage/duration on subsequent HO formation remains challenging. Long-term retrospective investigations have been limited, since the United States Army's Institute of Surgical Research did not standardized tourniquet issuance until July 2004. Thus, associating tourniquet-induced HO in previous military conflicts is not feasible, since poor medical documentation and inadequate application of these medical devices prevent large-scale meta-analyses. Therefore, this article focuses on the basics of bone biology and how tourniquet usage following combat trauma may impact osteogenesis, and subsequently, ectopic bone formation. Keywords: heterotopic ossification, osteogenesis, combat, trauma, ectopic bone, osteoprogenitor cells, Operation Iraqi Freedom, Operation Enduring Freedom

Our team completed the study and the PI published/submitted 8 manuscripts and 4 abstracts during the period of performance. Our final paper of 33 service members demonstrated that the MAR of trauma-induced HO was approximately 1.7 m/day at the time of surgical intervention, a value I .7x higher than non-pathological human bone. The MAR and post-operative alkaline phosphatase (AP) values and AP pre-operative levels and the percent of osteoblastic activity were positively related and statistically significant (p0.509, p0.026, n J 9) and(p0.522, p 0.004, n29) respectively. When data was analyzed only with in a two-year period from injury to excision (thereby removing outliers that were significantly longer than counterparts) and traumatic brain injury and non-steroidal anti inflammatory drugs were controlled for in the statistical analysis (known correlates with HO development), MAR and recurrence severity were significantly related(p-0.572, p0.041 , n J t ). Data from this grant showed a link between bench top research and bedside care, and demonstrates that the MAR is elevated in HO and correlated with recurrence risk; however, a larger sample size and more clinical factors are needed to refine this model. A follow-up HO grant awarded using this data as a benchmark for developing a translatable animal model (CDMRP-MRMC).

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.

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.

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.

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.

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 projected number of American amputees is expected to rise to 3.6 million by 2050. Many of these individuals depend on artificial limbs to perform routine activities, but prosthetic suspensions using traditional socket technology can prove to be cumbersome and uncomfortable for a person with limb loss. Moreover, for those with high proximal amputations, limited residual limb length may prevent exoprosthesis attachment all together. Osseointegrated implant technology is a novel operative procedure which allows firm skeletal attachment between the host bone and an implant. Preliminary results in European amputees with osseointegrated implants have shown improved clinical outcomes by allowing direct transfer of loads to the bone-implant interface. Despite the apparent advantages of osseointegration over socket technology, the current rehabilitation procedures require long periods of restrictive load bearing prior which may be reduced with expedited skeletal attachment via electrical stimulation. The goal of the osseointegrated intelligent implant design (OIID) system is to make the implant part of an electrical system to accelerate skeletal attachment and help prevent periprosthetic infection. To determine optimal electrode size and placement, we initiated proof of concept with computational modeling of the electric fields and current densities that arise during electrical stimulation of amputee residual limbs. In order to provide insure patient safety, subjects with retrospective computed tomography scans were selected and three dimensional reconstructions were created using customized software programs to ensure anatomical accuracy (Seg3D and SCIRun) in an IRB and HIPAA approved study. These software packages supported the development of patient specific models and allowed for interactive manipulation of electrode position and size. Preliminary results indicate that electric fields and current densities can be generated at the implant interface to achieve the homogenous electric field distributions required to induce osteoblast migration, enhance skeletal fixation and may help prevent periprosthetic infections. Based on the electrode configurations experimented with in the model, an external two band configuration will be advocated in the future.

Direct skeletal fixation, termed osseointegration, has expanded in the last century and includes use in total joint replacements, the edentulous mandible and maxilla, and percu- taneous osseointegrated prosthetics. Although it is well known that titanium and bone have the ability to form a durable bone-implant interface, new applications have emerged in the field of orthopedics, which requires a more thorough assessment of the literature. This review aims to introduce the basic biological principles for attaining osseointegration and discusses the major factors for assuring successful cementless fixation.

Developing noninvasive tools that determine implant attachment strength to bone and monitor implant stability over time will be important to optimize rehabilitation protocols following insertion of osseointegrated implants in patients with limb loss. While resonance frequency has been previously shown to correlate with implant stability in dental implants placed in the mandible and maxilla, this tool has not been evaluated with implants placed in the medullary canal of long bones. In an in vitro model used to simulate irregular medullary canal implant contact and osseointegration, a strong positive correlation was determined between resonance frequency implant stability quotient values and the force required for implant pushout. The force required for implant displacement also correlated to the distance from the point of fixation to the transducer at the proximal end of the implant (point of resonance frequency monitoring).