A Two-Stage Approach Integrating Provisional Biomaterial-Mediated Stabilization Followed by a Definitive Treatment for Managing Volumetric Muscle Loss Injuries.

Treatment of volumetric muscle loss (VML) faces challenges due to its unique pathobiology and lower priority in severe musculoskeletal injury management. Consequently, a need exists for multi-stage VML treatment strategies to accommodate delayed interventions owing to comorbidity management or prolonged casualty care in combat settings. To this end, polyvinyl alcohol (PVA) was used at concentrations of 5%, 7.

Exoskeletal solutions to enable mobility with a lower leg fracture in austere environments.

The treatment and evacuation of people with lower limb fractures in austere environments presents unique challenges that assistive exoskeletal devices could address. In these dangerous situations, independent mobility for the injured can preserve their vital capabilities so that they can safely evacuate and minimize the need for additional personnel to help. This expert view article discusses how different exoskeleton archetypes could provide independent mobility while satisfying the requisite needs for portability, maintainability, durability, and adaptability to be available and useful within austere environments.

Exploring relationships among multi-disciplinary assessments for knee joint health in service members with traumatic unilateral lower limb loss: a two-year longitudinal investigation.

Motivated by the complex and multifactorial etiologies of osteoarthritis, here we use a comprehensive approach evaluating knee joint health after unilateral lower limb loss. Thirty-eight male Service members with traumatic, unilateral lower limb loss (mean age = 38 yr) participated in a prospective, two-year longitudinal study comprehensively evaluating contralateral knee joint health (i.e.

Demographics and Comorbidities of United States Service Members with Combat-Related Lower Extremity Limb Salvage.

Introduction: This retrospective study describes the demographics and injury characteristics of a recently identified cohort of US Service members with combat-related lower extremity limb salvage (LS).

Methods: US Service members with combat trauma were identified from the Expeditionary Medical Encounter Database and Military Health System Data Repository and stratified into primary amputation (PA), LS, and non-threatened limb trauma (NTLT) cohorts based on ICD-9 codes. Disparities in demographic factors and injury characteristics were investigated across cohorts and within the LS cohort based on limb retention outcome.

In situ forming biomaterials as muscle void fillers for the provisional treatment of volumetric muscle loss injuries.

Volumetric muscle loss (VML) represents a devastating extremity injury which leads to chronic functional deficits and disability and is unrecoverable through normal healing pathways. When left untreated, the VML pathophysiology creates many challenges towards successful treatment, such as altered residual muscle architecture, excessive fibrosis, and contracture(s). As such, innovative approaches and technologies are needed to prevent or reverse these adverse sequelae.

Mobility Solutions After a Lower Extremity Fracture and Applicability to Battlefield and Wilderness Medicine.

The potential for delayed evacuation of injured Service members from austere environments highlights the need to develop solutions that can stabilize a wound and enable mobility during these prolonged casualty care (PCC) scenarios. Lower extremity fractures have traditionally been treated by immobilization (splinting) followed by air evacuation - a paradigm not practical in PCC scenarios. In the civilian sector, treatment of extremity injuries sustained during remote recreational activities have similar challenges, particularly when adverse weather or terrain precludes early ground or air rescue.

Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture.

Intra-articular fractures (IAF) result in significant and prolonged inflammation, increasing the chances of developing post-traumatic osteoarthritis (PTOA). Interleukin-one beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α) are key inflammatory factors shown to be involved in osteochondral degradation following IAF. As such, use of targeted biologics such as Infliximab (INX), a TNF-α inhibitor, and Anakinra (ANR), an interleukin-one (IL-1) receptor antagonist (IL1RA), may protect against PTOA by damping the inflammatory response to IAF and reducing osteochondral degradation.

Development and characterization of an intra-articular fracture mediated model of post-traumatic osteoarthritis.

Purpose: This study aimed to develop and characterize a closed intra-articular fracture (IAF) mediated post-traumatic osteoarthritis (PTOA) model in rats to serve as a testbed for putative disease modifying interventions.

Methods: Male rats were subject to a 0 Joule (J), 1 J, 3 J, or 5 J blunt-force impact to the lateral aspect of the knee and allowed to heal for 14 and 56 days. Micro-CT was performed at time of injury and at the specified endpoints to assess bone morphometry and bone mineral density measurements.

Minced muscle autografting improves bone healing but not muscle function in a porcine composite injury model.

Composite tissue injuries (CTIs) in extremities include segmental bone defects (SBDs) and volumetric muscle loss. The objective of this study was to determine if skeletal muscle autografting with minced muscle grafts (MMGs) could improve healing in an SBD and improve muscle function in a porcine CTI model that includes an SBD and adjacent volumetric muscle loss injury. Adult Yucatan Minipigs were stratified into three groups including specimens with an isolated SBD, an SBD with volumetric muscle loss (CTI), and an SBD with volumetric muscle loss treated with MMG (CTI + MMG).

Effects of Adjunct Antifibrotic Treatment within a Regenerative Rehabilitation Paradigm for Volumetric Muscle Loss.

The use of a rehabilitation approach that promotes regeneration has the potential to improve the efficacy of pro-regenerative therapies and maximize functional outcomes in the treatment of volumetric muscle loss (VML). An adjunct antifibrotic treatment could further enhance functional gains by reducing fibrotic scarring. This study aimed to evaluate the potential synergistic effects of losartan, an antifibrotic pharmaceutical, paired with a voluntary wheel running rehabilitation strategy to enhance a minced muscle graft (MMG) pro-regenerative therapy in a rodent model of VML.

Repurposing existing products to accelerate injury recovery (REPAIR) of military relevant musculoskeletal conditions.

Musculoskeletal injuries (MSKIs) are a great hindrance to the readiness of the United States Armed Forces through lost duty time and reduced operational capabilities. While most musculoskeletal injuries result in return-to-duty/activity with no (functional) limitations, the healing process is often long. Long healing times coupled with the high frequency of musculoskeletal injuries make them a primary cause of lost/limited duty days.

Volumetric Muscle Loss: A Bibliometric Analysis of a Decade of Progress.

The consequences of military conflict, accidents, and diseases have led to the definition-and subsequent study-of the pathological condition now known as volumetric muscle loss (VML). VML is a significant injury to skeletal muscle tissue on a scale that is endogenously irrecoverable and leads to chronic functional deficits and long-term disability. Currently, there lacks a definitive approach to meaningfully restore the tissue and function lost by those afflicted, ushering a need for scientific activities and associated funding to both facilitate a deeper understanding of the pathobiology of VML as well as to develop and assess clinically relevant therapeutics and treatment strategies.

The impact of bilateral injuries on the pathophysiology and functional outcomes of volumetric muscle loss.

Volumetric muscle loss (VML)-defined as the irrecoverable loss of skeletal muscle tissue with associated persistent functional deficits-is among the most common and highly debilitating combat-related extremity injuries. This is particularly true in cases of severe polytrauma wherein multiple extremities may be involved as a result of high energy wounding mechanisms. As such, significant investment and effort has been made toward developing a clinically viable intervention capable of restoring the form and function of the affected musculature.

Efficacy of non-surgical interventions for promoting improved functional outcomes following acute compartment syndrome: A systematic review.

Background: Acute compartment syndrome (ACS) is a devastating complication which develops following a traumatic extremity injury that results in increased pressure within osteofascial compartments, thereby leading to ischemia, muscle and nerve necrosis, and creates a life-threatening condition if left untreated. Fasciotomy is the only available standard surgical intervention for ACS. Following fasciotomy the affected extremity is plagued by prolonged impairments in function.

Retrospective characterization of a rat model of volumetric muscle loss.

Volumetric muscle loss (VML) is a pervasive injury within contemporary combat and a primary driver of disability among injured Service members. As such, VML has been a topic of investigation over the past decade as the field has sought to understand the pathology of these injuries and to develop treatment strategies which restore the form and function of the involved musculature. To date, much of this work has been performed in disparate animal models that vary significantly in terms of the species utilized, the muscle (or muscle group) affected, and the volume of muscle lost.

A Comprehensive, Multidisciplinary Assessment for Knee Osteoarthritis Following Traumatic Unilateral Lower Limb Loss in Service Members.

Introduction: Knee osteoarthritis (KOA) is a primary source of long-term disability and decreased quality of life (QoL) in service members (SM) with lower limb loss (LL); however, it remains difficult to preemptively identify and mitigate the progression of KOA and KOA-related symptoms. The objective of this study was to explore a comprehensive cross-sectional evaluation, at the baseline of a prospective study, for characterizing KOA in SM with traumatic LL.

Materials And Methods: Thirty-eight male SM with traumatic unilateral LL (23 transtibial and 15 transfemoral), 9.

Development of a High-Color Flow Cytometry Panel for Immunologic Analysis of Tissue Injury and Reconstruction in a Rat Model.

The rat model is an important resource in biomedical research due to its similarities to the human immune system and its use for functional studies. However, because of the preponderance of mouse models in foundational and mechanistic immunological studies, there is a relative lack of diverse, commercially available flow cytometry antibodies for immunological profiling in the rat model. Available antibodies are often conjugated to common fluorophores with similar peak emission wavelengths, making them hard to distinguish on conventional flow cytometers and restricting more comprehensive immune analysis.

The Role of the Inflammatory Response in Mediating Functional Recovery Following Composite Tissue Injuries.

Composite tissue injuries (CTI) are common among US Military Service members during combat operations, and carry a high potential of morbidity. Furthermore, CTI are often complicated due to an altered wound healing response, resulting in part from a dysregulation of the innate and adaptive immune responses. Unlike normal wound healing, in CTI, disruptions occur in innate immune responses, altering neutrophil functions, macrophage activation and polarization, further impacting the functions of T regulatory cells.

Evaluating the potential use of functional fibrosis to facilitate improved outcomes following volumetric muscle loss injury.

Volumetric muscle loss (VML) was defined as the frank loss of skeletal muscle tissue with associated chronic functional deficits. Significant effort has been dedicated to developing approaches for treating VML injuries, most of which have focused on stimulating regeneration of the affected musculature via a variety of approaches (e.g.

Evaluation of licofelone as an adjunct anti-inflammatory therapy to biologic scaffolds in the treatment of volumetric muscle loss.

Biologic scaffolds (BS) are the most widely studied therapeutics for the treatment of volumetric muscle loss (VML) owing to their purported effects on cell proliferation, chemotaxis, migration, and differentiation. Despite these claims, variability in reports on the nature of the immune response to their implantation suggests that BS-associated inflammation may be limiting their regenerative efficacy. To address this shortcoming, this study sought to evaluate licofelone (ML3000), a dual 5-LOX/COX inhibitor, as an anti-inflammatory adjunct therapy to a BS in the treatment of VML.

Prolonged field care for traumatic extremity injuries: defining a role for biologically focused technologies.

Extremity injuries occur frequently during warfare. While traditionally treated in definitive clinics, the future battlefield is projected to be different in a variety of ways, and there will likely be a shift towards prolonged field care (PFC) for treating extremity traumas. PFC is defined as field medical care that is applied beyond “doctrinal planning time-lines” by a tactical medical practitioner in order to decrease patient mortality and morbidity.

Gait biomechanics: A clinically relevant outcome measure for preclinical research of musculoskeletal trauma.

Traumatic injuries to the musculoskeletal system are the most prevalent of those suffered by United States Military Service members and accounts for two-thirds of initial hospital costs to the Department of Defense. These combat-related wounds often leave survivors with life-long disability and represent a significant impediment to the readiness of the fighting force. There are immense opportunities for the field of tissue engineering and regenerative medicine (TE/RM) to address these musculoskeletal injuries through regeneration of damaged tissues as a means to restore limb functionality and improve quality of life for affected individuals.

COX-2 inhibition does not alter wound healing outcomes of a volumetric muscle loss injury treated with a biologic scaffold.

Volumetric muscle loss (VML) injuries are characterized by a heightened immune response that alters canonical wound healing outcomes and results in a chronic reduction of both total myofiber number and functional capacity. Preclinical and clinical investigations aimed at repairing VML injuries have largely utilized biologic scaffolds (BSs) as a potential therapeutic intervention. BSs rely on the recruitment of a myriad of host-derived immune, stem, and stromal cells to induce a wound healing response that has been routinely characterized as largely fibrous matrix deposition and limited myofiber regeneration at the site of the defect.

Volumetric muscle loss disrupts length-dependent architectural and functional characteristics of skeletal muscle.

: Skeletal muscle architecture is a primary determinant of function. Volumetric muscle loss (VML) injury is destructive; however, the impact on muscle architecture is uncharacterized. : Architectural and functional effects of VML were assessed in rat tibialis anterior (TA) muscle model 4 weeks post-injury.