Brad M. Isaacson

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.

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.

Bioelectric Analyses of an Osseointegrated Intelligent Implant Design System for Amputees

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.

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

Abstract Purpose This paper seeks to describe how novel technologies such as the computer-assisted rehabilitation 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.

Effectiveness of resonance frequency in predicting orthopedic implant strength and stability in an in vitro osseointegration model

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).

Tourniquet use in combat-injured service members: a link with heterotopic ossification?

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Orthopedic Research and Reviews 2014:6 27–31 Orthopedic Research and Reviews Dovepress

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.

Relationship between volumetric measurements of heterotopic ossification in wounded service members and clinically available screening tools

ABSTRACT 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. However, no studies to date have investigated the relationship of these clinical predictors with HO incidence and volume. Ten servicemen with transfemoral amputations were included in this retrospective study. Volumetric measurements of HO were calculated using thresholding software, and computed tomography scans were performed 12.6 ± 6.8 months after injury. Subject AP levels, white blood cell (WBC) counts, and pain scores were assessed to determine if these factors were predictors of ectopic bone volumes. The mean volume of HO was 44.73 ± 39.35 cm3. Statistical analysis demonstrated that the volume of HO and serum AP levels were significantly correlated (p = 0.002). However, average pain scores were not a significant predictor of HO volume (p = 0.212). Infections developed in 9 of the 10 subjects, and WBC counts and HO volumes were significantly correlated (p = 0.028). The magnitude of serum AP levels and WBC counts may be effective factors for predicting the expected volume of ectopic bone in combat-injured service members with transfemoral amputations.

Case Series of Wounded Warriors Receiving Initial Fit PowerKnee™ Prosthesis

Introduction Combat-related lower-limb amputations challenge prosthetic device prescription and rehabilitation practices. Moreover, wounded warriors are relatively young and lived highly active lifestyles before injury, underscoring their eagerness to quickly regain independent mobility and higher levels of physical function. Methods Four US military service members with combat-related unilateral amputation were fit with the PowerKnee™ as their initial prosthesis. Results All patients achieved significant mobility milestones more rapidly than historical norms of similarly injured patients using other prosthetic knees. Level-ground gait analysis of each patient was comparable with historical normative data of patients using advanced microprocessor variable dampening knee (MPK) prostheses, although the PowerKnee users generated less power in their intact limb hip and knee, suggesting less strain on intact joints. Each patient was also subsequently fit with an MPK and offered a hydraulic knee prosthesis for higher-level activities. Two of the four patients ultimately chose an alternative prosthesis as their primary knee, citing weight, ability to run, and battery life as key determinants. All patients, however, perceived the PowerKnee prosthesis to be valuable during their rehabilitation. Conclusion: The PowerKnee may be a viable option for the initial prosthetic fitting of individuals with transfemoral amputation. Further research is necessary to better understand the advantages or disadvantages of powered prosthetic technology, including their biomechanical effects on intact limbs, especially for high-level activities, and their ability to enhance early rehabilitation and optimal patient selection and timing of fitting.

Poster 42: Assessing the Feasibility of a Novel Non-Invasive Muscle Oxygenation Sensor for Guiding Wounded Warrior Rehabilitation: An Observational Study

Objective: The role of the cerebrovascular network and its acute response to traumatic brain injury (TBI) is poorly defined and emerging evidence suggests that cerebrovascular reactivity is altered. We explored how cortical vessels are physically altered from 1 to 30 days post injury (dpi) following TBI using a newly developed technique, vessel painting. Design: We tested our hypothesis that a focal moderate TBI results in decrements to structural aspects of the vasculature, followed by restoration and maturation of new vessels at the impact site. Rats underwent a moderate controlled cortical impact and were compared to sham operated animals. Animals underwent vessel painting perfusion to label the entire cerebral vasculature at 1, 3, 7, 14, and 30 dpi followed by whole brain axial and coronal imaging using a wide-field fluorescence microscope. Setting: Not applicable Participants: Not applicable Interventions: Not applicable Main Outcome Measures: Not applicable Results: Cortical vessel network characteristics were analyzed for classical angiographic features (junctions, density, lengths) of axial images wherein we observed significant (P < .05) reductions in vessel junctions and vessel density of the injured hemisphere at 1 and 3 dpi. Biological complexity can be quantified using fractal geometric features where we observed that fractal measures (kurtosis, skewness) were also reduced significantly (P < .05) in the early time points with evidence of vessel proliferation and maturation at later time points. Similar findings are noted on coronal imaging and analysis. Conclusions: Acutely after TBI there is a reduction in vascular network and vascular complexity, followed by proliferation and maturation of vasculature at the impact site. These findings provide structural evidence for the hemodynamic alterations that have been reported in rodents and patients after TBI. Level of Evidence: Level I