Remotely Controlled Electrochemical Degradation of Metallic Implants.

Biodegradable medical implants promise to benefit patients by eliminating risks and discomfort associated with permanent implantation or surgical removal. The time until full resorption is largely determined by the implant's material composition, geometric design, and surface properties. Implants with a fixed residence time, however, cannot account for the needs of individual patients, thereby imposing limits on personalization. Here, an active Fe-based implant system is reported whose biodegradation is controlled remotely and in situ. This is achieved by incorporating a galvanic cell within the implant. An external and wireless signal is used to activate the on-board electronic circuit that controls the corrosion current between the implant body and an integrated counter electrode. This configuration leads to the accelerated degradation of the implant and allows to harvest electrochemical energy that is naturally released by corrosion. In this study, the electrochemical properties of the Fe-30Mn-1C/Pt galvanic cell model system is first investigated and high-resolution X-ray microcomputed tomography is used to evaluate the galvanic degradation of stent structures. Subsequently, a centimeter-sized active implant prototype is assembled with conventional electronic components and the remotely controlled corrosion is tested in vitro. Furthermore, strategies toward the miniaturization and full biodegradability of this system are presented.

Inherent Antibacterial Properties of Biodegradable FeMnC(Cu) Alloys for Implant Application.

Implant-related infections or inflammation are one of the main reasons for implant failure. Therefore, different concepts for prevention are needed, which strongly promote the development and validation of improved material designs. Besides modifying the implant surface by, for example, antibacterial coatings (also implying drugs) for deterring or eliminating harmful bacteria, it is a highly promising strategy to prevent such implant infections by antibacterial substrate materials. In this work, the inherent antibacterial behavior of the as-cast biodegradable Fe69Mn30C1 (FeMnC) alloy against Gram-negative Pseudomonas aeruginosa and Escherichia coli as well as Gram-positive Staphylococcus aureus is presented for the first time in comparison to the clinically applied, corrosion-resistant AISI 316L stainless steel. In the second step, 3.5 wt % Cu was added to the FeMnC reference alloy, and the microbial corrosion as well as the proliferation of the investigated bacterial strains is further strongly influenced. This leads for instance to enhanced antibacterial activity of the Cu-modified FeMnC-based alloy against the very aggressive, wild-type bacteria P. aeruginosa. For clarification of the bacterial test results, additional analyses were applied regarding the microstructure and elemental distribution as well as the initial corrosion behavior of the alloys. This was electrochemically investigated by a potentiodynamic polarization test. The initial degraded surface after immersion were analyzed by glow discharge optical emission spectrometry and transmission electron microscopy combined with energy-dispersive X-ray analysis, revealing an increase of degradation due to Cu alloying. Due to their antibacterial behavior, both investigated FeMnC-based alloys in this study are attractive as a temporary implant material.

Cell-Material Interactions in Direct Contact Culture of Endothelial Cells on Biodegradable Iron-Based Stents Fabricated by Laser Powder Bed Fusion and Impact of Ion Release.

Additive manufacturing is a promising technology for the fabrication of customized implants with complex geometry. The objective of this study was to investigate the initial cell-material interaction of degradable Fe-30Mn-1C-0.02S stent structures in comparison to conventional 316L as a reference, both processed by laser powder bed fusion. FeMn-based alloys have comparable mechanical properties with clinically applied AISI 316L for a corrosion-resistant stent material. Different corrosion stages of the as-built Fe-30Mn-1C-0.02S stent surfaces were simulated by pre-conditioning in DMEM under cell culture conditions for 2 h, 7 days, and 28 days. Human umbilical vein endothelial cells (HUVECs) were directly seeded onto the pre-conditioned samples, and cell viability, adherence, and morphology were analyzed. These studies were accompanied by measurements of iron and manganese ion release and Auger electron spectroscopy to evaluate the influence of corrosion products and degradation on the cells. In the initial phase (2 h of pre-conditioning), HUVECs were able to attach but the cell number decreased over the cultivation period of 14 days and the CD31 staining pattern of intercellular contacts was disordered. At later time points of corrosion (7 and 28 days of pre-conditioning), CD31 staining was distinctly located at the intercellular contacts, and the cell density increased after seeding and was stable for up to 14 days. Formation of a complex degradation layer, which had a composition and thickness dependent on the pre-conditioning time, led to a reduced ion release and finally showed a positive effect on cell survival. Concluding, our data suggest the suitability of Fe-30Mn-1C-0.02S for in vivo applications.

In-depth analysis of life values and their corresponding inhibitors and facilitators in chronic low back pain patients: A mixed-method approach.

BACKGROUND: The struggle with pain often interferes with the ability of chronic low back pain (CLBP) patients to pursue important life values due to psychological inflexibility. OBJECTIVE: This research examined life values, related inhibitors and facilitators relevant to personalized therapy planning. METHODS: Two hundred and forty-four CLBP patients completed the Chronic Pain Values Inventory (CPVI). Of these, 68 patients were interviewed to assess inhibitors and facilitators related to life values. Mixed-effects models quantitatively examined differences in the values, structuring content analysis served to qualitatively analyze the interviews. RESULTS: Participants rated the value "family" as being of highest importance and success. The largest discrepancy between importance and success was found for "health". Content analyses revealed a broad range of inhibitors and facilitators related to the examined life values with the highest number of inhibitors related to "work". Facilitators were also found to be of relevance to all life values, but to a lower extent than inhibitors. CONCLUSIONS: The perceived importance and success of life values and their related inhibitors and facilitators may differentially affect CLBP patients. Considering such individual aspects is therefore of utmost importance to improve patient care, as they enable treatment goals and the therapeutic strategies to be adapted accordingly.

The impact of age and gender on the ICF-based assessment of chronic low back pain.

PURPOSE: To evaluate the impact of age and gender on the international classification of functioning, disability and health (ICF)-based assessment for chronic low back pain. METHODS: Two hundred forty-four chronic low back pain patients (52% female) with a mean age of 49 years (SD =17.64) were interviewed with the comprehensive ICF core set for activities and participation, and environmental factors. After conducting explorative factor analysis, the impact of age and gender on the different factors was analyzed using analyzes of variances. RESULTS: Results revealed that older patients experienced more limitations within "self-care and mobility" and "walking" but less problems with "transportation" compared to younger patients. Older or middle-aged low back pain patients further perceived more facilitation through "architecture and products for communication", "health services", and "social services and products for mobility" than younger patients. Regarding gender differences, women reported more restriction in "housework" than men. An interaction effect between age and gender was found for "social activities and recreation" with young male patients reporting the highest impairment. CONCLUSIONS: The study demonstrated that the comprehensive ICF core set classification for chronic low back pain is influenced by age and gender. This impact is relevant for ICF-based assessments in clinical practice, and should be considered in intervention planning for rehabilitative programs. Implications for rehabilitation It is important to consider age and gender differences when classifying with the ICF. The intervention planning based on the ICF should focus on improvement of bodily functioning and mobility in older patients, facilitation of household activities in women, consideration of work-life balance and recreation (e.g., through mindfulness based stress reduction), and reduction of dissatisfaction with rehabilitation in younger patients. It is important to offer patients the opportunity to participate in intervention planning based on the ICF. For intervention planning professionals should bear in mind the resource-oriented approach of the ICF (e.g., facilitation through environmental factors), and a collaboration with other professionals.

Biphasic Scaffolds from Marine Collagens for Regeneration of Osteochondral Defects.

BACKGROUND: Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable setup for in vitro chondrogenic and osteogenic differentiation of human mesenchymal stroma cells (hMSC). METHODS: Biphasic scaffolds from biomimetically mineralized salmon collagen and fibrillized jellyfish collagen were fabricated by joint freeze-drying and crosslinking. Different experiments were performed to analyze the influence of cell density and TGF-ß on osteogenic differentiation of the cells in the scaffolds. Gene expression analysis and analysis of cartilage extracellular matrix components were performed and activity of alkaline phosphatase was determined. Furthermore, histological sections of differentiated cells in the biphasic scaffolds were analyzed. RESULTS: Stable biphasic scaffolds from two different marine collagens were prepared. An in vitro setup for osteochondral differentiation was developed involving (1) different seeding densities in the phases; (2) additional application of alginate hydrogel in the chondral part; (3) pre-differentiation and sequential seeding of the scaffolds and (4) osteochondral medium. Spatially separated osteogenic and chondrogenic differentiation of hMSC was achieved in this setup, while osteochondral medium in combination with the biphasic scaffolds alone was not sufficient to reach this ambition. CONCLUSIONS: Biphasic, but monolithic scaffolds from exclusively marine collagens are suitable for the development of osteochondral constructs.

Three-dimensional plotting of a cell-laden alginate/methylcellulose blend: towards biofabrication of tissue engineering constructs with clinically relevant dimensions.

Biofabrication of tissue engineering constructs with tailored architecture and organized cell placement using rapid prototyping technologies is a major research focus in the field of regenerative therapies. This study describes a novel alginate-based material suitable for both cell embedding and fabrication of three-dimensional (3D) structures with predefined geometry by 3D plotting. The favourable printing properties of the material were achieved by using a simple strategy: addition of methylcellulose (MC) to a 3% alginate solution resulted in a strongly enhanced viscosity, which enabled accurate and easy deposition without high technical efforts. After scaffold plotting, the alginate chains were crosslinked with Ca2+ ; MC did not contribute to the gelation and was released from the scaffolds during the following cultivation. The resulting constructs are characterized by high elasticity and stability, as well as an enhanced microporosity caused by the transient presence of MC. The suitability of the alginate/MC blend for cell embedding was evaluated by direct incorporation of mesenchymal stem cells during scaffold fabrication. The embedded cells showed high viability after 3 weeks of cultivation, which was similar to those of cells within pure alginate scaffolds which served as control. Maintenance of the differentiation potential of embedded cells, as an important requirement for the generation of functional tissue engineering constructs, was proven for adipogenic differentiation as a model for soft tissue formation. In conclusion, the temporary integration of MC into a low-concentrated alginate solution allowed the generation of scaffolds with dimensions in the range of centimetres without loss of the positive properties of low-concentrated alginate hydrogels with regard to cell embedding. Copyright © 2015 John Wiley & Sons, Ltd.

Age-related test-retest reliability of isometric trunk torque measurements in patiens with chronic low back pain.

OBJECTIVE: To investigate the short- and long-term reliability of isometric trunk strength measurements in patients with chronic low back pain in different age groups. DESIGN: Test-retest reliability study. PATIENTS: A total of 210 patients (age groups 18-39, 40-59 and 60-90 years). METHODS: Patients performed testing at baseline, 1-2 days (day 2) and 6 weeks. RESULTS: Only the oldest age group showed similar extension strength on all three test days All age groups showed significant changes in rotation and flexion scores from baseline to 6 weeks. Younger age groups (18-39 and 40-59 years) showed significant increases in extension, flexion, and rotation strength at both short-term (baseline to day 2) and long-term (baseline to 6 weeks) retests, but not from day 2 to 6 weeks. In patients over 60 years of age the smallest real differences normalized to baseline (%) were smaller from day 2 to 6 weeks than from baseline to 6 weeks. Long-term intraclass correlation coefficients were lowest between baseline and 6 weeks. No relevant impacts of feelings, motivation, or pain on reliability were detected. CONCLUSION: Reliability of isometric trunk strength measurements in patients with chronic low back pain is similar in older and younger patients. Short-term test repetition a few days after baseline is recommended, if clinically feasible, and especially in research evaluating the effects of exercise on strength.

Additive manufacturing of collagen scaffolds by three-dimensional plotting of highly viscous dispersions.

Additive manufacturing (AM) allows the free form fabrication of three-dimensional (3D) structures with distinct external geometry, fitting into a patient-specific defect, and defined internal pore architecture. However, fabrication of predesigned collagen scaffolds using AM-based technologies is challenging due to the low viscosity of collagen solutions, gels or dispersions commonly used for scaffold preparation. In the present study, we have developed a straightforward method which is based on 3D plotting of a highly viscous, high density collagen dispersion. The swollen state of the collagen fibrils at pH 4 enabled the homogenous extrusion of the material, the deposition of uniform strands and finally the construction of 3D scaffolds. Stabilization of the plotted structures was achieved by freeze-drying and chemical crosslinking with the carbodiimide EDC. The scaffolds exhibited high shape and dimensional fidelity and a hierarchical porosity consisting of macropores generated by strand deposition as well as an interconnected microporosity within the strands as result of the freeze-drying process. Cultivation of human mesenchymal stromal cells on the scaffolds, with and without adipogenic or osteogenic stimulation, revealed their cytocompatibility and potential applicability for adipose and bone tissue engineering.

Improved Sterilization of Sensitive Biomaterials with Supercritical Carbon Dioxide at Low Temperature.

The development of bio-resorbable implant materials is rapidly going on. Sterilization of those materials is inevitable to assure the hygienic requirements for critical medical devices according to the medical device directive (MDD, 93/42/EG). Biopolymer-containing biomaterials are often highly sensitive towards classical sterilization procedures like steam, ethylene oxide treatment or gamma irradiation. Supercritical CO2 (scCO2) treatment is a promising strategy for the terminal sterilization of sensitive biomaterials at low temperature. In combination with low amounts of additives scCO2 treatment effectively inactivates microorganisms including bacterial spores. We established a scCO2 sterilization procedure under addition of 0.25% water, 0.15% hydrogen peroxide and 0.5% acetic anhydride. The procedure was successfully tested for the inactivation of a wide panel of microorganisms including endospores of different bacterial species, vegetative cells of gram positive and negative bacteria including mycobacteria, fungi including yeast, and bacteriophages. For robust testing of the sterilization effect with regard to later application of implant materials sterilization all microorganisms were embedded in alginate/agarose cylinders that were used as Process Challenge Devices (PCD). These PCD served as surrogate models for bioresorbable 3D scaffolds. Furthermore, the impact of scCO2 sterilization on mechanical properties of polysaccharide-based hydrogels and collagen-based scaffolds was analyzed. The procedure was shown to be less compromising on mechanical and rheological properties compared to established low-temperature sterilization methods like gamma irradiation and ethylene oxide exposure as well as conventional steam sterilization. Cytocompatibility of alginate gels and scaffolds from mineralized collagen was compared after sterilization with ethylene oxide, gamma irradiation, steam sterilization and scCO2 treatment. Human mesenchymal stem cell viability and proliferation were not compromised by scCO2 treatment of these materials and scaffolds. We conclude that scCO2 sterilization under addition of water, hydrogen peroxide and acetic anhydride is a very effective, gentle, non-cytotoxic and thus a promising alternative sterilization method especially for biomaterials.

Age and gender related neuromuscular changes in trunk flexion-extension.

BACKGROUND: The root mean square surface electromyographic activity of lumbar extensor muscles during dynamic trunk flexion and extension from a standing position and task specific spine ranges of motion objectively assess muscle function in healthy young and middle age individuals. However, literature on neuromuscular activation and associated spine and hip kinematics in older individuals is sparse. This cross sectional study sought to examine the sex and age (<40 versus >60 years) related differences in the neuromuscular activation profiles of the lumbar extensors and the related spine and hip kinematics from healthy individuals during a standardized trunk flexion-extension task. METHODS: Twenty five older (13 females, 60-90 years) and 24 younger (12 females, 18-40 years) healthy individuals performed trunk flexion-extension testing by holding static positions at half-flexion way and full range of motion between standing and maximum trunk flexion. The associated lumbar extensor muscle activity was derived from measurements at standing, half, and maximum flexion positions. The range of motion at the hip and lumbar spine was recorded using 3d accelerometers attached to the skin overlying the multifidus and semispinalis thoracis muscles lateral to the L5 and T4 spinous processes, respectively. Statistical calculations were performed using a permutation ANOVA with bootstrap confidence intervals. RESULTS: The muscle activity in the half related to the maximum flexion position (half flexion relaxation ratio) was significantly smaller in older males when compared with younger males. Moreover, measurements revealed smaller activity changes from standing to the half and from half to the maximum flexion position in older compared to younger individuals. Older males displayed smaller gross trunk range of motion from standing to maximum flexion than any other group. CONCLUSIONS: Gender and normal aging significantly affect both the activation patterns of the lumbar extensor muscles and the kinematics of the trunk during a standardized trunk flexion-extension task. Measurement results from healthy young and middle age individuals should not be used for the assessment of individuals older than 60 years of age.

The potential use of spectral electromyographic fatigue as a screening and outcome monitoring tool of sarcopenic back muscle alterations.

BACKGROUND: To examine whether or not median frequency surface electromyographic (MF-EMG) back muscle fatigue monitoring would be able to identify alterations in back muscle function in elderly muscles, if a protocol was used that allowed optimum standardization of the processes underlying electromyographic fatigue, and whether these tests were reliable from day to day. METHODS: A total of 42 older (21 females; 67 (±10.5) years old) and 44 younger persons (19 females; 33 (±10) years) performed maximum isometric back extensions which were followed by one 30 s lasting 80% submaximum extension. Participants were seated on a dynamometer with their trunks 30° anteflexed, and they repeated all tests after 1-2 days and 6 weeks. SEMG was recorded bilaterally from the L1 (iliocostalis lumborum), L2 (longissimus), and L5 (multifidus) recording sites. Outcome variables included maximum back extension torque, initial MF-EMG (IMF-EMG), MF-EMG slope declines, and individual MF-EMG muscular imbalance scores. Two-factorial ANOVAs served to examine the age and gender-specific effects, and models from Generalizability Theory (G-Theory) were used for assessing retest-reliability. RESULTS: Maximum back extension moment was non-significantly smaller in elders. IMF-EMG was overall higher in elders, with significant differences at the L5 recordings sites. In the elderly, MF-EMG fatigue declines were significantly smaller in L5, in the recording with the most negative slope, or if the slope of all electrodes was considered. Retest reliability was unanimous in young and older persons. ICC-type measurements from G-Theory of both the IMF and the fatigue slopes ranged from 0.7 to 0.85. Absolute SEM values were found clinically acceptable for the IMF-EMG, but relatively high for the fatigue slope declines. CONCLUSIONS: The MF-EMG fatigue method is able to elucidate alterations of aging back muscles. This method, thus, might be suggested as a potential biomarker to objectively identify persons at risk for sarcopenia. Considering the clinical relevance of the IMF-EMG relative to the MF-EMG slope declines, spectral EMG may also be used as an outcome monitoring tool in elderly populations.

Reliability of isometric trunk moment measurements in healthy persons over 50 years of age.

OBJECTIVE: To determine the short- and long-term test-retest reliability of maximum isometric trunk moment measurements in healthy volunteers over 50 years of age, to compare these results with those from volunteers younger than 50 years, and to test whether volunteers' anticipatory emotional state affects the precision of these measurements. METHODS: Forty-two older persons (21 females; age range 50-90 years) and 44 younger persons (19 females; age range 18-49 years) performed maximum isometric trunk extensions, flexions, and rotations using dynamometers (DAVID, Fi, David Health Solutions Ltd, Helsinki, Finland). They repeated the tests after 1-2 days (short-term) and at 6 weeks (long-term). Retest-reliability was evaluated for age- and gender-specific subgroups, with assessment of intraclass correlation coefficient (ICC2,1) , standard error of measurement, smallest real difference, and smallest real difference, in percent. RESULTS: For the elderly group, smallest real difference, in percent values varied up to 33% and were similar to those obtained from young volunteers. Precision of the trunk rotation tests was lower than that of trunk flexion or extension. Retest agreement exceeded 0.75 (ICC2,1) for all tests, with no relevant differences observed between gender- and age-specific subgroups. Neither participants' motivation nor their anticipatory emotions correlated with the individual coefficients of variation of the trunk muscle moment measurements. CONCLUSION: Isometric maximum trunk extension and flexion moment measurements taken from healthy persons > 50 years old are as reliable as those from persons < 50 years old, and can be expected to enable an acceptable level of detection of expected changes in muscle strength parameters as a result of planned exercise interventions.

Diagnostic accuracy and reliability of muscle strength and endurance measurements in patients with chronic low back pain.

OBJECTIVE: Dynamometric trunk muscle strength and endurance tests are performed widely within the rehabilitation management of chronic low back pain. The aim of this study was to examine the accuracy and long-term reliability of these measurements in patients with chronic low back pain. DESIGN: Cross-sectional study. SUBJECTS: Thirty-two patients with chronic low back pain, 19 healthy controls and 15 patients with chronic headache matched for age, sex and body mass index. METHODS: Both patient groups and healthy controls performed isokinetic and isometric trunk extensor and flexor tests on a Biodex 2000 dynamometer. The Biering-Sørensen test served to examine back muscle endurance. Borg-Category-Ratio-Scales CR-10 rated participants' body experience immediately before and after the testing. Patients with chronic low back pain repeated measurements after 3 weeks. RESULTS: Among dynamometric tests, isokinetic measurements revealed the best area under the curve (AUC = 0.89) for the discrimination between patients with chronic low back pain and healthy controls. Reliability testing revealed highly significant learning effects for isometric trunk flexion and isokinetic measurements. The Biering-Sørensen test demonstrated excellent accuracy (AUC = 0.93) and no learning effects. Borg-category-ratio-scale ratings were not associated with the observed changes. CONCLUSION: In chronic low back pain dynamometric trunk muscle measures are limited to muscle function assessment purposes. Monitoring treatment outcome in these patients with these measures appears to be problematic because of learning effects. Based on our findings, we recommend the Biering-Sørensen test for management of chronic low back pain rehabilitation.

Low-back pain assessment based on the Brief ICF Core Sets: diagnostic relevance of motor performance and psychological tests.

OBJECTIVE: The Brief International Classification of Functioning, Disability and Health (ICF) Core Sets for chronic low-back pain (cLBP) have included the three body functional categories sensation of pain, muscle functions, and emotional functions. As the latter two categories represent umbrella terms, the objective of this research was to identify those clinical tests that most expediently substantiate these two categories. DESIGN: This case-control study included 32 consecutive cLBP patients and 19 nonathletic healthy controls (HC), matched in age, body mass index, and sex. All patients and HCs underwent a comprehensive standardized clinical examination, with objective muscle functions tests that measured trunk muscle strength, endurance, and postural performance. Assessment of the category emotional functions included the Symptom Checklist 90-Revised, the Beck depression inventory, the Fear-Avoidance Beliefs Questionnaire (FABQ-D), and body experience (Borg category ratio scales about exertion, tension, fear of harm, and (re-)/injury). RESULTS: Logistic regression analyses revealed back muscle endurance and somatization to explain 50% of the between-group variances. Furthermore, the variables of Sensory Organization Test (SOT) composite score and FABQ were best associated with disablement in cLBP. CONCLUSIONS: In the Brief ICF Core Set for cLBP, back muscle endurance tests best examined the category muscle functions, whereas somatization best examined that of emotional functions. Furthermore, both the SOT and the FABQ would, in addition to the aforementioned tests, optimize the functional diagnostic relevance of the two ICF categories for cLBP.