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Magnesium (Mg) has been intensively studied as a promising alternative material to inert metallic alloys for orthopedic fixation devices due to its biodegradable nature inside the body and its favorable biocompatibility. However, the low mechanical strength and rapid corrosion of Mg in physiological environments represent the main challenges for the development of Mg-based devices for orthopedic applications. A possible solution to these limitations is the incorporation of a small content of biocompatible nanoparticles into the Mg matrix to increase strength and possibly corrosion resistance of the resulting nanocomposites. In this work, the effect of adding boron nitride (BN) nanoparticles (0.5 and 1.5 vol.%) on the mechanical properties, corrosion behavior, and biocompatibility of Mg-based nanocomposites was investigated. The properties of the nanocomposites fabricated using powder metallurgy methods were assessed using microstructure analyses, microhardness, compression tests, in vitro corrosion, contact angle, and cytotoxicity tests. A significant increase in the microhardness, strength, and corrosion rates of Mg–BN nanocomposites was detected compared with those of pure Mg (0% BN). Crystalline surface post-corrosion byproducts were detected and identified via SEM, EDX, and XRD. Biocompatibility assessments showed that the incorporation of BN nanoparticles had no significant impact on the cytotoxicity of Mg and samples were hydrophilic based on the contact angle results. These results confirm that the addition of BN nanoparticles to the Mg matrix can increase strength and corrosion resistance without influencing cytotoxicity in vitro. Further investigation into the chemical behavior of nanocomposites in physiological environments is needed to determine the potential impact of corrosive byproducts. Surface treatments and formulation methods that would increase the viability of these materials in vivo are also needed.

First-Generation College Students (FGCSs) face myriad challenges including the lack of parental guidance, economic and social burdens, isolation, decreased belongingness, and lowered self-confidence making them at an increased risk of dropping out of college compared to their Continuing College Students (CCSs) colleagues. In addition, being in a multidisciplinary Science, Technology, Engineering, and Mathematics (STEM) field such as Biomedical Engineering (BMEG) is another challenge as it requires the integration of several disciplines. This study aims to maximize FGCSs' success and retention in Biomedical Engineering. We hypothesize that STEM-tailored faculty and peer mentoring that is focused on academic and professional development will significantly increase BMEG FGCSs' academic and professional success and enhance their belongingness to the engineering community. Study participants were assigned to either group; faculty mentoring combined with academic coaching or peer mentoring combined with academic coaching. Both quantitative and qualitative data were collected using two surveys; pre-mentoring and post-mentoring. Both faculty mentoring and peer mentoring led to increasing FGCSs' confidence, belongingness, and involvement in professional opportunities. To tackle the added challenge of studying a multidisciplinary STEM field to the challenges facing FGCSs, a mentorship program that is focused on enhancing self-confidence, sense of belonging and augmenting professional development can be employed to ensure the success, integration, and retention of FGCSs in multidisciplinary STEM fields such as Biomedical Engineering.

Recurrence of intervertebral disc (IVD) herniation is the most important factor leading to chronic low back pain and subsequent disability after discectomy. Efficacious annulus fibrosus (AF) repair strategy that delivers cells and biologics to IVD injury site is needed to limit the progression of disc degeneration and promote disc self-regeneration capacities after discectomy procedures. In this study, a biphasic mechanically-conditioned scaffold encapsulated with human adipose-derived stem cells (ASCs) is studied as a potential treatment strategy for AF defects. Equiaxial strains and frequencies were applied to ASCs-encapsulated scaffolds to identify the optimal loading modality to induce AF differentiation. Equiaxial loading resulted in 2–4 folds increase in secretion of extracellular matrix proteins and the reorganization of the matrix fibers and elongations of the cells along the load direction. Further, the equiaxial load induced region-specific differentiation of ASCs within the inner and outer regions of the biphasic scaffolds. Gene expression of AF markers was upregulated with 5–30 folds within the equiaxially loaded biphasic scaffolds compared to unstrained samples. The results suggest that there is a specific value of equiaxial strain favorable to differentiate ASCs towards AF lineage and that ASCs-embedded biphasic scaffold can potentially be utilized to repair the AF defects.

Mechanical loading bioreactors capable of applying uniaxial tensile strains are emerging to be a valuable tool to investigate physiologically relevant cellular signaling pathways and biochemical expression. In this study, we have introduced a simple and cost-effective uniaxial tensile strain bioreactor for the application of precise and homogenous uniaxial strains to 3D cell-encapsulated collagen constructs at physiological loading strains (0-12%) and frequencies (0.01-1 Hz). The bioreactor employs silicone-based loading chambers specifically designed to stretch constructs without direct gripping to minimize stress concentration at the ends of the construct and preserve its integrity. The loading chambers are driven by a versatile stepper motor ball-screw actuation system to produce stretching of the constructs. Mechanical characterization of the bioreactor performed through Finite Element Analysis demonstrated that the constructs experienced predominantly uniaxial tensile strain in the longitudinal direction. The strains produced were found to be homogenous over a 15 × 4 × 2 mm region of the construct equivalent to around 60% of the effective region of characterization. The strain values were also shown to be consistent and reproducible during cyclic loading regimes. Biological characterization confirmed the ability of the bioreactor to promote cell viability, proliferation, and matrix organization of cell-encapsulated collagen constructs. This easy-to-use uniaxial tensile strain bioreactor can be employed for studying morphological, structural, and functional responses of cell-embedded matrix systems in response to physiological loading of musculoskeletal tissues. It also holds promise for tissue-engineered strategies that involve delivery of mechanically stimulated cells at the site of injury through a biological carrier to develop a clinically useful therapy for tissue healing. Biotechnol. Bioeng. 2017;114: 1878-1887. © 2017 Wiley Periodicals, Inc.

Successful tissue engineering and regenerative therapy necessitate having extensive knowledge about mechanical milieu in engineered tissues and the resident cells. In this study, we have merged two powerful analysis tools, namely finite element analysis and stochastic analysis, to understand the mechanical strain within the tissue scaffold and residing cells and to predict the cell viability upon applying mechanical strains. A continuum-based multi-length scale finite element model (FEM) was created to simulate the physiologically relevant equiaxial strain exposure on cell-embedded tissue scaffold and to calculate strain transferred to the tissue scaffold (macro-scale) and residing cells (micro-scale) upon various equiaxial strains. The data from FEM were used to predict cell viability under various equiaxial strain magnitudes using stochastic damage criterion analysis. The model validation was conducted through mechanically straining the cardiomyocyte-encapsulated collagen constructs using a custom-built mechanical loading platform (EQUicycler). FEM quantified the strain gradients over the radial and longitudinal direction of the scaffolds and the cells residing in different areas of interest. With the use of the experimental viability data, stochastic damage criterion, and the average cellular strains obtained from multi-length scale models, cellular viability was predicted and successfully validated. This methodology can provide a great tool to characterize the mechanical stimulation of bioreactors used in tissue engineering applications in providing quantification of mechanical strain and predicting cellular viability variations due to applied mechanical strain.

It is crucial to replicate the micromechanical milieu of native tissues to achieve efficacious tissue engineering and regenerative therapy. In this study, we introduced an innovative loading platform, EQUicycler, that utilizes a simple, yet effective, and well-controlled mechanism to apply physiologically relevant homogenous mechanical equiaxial strain on three-dimensional cell-embedded tissue scaffolds. The design of EQUicycler ensured elimination of gripping effects through the use of biologically compatible silicone posts for direct transfer of the mechanical load to the scaffolds. Finite Element Modeling (FEM) was created to understand and to quantify how much applied global strain was transferred from the loading mechanism to the tissue constructs. In vitro studies were conducted on various cell lines associated with tissues exposed to equiaxial mechanical loading in their native environment. In vitro results demonstrated that EQUicycler was effective in maintaining and promoting the viability of different musculoskeletal cell lines and upregulating early differentiation of osteoprogenitor cells. By utilizing EQUicycler, collagen fibers of the constructs were actively remodeled. Residing cells within the collagen construct elongated and aligned with strain direction upon mechanical loading. EQUicycler can provide an efficient and cost-effective tool to conduct mechanistic studies for tissue engineered constructs designed for tissue systems under mechanical loading in vivo.

Mechanical loading bioreactors capable of applying uniaxial tensile strains are emerging to be a valuable tool to investigate physiologically relevant cellular signaling pathways and biochemical expression. In this study, we have introduced a simple and cost-effective uniaxial tensile strain bioreactor for the application of precise and homogenous uniaxial strains to 3D cell-encapsulated collagen constructs at physiological loading strains (0-12%) and frequencies (0.01-1 Hz). The bioreactor employs silicone-based loading chambers specifically designed to stretch constructs without direct gripping to minimize stress concentration at the ends of the construct and preserve its integrity. The loading chambers are driven by a versatile stepper motor ball-screw actuation system to produce stretching of the constructs. Mechanical characterization of the bioreactor performed through Finite Element Analysis demonstrated that the constructs experienced predominantly uniaxial tensile strain in the longitudinal direction. The strains produced were found to be homogenous over a 15 × 4 × 2 mm region of the construct equivalent to around 60% of the effective region of characterization. The strain values were also shown to be consistent and reproducible during cyclic loading regimes. Biological characterization confirmed the ability of the bioreactor to promote cell viability, proliferation, and matrix organization of cell-encapsulated collagen constructs. This easy-to-use uniaxial tensile strain bioreactor can be employed for studying morphological, structural, and functional responses of cell-embedded matrix systems in response to physiological loading of musculoskeletal tissues. It also holds promise for tissue-engineered strategies that involve delivery of mechanically stimulated cells at the site of injury through a biological carrier to develop a clinically useful therapy for tissue healing. Biotechnol. Bioeng. 2017;114: 1878-1887. © 2017 Wiley Periodicals, Inc.

The objective of this study was to understand the temporal relationship between in situ generated calcium content (mineralization) and the mechanical properties of an injectable orthobiologic bone-filler material. Murine derived osteoblast progenitor cells were differentiated using osteogenic factors and encapsulated within an injectable polycaprolactone nanofiber-collagen composite scaffold (PN-COL +osteo ) to evaluate the effect of mineralization on the mechanical properties of the PN-COL scaffold. A comprehensive study was conducted using both an experimental and a predictive analytical mechanical analysis for mechanical property assessment as well as an extensive in vitro biological analysis for in situ mineralization. Cell proliferation was evaluated using a PicoGreen dsDNA quantification assay and in situ mineralization was analyzed using both an alkaline phosphatase (ALP) assay and an Alizarin Red stain-based assay. Mineralized matrix formation was further evaluated using energy dispersive x-ray spectroscopy (EDS) and visualized using SEM and histological analyses. Compressive mechanical properties of the PN-COL scaffolds were determined using a confined compression stress-relaxation protocol and the obtained data was fit to the standard linear solid viscoelastic material mathematical model to demonstrate a relationship between increased in situ mineralization and the mechanical properties of the PN-COL scaffold. Cell proliferation was constant over the 21 day period. ALP activity and calcium concentration significantly increased at day 14 and 21 as compared to PN-COL −osteo with undifferentiated osteoblast progenitor cells. Furthermore, at day 21 EDS, SEM and von Kossa histological staining confirmed mineralized matrix formation within the PN-COL scaffolds. After 21 days, compressive modulus, peak stress, and equilibrium stress demonstrate significant increases of 3.4-fold, 3.3-fold, and 4.0-fold respectively due to in situ mineralization. Viscoelastic parameters calculated through the standard linear solid mathematical model fit to the stress-relaxation data also indicate improved mechanical properties after in situ mineralization. This investigation clearly demonstrates that in situ mineralization can increase the mechanical properties of an injectable orthobiologic scaffold and can possibly guide the design of an effective osteoconductive injectable material.

Determination of shakedown (SD) boundaries of 90-degree plain smooth pipe bends has recently received substantial attention by several researchers. However, scarce or almost no solid information is found within the literature regarding the determination of the shakedown boundary of cracked pipe bends. The current research presents two additions to the literature, namely, determination of shakedown boundary for a circumferentially cracked 90-degree pipe bend via a simplified technique utilizing the finite element (FE) method and introduction of failure-assessment diagrams (FADs) in compliance with the API 579 failure-for-service assessment of pressure vessel and piping components. The analyzed cracked pipe bend is subjected to the combined effect of steady internal pressure spectrum and cyclic in-plane closing (IPC) and opening (IPO) bending moments. Line spring elements (LSEs) are embedded in quadratic shell elements to model part-through cracks. FAD is obtained through linking the J-integral fracture mechanics parameter with the shakedown limit moments of the analyzed cracked 90-degree pipe bend. The LSE outcomes illustrated satisfactory results in comparison to the results of two verification studies: stress intensity factor (SIF) and limit load. Additionally, full elastic-plastic (ELPL) cyclic loading finite element analyses are conducted and the outcomes revealed very good correlation with the results obtained via the simplified technique. The maximum load carrying capacity (limit moment) and the elastic domain are also computed thereby generating a Bree diagram for the cracked pipe bend. Finally, Crack growth analysis is presented to complement the FAD.

In this study, we investigated whether nitric oxide (NO) generated using a non-thermal plasma system can mediate osteoblastic differentiation of osteoprogenitor cells without creating toxicity. Our objective was to create an NO delivery mechanism using NO-dielectric barrier discharge (DBD) plasma that can generate and transport NO with controlled concentration to the area of interest to regulate osteoprogenitor cell activity. We built a non-thermal atmospheric pressure DBD plasma nozzle system based on our previously published design and similar designs in the literature. The electrical and spectral analyses demonstrated that N2 dissociated into NO under typical DBD voltage–current characteristics. We treated osteoprogenitor cells (MC3T3-E1) using NO-plasma treatment system. Our results demonstrated that we could control NO concentration within cell culture media and could introduce NO into the intracellular space using NO-plasma treatment with various treatment times. We confirmed that NO-plasma treatment maintained cell viability and did not create any toxicity even with prolonged treatment durations. Finally, we demonstrated that NO-plasma treatment induced early osteogenic differentiation in the absence of pro-osteogenic growth factors/proteins. These findings suggest that through the NO-plasma treatment system we are able to generate and transport tissue-specific amounts of NO to an area of interest to mediate osteoprogenitor cell activity without subsequent toxicity. This opens up the possibility to develop DBD plasma-assisted tissue-specific NO delivery strategies for therapeutic intervention in the prevention and treatment of bone diseases.