Visualization of porosity and pore size gradients in electrospun scaffolds using laser metrology.

We applied a recently developed method, laser metrology, to characterize the influence of collector rotation on porosity gradients of electrospun polycaprolactone (PCL) widely investigated for use in tissue engineering. The prior- and post-sintering dimensions of PCL scaffolds were compared to derive quantitative, spatially-resolved porosity 'maps' from net shrinkage. Deposited on a rotating mandrel (200 RPM), the central region of deposition reaches the highest porosity, ~92%, surrounded by approximately symmetrical decreases to ~89% at the edges. At 1100 RPM, a uniform porosity of ~88-89% is observed. At 2000 RPM, the lowest porosity, ~87%, is found in the middle of the deposition, rebounding to ~89% at the edges. Using a statistical model of random fiber network, we demonstrated that these relatively small changes in porosity values produce disproportionately large variations in pore size. The model predicts an exponential dependence of pore size on porosity when the scaffold is highly porous (e.g., >80%) and, accordingly, the observed porosity variation is associated with dramatic changes in pore size and ability to accommodate cell infiltration. Within the thickest regions most likely to 'bottleneck' cell infiltration, pore size decreases from ~37 to 23 µm (38%) when rotational speeds increased from 200 to 2000 RPM. This trend is corroborated by electron microscopy. While faster rotational speeds ultimately overcome axial alignment induced by cylindrical electric fields associated with the collector geometry, it does so at the cost of eliminating larger pores favoring cell infiltration. This puts the bio-mechanical advantages associated with collector rotation-induced alignment at odds with biological goals. A more significant decrease in pore size from ~54 to ~19 µm (65%), well below the minimum associated with cellular infiltration, is observed from enhanced collector biases. Finally, similar predictions show that sacrificial fiber approaches are inefficient in achieving cell-permissive pore sizes.

Harnessing cortical plasticity via gabapentinoid administration promotes recovery after stroke.

Stroke causes devastating sensory-motor deficits and long-term disability due to disruption of descending motor pathways. Restoration of these functions enables independent living and therefore represents a high priority for those afflicted by stroke. Here, we report that daily administration of gabapentin, a clinically approved drug already used to treat various neurological disorders, promotes structural and functional plasticity of the corticospinal pathway after photothrombotic cortical stroke in adult mice. We found that gabapentin administration had no effects on vascular occlusion, haemodynamic changes nor survival of corticospinal neurons within the ipsilateral sensory-motor cortex in the acute stages of stroke. Instead, using a combination of tract tracing, electrical stimulation and functional connectivity mapping, we demonstrated that corticospinal axons originating from the contralateral side of the brain in mice administered gabapentin extend numerous collaterals, form new synaptic contacts and better integrate within spinal circuits that control forelimb muscles. Not only does gabapentin daily administration promote neuroplasticity, but it also dampens maladaptive plasticity by reducing the excitability of spinal motor circuitry. In turn, mice administered gabapentin starting 1 h or 1 day after stroke recovered skilled upper extremity function. Functional recovery persists even after stopping the treatment at 6 weeks following a stroke. Finally, chemogenetic silencing of cortical projections originating from the contralateral side of the brain transiently abrogated recovery in mice administered gabapentin, further supporting the conclusion that gabapentin-dependent reorganization of spared cortical pathways drives functional recovery after stroke. These observations highlight the strong potential for repurposing gabapentinoids as a promising treatment strategy for stroke repair.

Injectable, dispersible polysulfone-polysulfone core-shell particles for optical oxygen sensing.

Injectable sensors can significantly improve the volume of critical biomedical information emerging from the human body in response to injury or disease. Optical oxygen sensors with rapid response times can be achieved by incorporating oxygen-sensitive luminescent molecules within polymeric matrices with suitably high surface area to volume ratios. In this work, electrospraying utilizes these advances to produce conveniently injectable, oxygen sensing particles made up of a core-shell polysulfone-polysulfone structure containing a phosphorescent oxygen-sensitive palladium porphyrin species within the core. Particle morphology is highly dependent on solvent identity and electrospraying parameters; DMF offers the best potential for the creation of uniform, sub-micron particles. Total internal reflection fluorescence (TIRF) microscopy confirms the existence of both core-shell structure and oxygen sensitivity. The dissolved oxygen response time is rapid (<0.30 s), ideal for continuous real-time monitoring of oxygen concentration. The incorporation of Pluronic F-127 surfactant enables efficient dispersion; selection of an appropriate electrospraying solvent (DMF) yields particles readily injected even through a <100 µm diameter needle.

Injectable biodegradable bi-layered capsule for sustained delivery of bevacizumab in treating wet age-related macular degeneration.

Vascular endothelial growth factor (VEGF) is a key regulator of abnormal blood vessel growth. As such, bevacizumab-based inhibition of VEGF has been the clinically adopted strategy to treat colorectal and breast cancers as well as age-related macular degeneration (AMD). However, as the treatment of vascular diseases often requires a high drug concentration for a long period, the burst release of bevacizumab remains a critical limitation in anti-VEGF-based therapies. Maintaining bevacizumab at high concentrations over extended periods remains challenging due to insufficient drug loading capacity and drug-device interactions. We report the development of a polymeric based bi-layered capsule that could address these challenges by extending the release over one year, thereby providing an effective platform enabling treatment of chronic vascular diseases. Remarkably, the developed capsules have a bi-layered structure which ensures the structural integrity of the injectable capsules and appropriate diffusion of bevacizumab by providing optimal physical trapping and electrostatic interaction. Meanwhile, the central hollow design enables a higher drug loading to meet the need for long-term release of bevacizumab for several months to one year. Using an in vitro drug release assay, we demonstrated that the bi-layered capsule could produce longer-term local drug administration by intravitreal injection compared to previously reported devices. The capsules also present minimal toxicity and maintain anti-VEGF potency, suggesting that our approach may have the potential to treat vascular-related diseases using bevacizumab.

Effect of Electrospun Fiber Mat Thickness and Support Method on Cell Morphology.

Electrospun fiber mats (EFMs) are highly versatile biomaterials used in a myriad of biomedical applications. Whereas some facets of EFMs are well studied and can be highly tuned (e.g., pore size, fiber diameter, etc.), other features are under characterized. For example, although substrate mechanics have been explored by several groups, most studies rely on Young's modulus alone as a characterization variable. The influence of fiber mat thickness and the effect of supports are variables that are often not considered when evaluating cell-mechanical response. To assay the role of these features in EFM scaffold design and to improve understanding of scaffold mechanical properties, we designed EFM scaffolds with varying thickness (50-200 µm) and supporting methodologies. EFM scaffolds were comprised of polycaprolactone and were either electrospun directly onto a support, suspended across an annulus (3 or 10 mm inner diameter), or "tension-released" and then suspended across an annulus. Then, single cell spreading (i.e., Feret diameter) was measured in the presence of these different features. Cells were sensitive to EFM thickness and suspended gap diameter. Overall, cell spreading was greatest for 50 µm thick EFMs suspended over a 3 mm gap, which was the smallest thickness and gap investigated. These results are counterintuitive to conventional understanding in mechanobiology, which suggests that stiffer materials, such as thicker, supported EFMs, should elicit greater cell polarization. Additional experiments with 50 µm thick EFMs on polystyrene and polydimethylsiloxane (PDMS) supports demonstrated that cells can "feel" the support underlying the EFM if it is rigid, similar to previous results in hydrogels. These results also suggest that EFM curvature may play a role in cell response, separate from Young's modulus, possibly because of internal tension generated. These parameters are not often considered in EFM design and could improve scaffold performance and ultimately patient outcomes.

Sintered electrospun polycaprolactone for controlled model drug delivery.

Electrospinning has been used widely for drug delivery applications due to its versatility and ease of modification of spun fiber properties. Net drug loading and release is typically limited by the inherent surface-area of the sample. In a relatively novel approach, sintering of electrospun fiber was used to create a capsule favoring long-term delivery. We showed that electrospun polycaprolactone (PCL) retained its initial morphology out to 1042 days of in vitro exposure, illustrating its potential for extended performance. Sintering decreased the electrospun pore size by 10- and 28-fold following 56 and 57 °C exposures, respectively. At 58 and 59 °C, the PCL capsules lost all apparent surface porosity, but entrapped pores were observed in the 58 °C cross-section. The use of Rhodamine B (RhB, 479.02 g mol-1), Rose Bengal (RB, 1017.64 g mol-1) and albumin-fluorescein isothiocyanate conjugate from bovine serum (BSA-FITC, ~66,000 g mol-1) as model compounds demonstrated that release (RhB > RB ≫ BSA-FITC) is controlled both by molecular weight and available porosity. Interestingly, the ranking of release following sintering was 57 > 56 > 59 > 58 °C; COMSOL simulations explored the effects of capsule wall thickness and porosity on release rate. It was hypothesized that model drug adsorption on the available fiber surface-area (57 versus 56 °C) and entrapped porosity (59 versus 58 °C) could have also attributed to the observed ranking of release rates. While the 56 and 57 °C exposures allowed the bulk of the release to occur in <1 day, the capsules sintered at 58 and 59 °C exhibited release that continued after 12 days of exposure.

Understanding drug release from PCL/gelatin electrospun blends.

Electrospinning is one of the efficient processes to fabricate polymeric fibrous scaffolds for several biomedical applications. Several studies have published to demonstrate drug release from electrospun scaffolds. Blends of natural and synthetic electrospun fibers provide excellent platform to combine mechanical and bioactive properties. Drug release from polymer blends is a complex process. Drug release from polymer can be dominated by one or more of following mechanisms: polymer erosion, relaxation, and degradation. In this study, electrospun polycaprolactone (PCL)-gelatin blends are investigated to understand release mechanism of Rhodamine B dye. Also, this article summarizes the effect of high-pressure carbon dioxide on drug loading and release from PCL-gelatin fibers. Results indicate that release media diffusion is a dominant mechanism for PCL-gelatin electrospun fibers. Thickness of electrospun mat becomes critical for blends with gelatin. As gelatin is highly soluble in water and has tendency of gelation, it affects diffusion of release media in and out of scaffold. This article is a key step forward in understanding release from electrospun blends.

Ablation characteristics of electrospun core-shell nanofiber by femtosecond laser.

This study examined the femtosecond laser ablation properties of core and shell polymers their relationship to the ablation characteristics of core-shell nanofibers. The single-pulse ablation threshold of bulk polycaprolactone (PCL) was measured to be 2.12J/cm(2) and that of bulk polydimethylsiloxane (PDMS) was 4.07J/cm(2). The incubation coefficients were measured to be 0.82±0.02 for PCL and 0.53±0.03 for PDMS. PDMS-PCL core-shell and pure PCL nanofibers were fabricated by electrospinning. The energy/volume of pure PCL and PDMS-PCL core-shell nanofiber ablation was investigated by measuring linear ablation grooves made at different scanning speeds. At large scanning speed, higher energy/volume was required for machining PDMS-PCL nanofiber than for PCL nanofiber. However, at small scanning speed, comparable energy/volume was measured for PDMS-PCL and PCL nanofiber ablation. Additionally, in linear scanned ablation of PDMS-PCL fibers at small laser pulse energy and large scanning speed, there were partially ablated fibers where the shell was ablated but the core remained. This was attributed to the lower ablation threshold of the shell material.

Nanofiber-based paramagnetic probes for rapid, real-time biomedical oximetry.

EPR (electron paramagnetic resonance) based biological oximetry is a powerful tool that accurately and repeatedly measures tissue oxygen levels. In vivo determination of oxygen in tissues is crucial for the diagnosis and treatment of a number of diseases. Here, we report the first successful fabrication and remarkable properties of nanofiber sensors for EPR-oximetry applications. Lithium octa-n-butoxynaphthalocyanine (LiNc- BuO), an excellent paramagnetic oxygen sensor, was successfully encapsulated in 300-500 nm diameter fibers consisting of a core of polydimethylsiloxane (PDMS) and a shell of polycaprolactone (PCL) by electrospinning. This core-shell nanosensor (LiNc-BuO-PDMS-PCL) shows a linear dependence of linewidth versus oxygen partial pressure (pO2). The nanofiber sensors have response and recovery times of 0.35 s and 0.55 s, respectively, these response and recovery times are ~12 times and ~218 times faster than those previously reported for PDMS-LiNc-BuO chip sensors. This greater responsiveness is likely due to the high porosity and excellent oxygen permeability of the nanofibers. Electrospinning of the structurally flexible PDMS enabled the fabrication of fibers having tailored spin densities. Core-shell encapsulation ensures the non-exposure of embedded LiNc-BuO and mitigates potential biocompatibility concerns. In vitro evaluation of the fiber performed under exposure to cultured cells showed that it is both stable and biocompatible. The unique combination of biocompatibility due to the PCL 'shell,' the excellent oxygen transparency of the PDMS core, and the excellent oxygen-sensing properties of LiNc-BuO makes LiNc-BuO-PDMS-PCL platform promising for long-term oximetry and repetitive oxygen measurements in both biological systems and clinical applications.

Biomimetic microstructural reorganization during suture retention strength evaluation of electrospun vascular scaffolds.

Suture retention strength (SRS) is commonly used as a measure the ability of sutures to adhere implants to surrounding tissue. While SRS is widely employed, surprisingly its effects on graft microstructure have not been characterized. This is particularly germane to the broad utilization of electrospun implants in tissue engineering. These implants need to retain their initial nanoscale topography while simultaneously preserving clinically critical mechanical properties. We examined the suture-driven microstructural deformation of polycaprolactone electrospun to form both square and tubular SRS samples. The impact of fiber orientation (generally parallel or random orientation, orthogonally aligned) on the SRS of these vascular tissue equivalents was analyzed and compared to native and decellularized porcine vasculature. The initial state of the fiber clearly dictates the overall efficiency of scaffold utilization. SRS values for as-spun fibers at a thickness of 300 µm were found to be in the range of 1.59-4.78 N for the three orientations. Unexpectedly, random fibers provided the optimal SRS values based on both resistance to suture motion and the percentage of scaffold involvement. A "V-shaped" failure morphology is observed for both electrospun scaffolds and native tissue during SRS testing. Post-test fiber alignment in the tensile direction was visible in all initial fiber orientations similar to that of native tissue. These findings are significant as they allow us to employ new, counterintuitive biomimetic design criteria for nanofiber-based scaffolds in which reliable mechanical integration with the surrounding tissues via suture-based methods is important. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1525-1534, 2016.

Cancer cell aggregate hypoxia visualized in vitro via biocompatible fiber sensors.

To fully understand biological behavior in vitro often dictates that oxygen be reported at either a local or a cellular level. Oxygen sensors based on the luminescent quenching of a specific form of electrospun fiber were developed for measurement of both gaseous and dissolved oxygen concentrations. Electrospinning was used to fabricate "core-shell" fiber configurations in which oxygen-sensitive transition-metal porphyrin complexes are embedded in an optically clear, gas permeable polycarbonate polymer 'core' while polycaprolactone provided a protective yet biocompatible 'shell'. By taking advantage of the resulting high sensitivity and fast response of electrospun core-shell fiber sensors, we were able to locate and image hypoxic regions in contact with aggregates of glioblastoma cells. Nanoscale, biomimetic sensors containing oxygen-sensitive porphyrins are particularly well suited to biological applications. These 'smart' nanofiber based sensors do not consume oxygen, their mechanical and chemical characteristics can be finely tuned allowing tailoring of biocompatibility and microstructure. Core-shell nanofiber oxygen sensing fibers could provide real-time assessments of tumor cell response to pharmacological innovations designed to target hypoxic regions driving new knowledge and technological advancement.

Bearing-Foreign Material Deposition on Retrieved Co-Cr Femoral Heads: Composition and Morphology.

Bearing-foreign material deposition onto a femoral head can occur from contact with an acetabular shell due to dislocation, reduction, or subluxation. The purpose of this study was to comprehensively characterize deposit regions on retrieved cobalt-chrome femoral heads from metal-on-polyethylene total hip arthroplasties that had experienced such adverse events. The morphology, topography, and composition of deposition regions were characterized using macrophotography, optical profilometry, scanning electron microscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy. The deposit areas were relatively large, they were much rougher than the surrounding undamaged clean areas, and they displayed several distinct morphologies. Titanium alloy elements were the predominant constituents. Calcium and phosphorous were also detected within the deposit areas, in a composition that could nucleate abrasive hydroxyapatite. In addition, tungsten-rich particles, likely present as tungsten carbide, were observed on top of the titanium deposits. The increased roughness associated with these deposition features would be expected to accelerate damage and wear of the opposing liner and hence accelerate the development of osteolysis.

Glioma-astrocyte interactions on white matter tract-mimetic aligned electrospun nanofibers.

Gliomas are highly invasive forms of brain cancer comprising more than 50% of brain tumor cases in adults, and astrocytomas account for ∼60-70% of all gliomas. As a result of multiple factors, including enhanced migratory properties and extracellular matrix remodeling, even with current standards of care, mean survival time for patients is only ∼12 months. Because glioblastoma multiforme (GBM) cells arise from astrocytes, there is great interest in elucidating the interactions of these two cell types in vivo. Previous work performed on two-dimensional assays (i.e., tissue culture plastic and Boyden chamber assays) utilizes substrates that lack the complexities of the natural microenvironment. Here, we employed a three-dimensional, electrospun poly-(caprolactone) (PCL) nanofiber system (NFS) to mimic some features of topographical properties evidenced in vivo. Co-cultures of human GBM cells and rat astrocytes, as performed on the NFS, showed a significant increase in astrocyte GFAP expression, particularly in the presence of extracellular matrix (ECM) deposited by GBM cells. In addition, GBM migration increased in the presence of astrocytes or soluble factors (i.e., conditioned media). However, the presence of fixed astrocytes acted as an antagonist, lowering GBM migration rates. This data suggests that astrocytes and GBM cells interact through a multitude of pathways, including soluble factors and direct contact. This work demonstrates the potential of the NFS to duplicate some topographical features of the GBM tumor microenvironment, permitting analysis of topographical effects in GBM migration.

Microscale Sensing of Oxygen via Encapsulated Porphyrin Nanofibers: Effect of Indicator and Polymer "Core" Permeability.

Biomimetic polymer nanofibers integrate sensing capabilities creating utility across many biological and biomedical applications. We created fibers consisting of either a poly(ether sulfone) (PES) or a polysulfone (PSU) core coated by a biocompatible polycaprolactone (PCL) shell to facilitate cell attachment. Oxygen sensitive luminescent probes Pt(II) meso-tetra(pentafluorophenyl)porphine (PtTFPP) or Pd(II) meso-tetra(pentafluorophenyl)porphine (PdTFPP), were incorporated in the core via single-step coaxial electrospinning providing superior sensitivity, high brightness, linear response, and excellent stability. Both PES-PCL and PSU-PCL fibers provide more uniform probe distribution than polydimethylsiloxane (PDMS). PSU-based sensing fibers possessed optimum sensitivity due to their relatively higher oxygen permeability. During exposure to 100% nitrogen and 100% oxygen, PES-PCL fiber displayed an I0/I100 value of 6.7; PSU-PCL exhibited a value of 8.9 with PtTFPP as the indicator. In contrast, PdTFPP-containing fibers possess higher sensitivity due to the long porphyrin lifetime. The corresponding I0/I100 values were 80.6 and 106.7 for the PES-PCL and PSU-PCL matrices, respectively. The response and recovery times were 0.24/0.39 s for PES-PCL and 0.38/0.83 s for PSU-PCL which are 0.12 and 0.11 s faster, respectively, than the Pt-based porphyrin in the same matrices. Paradoxically, lower oxygen permeabilities make these polymers better suited to measuring higher (i. e., ∼20%) oxygen contents than PDMS. Individual fiber sensing was studied by fluorescence spectrometry and at a sub-micrometer scale by total internal reflection fluorescence (TIRF). Specific polymer blends relate polymer composition to the resulting sensor properties. All compositions displayed linear Stern-Volmer plots; sensitivity could be tailored by matrix or the sensing probe selection.

Actin grips: circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells.

Interaction of endothelial-lineage cells with three-dimensional substrates was much less studied than that with flat culture surfaces. We investigated the in vitro attachment of both mature endothelial cells (ECs) and of less differentiated EC colony-forming cells to poly-ε-capro-lactone (PCL) fibers with diameters in 5-20 µm range ('scaffold microfibers', SMFs). We found that notwithstanding the poor intrinsic adhesiveness to PCL, both cell types completely wrapped the SMFs after long-term cultivation, thus attaining a cylindrical morphology. In this system, both EC types grew vigorously for more than a week and became increasingly more differentiated, as shown by multiplexed gene expression. Three-dimensional reconstructions from multiphoton confocal microscopy images using custom software showed that the filamentous (F) actin bundles took a conspicuous ring-like organization around the SMFs. Unlike the classical F-actin-containing stress fibers, these rings were not associated with either focal adhesions or intermediate filaments. We also demonstrated that plasma membrane boundaries adjacent to these circular cytoskeletal structures were tightly yet dynamically apposed to the SMFs, for which reason we suggest to call them 'actin grips'. In conclusion, we describe a particular form of F-actin assembly with relevance for cytoskeletal organization in response to biomaterials, for endothelial-specific cell behavior in vitro and in vivo, and for tissue engineering.

Fabrication of functional nanofibers through post-nanoparticle functionalization.

A facile method is developed to functionalize nanofiber surfaces with nanoparticles (NPs) through dithiocarbamate chemistry. Gold nanoparticles (AuNPs) and quantum dots (QDs) are immobilized on the nanofiber surface. These surfaces provide scaffolds for further supramolecular functionalization, as demonstrated through the Förster resonance energy transfer (FRET) pairing of QD-decorated fibers and fluorescent proteins.

THA Retrievals: The Need to Mark the Anatomic Orientation of the Femoral Head.

The hypothesis of this study was that the rotational orientation of femoral head damage would greatly affect the volumetric wear rate of the opposing polyethylene (PE) liner. Damage on twenty retrieved cobalt-chromium femoral heads was simulated in a validated damage-feature-based finite element model. For each individual retrieval, the anatomic orientation of the femoral head about the femoral neck axis was systematically varied, in 30° increments. The PE wear rate differential between the maximum- versus minimum-wear orientations was often sizable, as high as 7-fold. Knowing the correct femoral head anatomic orientation is therefore important when analyzing the effects of femoral head damage on PE liner wear. Surgeons retrieving modular femoral heads should routinely mark the anatomic orientation of those components.

Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'.

BACKGROUND: Aggressive metastatic breast cancer cells seemingly evade surgical resection and current therapies, leading to colonization in distant organs and tissues and poor patient prognosis. Therefore, high-throughput in vitro tools allowing rapid, accurate, and novel anti-metastatic drug screening are grossly overdue. Conversely, aligned nanofiber constitutes a prominent component of the late-stage breast tumor margin extracellular matrix. This parallel suggests that the use of a synthetic ECM in the form of a nanoscale model could provide a convenient means of testing the migration potentials of cancer cells to achieve a long-term goal of providing clinicians an in vitro platform technology to test the efficacy of novel experimental anti-metastatic compounds. METHODS: Electrospinning produces highly aligned, cell-adhesive nanofiber matrices by applying a strong electric field to a polymer-containing solution. The resulting fibrous microstructure and morphology closely resembles in vivo tumor microenvironments suggesting their use in analysis of migratory potentials of metastatic cancer cells. Additionally, a novel interface with a gel-based delivery system creates CXCL12 chemotactic gradients to enhance CXCR4-expressing cell migration. RESULTS: Cellular dispersions of MCF-10A normal mammary epithelial cells or human breast cancer cells (MCF-7 and MDA-MB-231) seeded on randomly-oriented nanofiber exhibited no significant differences in total or net distance traveled as a result of the underlying topography. Cells traveled ~2-5 fold greater distances on aligned fiber. Highly-sensitive MDA-MB-231 cells displayed an 82% increase in net distance traversed in the presence of a CXCL12 gradient. In contrast, MCF-7 cells exhibited only 31% increase and MCF-10A cells showed no statistical difference versus control or vehicle conditions. MCF-10A cells displayed little sensitivity to CXCL12 gradients, while MCF-7 cells displayed early sensitivity when CXCL12 concentrations were higher. MDA-MB-231 cells displayed low relative expression levels of CXCR4, but high sensitivity resulting in 55-fold increase at late time points due to CXCL12 gradient dissipation. CONCLUSIONS: This model could create clinical impact as an in vitro diagnostic tool for rapid assessment of tumor needle biopsies to confirm metastatic tumors, their invasiveness, and allow high-throughput drug screening providing rapid development of personalized therapies.

Distinctive damage patterns on THA metal bearing surfaces: case studies.

Retrieval analysis of total joint arthroplasty components has primarily focused on assessing wear or other damage to polyethylene components. As damage to the opposing bearing surface can accelerate polyethylene wear and damage, and especially with the use of hard-on-hard articulations, retrieval analysis benefits from incorporating evaluation of hard bearing surfaces as well. The purpose of this study is to report six case studies of metal bearing surfaces with distinctive damage patterns, to interpret them in the context of adverse events plausibly responsible for their creation, and to suggest their likely clinical or scientific significance. The specific damage patterns reported here are 1) extensive scraping, 2) circumferential discoloration, 3) a long chain of periodic micro-indentations, 4) pitting with deposits, 5) scratches with small-radius directional changes, and 6) indentation with scraping.

Hemoglobin regulates the migration of glioma cells along poly(ε-caprolactone)-aligned nanofibers.

Aligned fibers have been shown to facilitate cell migration in the direction of fiber alignment while oxygen (O2 )-carrying solutions improve the metabolism of cells in hypoxic culture. Therefore, U251 aggregate migration on poly(ε-caprolactone) (PCL)-aligned fibers was studied in cell culture media supplemented with the O2 storage and transport protein hemoglobin (Hb) obtained from bovine, earthworm and human sources at concentrations ranging from 0 to 5 g/L within a cell culture incubator exposed to O2 tensions ranging from 1 to 19% O2 . Individual cell migration was quantified using a wound healing assay. In addition, U251 cell aggregates were developed and aggregate dispersion/cell migration quantified on PCL-aligned fibers. The results of this work show that the presence of bovine or earthworm Hb improved individual cell viability at 1% O2 , while human Hb adversely affected cell viability at increasing Hb concentrations and decreasing O2 levels. The control data suggests that decreasing the O2 tension in the incubator from 5 to 1% O2 decreased aggregate dispersion on the PCL-aligned fibers. However, the addition of bovine Hb at 5% O2 significantly improved aggregate dispersion. At 19% O2 , Hb did not impact aggregate dispersion. Also at 1% O2 , aggregate dispersion appeared to increase in the presence of earthworm Hb, but only at the latter time points. Taken together, these results show that Hb-based O2 carriers can be utilized to improve O2 availability and the migration of glioma spheroids on nanofibers.