In vitro models of soft tissue damage by implant-associated frictional shear stresses

Silicone elastomer medical implants are ubiquitous in medicine, particularly for breast augmentation. However, when these devices are placed within the body, disruption of the natural biological interfaces occurs, which significantly changes the native energy-dissipation mechanisms of living systems. These new interfaces can introduce non-physiological contact pressures and tribological conditions that provoke inflammation and soft tissue damage. Despite their significance, the biotribological properties of implant-tissue and implant-extracellular matrix (ECM) interfaces remain poorly understood. Here, we developed an in vitro model of soft tissue damage using a custom-built in situ biotribometer mounted onto a confocal microscope. Sections of commercially-available silicone breast implants with distinct and clinically relevant surface roughness (Ra = 0.2 ± 0.03 μm, 2.7 ± 0.6 μm, and 32 ± 7.0 μm) were mounted to spherically-capped hydrogel probes and slid against collagen-coated hydrogel surfaces as well as healthy breast epithelial (MCF10A) cell monolayers to model implant-ECM and implant-tissue interfaces. In contrast to the “smooth” silicone implants (Ra &lt; 10 μm), we demonstrate that the “microtextured” silicone implant (10 &lt; Ra &lt; 50 μm) induced higher frictional shear stress (τ &gt; 100 Pa), which led to greater collagen removal and cell rupture/delamination. Our studies may provide insights into post-implantation tribological interactions between silicone breast implants and soft tissues.</p

In vitro models of soft tissue damage by implant-associated frictional shear stresses

Silicone elastomer medical implants are ubiquitous in medicine, particularly for breast augmentation. However, when these devices are placed within the body, disruption of the natural biological interfaces occurs, which significantly changes the native energy-dissipation mechanisms of living systems. These new interfaces can introduce non-physiological contact pressures and tribological conditions that provoke inflammation and soft tissue damage. Despite their significance, the biotribological properties of implant-tissue and implant-extracellular matrix (ECM) interfaces remain poorly understood. Here, we developed an in vitro model of soft tissue damage using a custom-built in situ biotribometer mounted onto a confocal microscope. Sections of commercially-available silicone breast implants with distinct and clinically relevant surface roughness (Ra=0.2±0.03μm, 2.7±0.6μm, and 32±7.0μm) were mounted to spherically-capped hydrogel probes and slid against collagen-coated hydrogel surfaces as well as healthy breast epithelial (MCF10A) cell monolayers to model implant-ECM and implant-tissue interfaces. In contrast to the “smooth” silicone implants (Ra100  Pa), which led to greater collagen removal and cell rupture/delamination. Our studies may provide insights into post-implantation tribological interactions between silicone breast implants and soft tissues

GOCE Downward Continuation to the Earth’s Surface and Improvements to Local Geoid Modeling by FFT and LSC

One of the main applications of the gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite data is their combination with local gravity anomalies for geoid and gravity field modeling purposes. The aim of the present paper was the determination of an improved geoid model for the wider Hellenic area, using original GOCE SGG data filtered to retain only useful signals inside the measurement bandwidth (MBW) of the satellite. The filtered SGGs, originally at the satellite altitude, were projected to a mean orbit (MO) and then downward continued to the Earth’s surface (ES) in order to be combined with local gravity anomalies. For the projection to an MO, grids of disturbing gravity gradients from a global geopotential model (GGM) were used, computed per 1 km from the maximum satellite altitude to that of the MO. The downward continuation process was then undertaken using an iterative Monte Carlo (MC) simulated annealing method with GGM gravity anomalies on the ES used as ground truth data. The final geoid model over the wider Hellenic area was estimated, employing the remove–compute–restore method and both Fast Fourier Transform (FFT) and Least Squares Collocation (LSC). Gravity-only, GOCE-only and combined models using local gravity and GOCE data were determined and evaluation of the results was carried out against available GNSS/levelling data in the study area. From the results achieved, it was concluded that even when FFT is used, so that a combined grid of local gravity and GOCE data is used, improvements to the differences regarding GNSS/levelling data by 14.53% to 27.78% can be achieved. The geoid determination with LSC was focused on three different areas over Greece, with different characteristics in the topography and gravity variability. From these results, improvements from 14.73%, for the well-surveyed local data of Thessaly, to 32.88%, over the mountainous area of Pindos, and 57.10% for the island of Crete for 57.10% were found

Survival-Associated Cellular Response Maintained in Pancreatic Ductal Adenocarcinoma (PDAC) Switched Between Soft and Stiff 3D Microgel Culture

Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of all pancreatic cancer cases. Five-year survival rates have remained below 12% since the 1970s, in part due to the difficulty in detection prior to metastasis (migration and invasion into neighboring organs and glands). Mechanical memory is a concept that has emerged over the past decade that may provide a path toward understanding how invading PDAC cells "remember" the mechanical properties of their diseased ("stiff", elastic modulus, E ≈ 10 kPa) microenvironment even while invading a healthy ("soft", E ≈ 1 kPa) microenvironment. Here, we investigated the role of mechanical priming by culturing a dilute suspension of PDAC (FG) cells within a 3D, rheologically tunable microgel platform from hydrogels with tunable mechanical properties. We conducted a suite of acute (short-term) priming studies where we cultured PDAC cells in either a soft (E ≈ 1 kPa) or stiff (E ≈ 10 kPa) environment for 6 h, then removed and placed them into a new soft or stiff 3D environment for another 18 h. Following these steps, we conducted RNA-seq analyses to quantify gene expression. Initial priming in the 3D culture showed persistent gene expression for the duration of the study, regardless of the subsequent environments (stiff or soft). Stiff 3D culture was associated with the downregulation of tumor suppressors (LATS1, BCAR3, CDKN2C), as well as the upregulation of cancer-associated genes (RAC3). Immunofluorescence staining (BCAR3, RAC3) further supported the persistence of this cellular response, with BCAR3 upregulated in soft culture and RAC3 upregulated in stiff-primed culture. Stiff-primed genes were stratified against patient data found in The Cancer Genome Atlas (TCGA). Upregulated genes in stiff-primed 3D culture were associated with decreased survival in patient data, suggesting a link between patient survival and mechanical priming

An Optogenetic Platform to Dynamically Control the Stiffness of Collagen Hydrogels

The extracellular matrix (ECM) comprises a meshwork of biomacromolecules whose composition, architecture, and macroscopic properties, such as mechanics, instruct cell fate decisions during development and disease progression. Current methods implemented in mechanotransduction studies either fail to capture real-time mechanical dynamics or utilize synthetic polymers that lack the fibrillar nature of their natural counterparts. Here we present an optogenetic-inspired tool to construct light-responsive ECM mimetic hydrogels comprised exclusively of natural ECM proteins. Optogenetic tools offer seconds temporal resolution and submicron spatial resolution, permitting researchers to probe cell signaling dynamics with unprecedented precision. Here we demonstrated our approach of using SNAP-tag and its thiol-targeted substrate, benzylguanine-maleimide, to covalently attach blue-light-responsive proteins to collagen hydrogels. The resulting material (OptoGel), in addition to encompassing the native biological activity of collagen, stiffens upon exposure to blue light and softens in the dark. Optogels have immediate use in dissecting the cellular response to acute mechanical inputs and may also have applications in next-generation biointerfacing prosthetics

Leonardo da Vinci’s Friction Experiments: An Old Story Acknowledged and Repeated

Leonardo da Vinci (1452–1519) is universally regarded as a brilliant polymath, designer, astronomer, artist, philosopher, and a visionary engineer of the Renaissance era. Interestingly, due to the delayed discovery of several caches of his notebook pages (as late as the 1960s), his immense contribution to the field of tribology has only recently surfaced. From these salvaged documents, da Vinci’s three notable observations that preceded the development of the laws of friction were uncovered: (1) Friction is independent of apparent contact area, (2) the resistance of friction is directly proportional to applied load, and (3) friction has a consistent value of µ = 0.25. In this work, we have attempted to construct a nearly faithful recreation of Leonardo da Vinci’s apparatus for measuring friction based on his notebook illustrations and investigate the conditions under which Leonardo da Vinci’s experiments produced his findings. Our experiments, performed roughly 500 years later, reproduced Leonardo da Vinci’s findings of friction coefficients with wood of µ = 0.25, but only under conditions of roughly cut and brusquely squared samples of dry wood that were handled and sullied by hand in a fashion typical of wood working but inconsistent with the modern laboratory practice. Thus, our interpretation of Leonardo da Vinci’s findings is that these first tribological studies were actually performed on roughly cut and unpolished samples that had been handled extensively prior to and during testing; Such a procedure of sample preparation is entirely reasonable for the time period and suggests an active, dusty, and dynamic laboratory environment

Superlubricity of pH-responsive hydrogels in extreme environments

Poly(acrylamide-co-acrylic acid) (P(AAm-co-AA)) hydrogels are highly tunable and pH-responsive materials frequently used in biomedical applications. The swelling behavior and mechanical properties of these gels have been extensively characterized and are thought to be controlled by the protonation state of the acrylic acid (AA) through the regulation of solution pH. However, their tribological properties have been underexplored. Here, we hypothesized that electrostatics and the protonation state of AA would drive the tribological properties of these polyelectrolyte gels. P(AAm-co-AA) hydrogels were prepared with constant acrylamide (AAm) concentration (33&nbsp;wt%) and varying AA concentration to control the amount of ionizable groups in the gel. The monomer:crosslinker molar ratio (200:1) was kept constant. Hydrogel swelling, stiffness, and friction behavior were studied by systematically varying the acrylic acid (AA) concentration from 0-12&nbsp;wt% and controlling solution pH (0.35, 7, 13.8) and ionic strength (I = 0 or 0.25&nbsp;M). The stiffness and friction coefficient of bulk hydrogels were evaluated using a microtribometer and borosilicate glass probes as countersurfaces. The swelling behavior and elastic modulus of these polyelectrolyte hydrogels were highly sensitive to solution pH and poorly predicted the friction coefficient (µ), which decreased with increasing AA concentration. P(AAm-co-AA) hydrogels with the greatest AA concentrations (12&nbsp;wt%) exhibited superlubricity (µ = 0.005 ± 0.001) when swollen in unbuffered, deionized water (pH = 7, I = 0&nbsp;M) and 0.5&nbsp;M NaOH (pH = 13.8, I = 0.25&nbsp;M) (µ = 0.005 ± 0.002). Friction coefficients generally decreased with increasing AA and increasing solution pH. We postulate that tunable lubricity in P(AAm-co-AA) gels arises from changes in the protonation state of acrylic acid and electrostatic interactions between the probe and hydrogel surface

FIR, IIR and Wavelet Algorithms for the Rigorous Filtering of GOCE SGG Data to the GOCE MBW

Gravity field and steady-state Ocean Circulation Explorer (GOCE) data are strongly affected by noise and long-wavelength errors outside the satellite measurement bandwidth (MBW). One of the main goals in utilizing GOCE data for gravity field modeling is the application of filtering techniques that can remove gross errors and reduce low-frequency errors and high-frequency noise while preserving the original signal. This paper aims to present and analyze three filtering strategies used to de-noise the GOCE Level 2 data from long-wavelength correlated errors and noise. These strategies are Finite Impulse Response (FIR), Infinite Impulse Response (IIR), and Wavelet Multi-resolution Analysis (WL), which have been applied to GOCE residual second order derivatives of the gravity potential. Several experiments were performed for each filtering scheme in order to identify the ideal filtering parameters. The outcomes indicate that all the suggested filtering strategies proved to be effective in removing low-frequency errors while preserving the signals in the GOCE MBW, with FIR filtering providing the overall best results

Bioinspired Lubricity from Surface Gel Layers

Surface gel layers on commercially available contact lenses have been shown to reduce frictional shear stresses and mitigate damage during sliding contact with fragile epithelial cell layers in vitro. Spencer and co-workers recently demonstrated that surface gel layers could arise from oxygen-inhibited free-radical polymerization. In this study, polyacrylamide hydrogel shell probes (7.5 wt % acrylamide, 0.3 wt % N,N'-methylenebisacrylamide) were polymerized in three hemispherical molds listed in order of decreasing surface energy and increasing oxygen permeability: borosilicate glass, polyether ether ketone (PEEK), and polytetrafluoroethylene (PTFE). Hydrogel probes polymerized in PEEK and PTFE molds exhibited 100× lower elastic moduli at the surface (EPEEK* = 80 ± 31 and EPTFE* = 106 ± 26 Pa, respectively) than those polymerized in glass molds (Eglass* = 31,560 ± 1,570 Pa), in agreement with previous investigations by Spencer and co-workers. Biotribological experiments revealed that hydrogel probes with surface gel layers reduced frictional shear stresses against cells (τPEEK = 35 ± 15 and τPTFE = 22 ± 16 Pa) more than those without (τglass = 68 ± 15 Pa) and offered greater protection against cell damage when sliding against human telomerase-immortalized corneal epithelial (hTCEpi) cell monolayers. Our work demonstrates that the "mold effect" resulting in oxygen-inhibition polymerization creates hydrogels with surface gel layers that reduce shear stresses in sliding contact with cell monolayers, similar to the protection offered by gradient mucin gel networks across epithelial cell layers