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1.
Data Brief ; 55: 110687, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39049974

ABSTRACT

This data article presents a set of primary, analyzed, and digitalized mechanical testing datasets for nine copper alloys. The mechanical testing methods including the Brinell and Vickers hardness, tensile, stress relaxation, and low-cycle fatigue (LCF) testing were performed according to the DIN/ISO standards. The obtained primary testing data (84 files) mainly contain the raw measured data along with the testing metadata of the processes, materials, and testing machines. Five secondary datasets were also provided for each testing method by collecting the main meta- and measurement data from the primary data and the outputs of data analyses. These datasets give materials scientists beneficial data for comparative material selection analyses by clarifying the wide range of mechanical properties of copper alloys, including Brinell and Vickers hardness, yield and tensile strengths, elongation, reduction of area, relaxed and residual stresses, and LCF fatigue life. Furthermore, both the primary and secondary datasets were digitalized by the approach introduced in the research article entitled "Toward a digital materials mechanical testing lab" [1]. The resulting open-linked data are the machine-processable semantic descriptions of data and their generation processes and can be easily queried by semantic searches to enable advanced data-driven materials research.

2.
Foods ; 13(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39063250

ABSTRACT

Tomatoes are prone to mechanical damage due to improper gripping forces during automated harvest and postharvest processes. To reduce this damage, a dynamic viscoelastic model based on long short-term memory (LSTM) is proposed to fit the dynamic compression stress relaxation characteristics of the individual fruit. Furthermore, the classical stress relaxation models involved, the triple-element Maxwell and Caputo fractional derivative models, are compared with the LSTM model to validate its performance. Meanwhile, the LSTM and classical stress relaxation models are used to predict the stress relaxation characteristics of tomato fruit with different fruit sizes and compression positions. The results for the whole test dataset show that the LSTM model achieves a RMSE of 2.829×10-5 Mpa and a MAPE of 0.228%. It significantly outperforms the Caputo fractional derivative model by demonstrating a substantial enhancement with a 37% decrease in RMSE and a 36% reduction in MAPE. Further analysis of individual tomato fruit reveals the LSTM model's performance, with the minimum RMSE recorded at the septum position being 3.438×10-5 Mpa, 31% higher than the maximum RMSE at the locule position. Similarly, the lowest MAPE at the septum stands at 0.375%, outperforming the highest MAPE at the locule position by a significant margin of 90%. Moreover, the LSTM model consistently reports the smallest discrepancies between the predicted and observed values compared to classical stress relaxation models. This accuracy suggests that the LSTM model could effectively supplant classical stress relaxation models for predicting stress relaxation changes in individual tomato fruit.

3.
Gels ; 10(7)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39057449

ABSTRACT

Motivated by the enormous potential of hydrogels in regenerative medicine, new biocompatible gelatin-based hybrid hydrogels were developed through a green process using poly(ethylene glycol) diglycidyl ether as a cross-linking agent, adding carrageenan and chitosan polysaccharides to the network to better mimic the hybrid composition of native extracellular matrix. Overall, the hydrogels show suitable structural stability, high porosity and pore interconnectivity, good swellability, and finally, biocompatibility. Their mechanical behavior, investigated by tensile and compression tests, appears to be characterized by nonlinear elasticity with high compliance values, fast stress-relaxation, and good strain reversibility with no sign of mechanical failure for compressive loading-unloading cycles at relatively high deformation levels of 50%. Degradation tests confirm the hydrogel bioresorbability by gradual hydrolysis, during which the structural integrity of both materials is maintained, while their mechanical behavior becomes more and more compliant. Human Umbilical Cord-derived Mesenchymal Stem Cells (hUC-MSCs) were used to test the hydrogels as potential carriers for cell delivery in tissue engineering. hUC-MSCs cultured inside the hydrogels show a homogenous distribution and maintain their growth and viability for at least 21 days of culture, with an increasing proliferation trend. Hence, this study contributes to a further understanding of the potential use of hybrid hydrogels and hUC-MSCs for a wide range of biomedical applications, particularly in soft tissue engineering.

4.
J Colloid Interface Sci ; 676: 701-714, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39059277

ABSTRACT

Clear aligners undergo rapid stress relaxation in warm, moist oral environments, compromising therapeutic effectiveness and longevity of treatment. To develop an innovative multilayer composite material with improved stability and reduced stress release, we have engineered an innovative coating characterized by the surface aggregation of polydimethylsiloxane (PDMS), which imparts a pronounced hydrophobic effect. In addition, the chemically and physically cross-linked structure of the coating reduces the free volume created by molecular chain rearrangement owing to the presence of water molecules, thereby minimizing water penetration into the coating. Concurrently, the coating's internal structure is enriched with numerous polar functional groups to capture water molecules that penetrate into the inside of the coating. Through combination of these mechanisms, water molecules are effectively sequestered, thereby impeding their penetration into the polyethylene terephthalate glycol (PETG) substrate. The impact of the polydimethylsiloxane content on the triple-action water-resistance mechanisms was thoroughly examined using attenuated total reflection (ATR)-Fourier transform infrared (FTIR), water absorption rate, water swelling rate, and X-ray photoelectron spectroscopy. The low surface energy cross-linked polyurethane coating is applied to the polyethylene terephthalate glycol (PETG) substrate to create a novel composite material with specific mechanical properties and reduced stress relaxation. The composite material remains stable in simulated oral environment with linear swelling rate of 0.58 % upon water absorption. Additionally, the stress release rate of the composite material within 336 h is notably lower (23.64 %) than that of PETG (62.29 %).

5.
Proc Natl Acad Sci U S A ; 121(28): e2317711121, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38968101

ABSTRACT

Adult neural stem cells (NSCs) reside in the dentate gyrus of the hippocampus, and their capacity to generate neurons and glia plays a role in learning and memory. In addition, neurodegenerative diseases are known to be caused by a loss of neurons and glial cells, resulting in a need to better understand stem cell fate commitment processes. We previously showed that NSC fate commitment toward a neuronal or glial lineage is strongly influenced by extracellular matrix stiffness, a property of elastic materials. However, tissues in vivo are not purely elastic and have varying degrees of viscous character. Relatively little is known about how the viscoelastic properties of the substrate impact NSC fate commitment. Here, we introduce a polyacrylamide-based cell culture platform that incorporates mismatched DNA oligonucleotide-based cross-links as well as covalent cross-links. This platform allows for tunable viscous stress relaxation properties via variation in the number of mismatched base pairs. We find that NSCs exhibit increased astrocytic differentiation as the degree of stress relaxation is increased. Furthermore, culturing NSCs on increasingly stress-relaxing substrates impacts cytoskeletal dynamics by decreasing intracellular actin flow rates and stimulating cyclic activation of the mechanosensitive protein RhoA. Additionally, inhibition of motor-clutch model components such as myosin II and focal adhesion kinase partially or completely reverts cells to lineage distributions observed on elastic substrates. Collectively, our results introduce a unique system for controlling matrix stress relaxation properties and offer insight into how NSCs integrate viscoelastic cues to direct fate commitment.


Subject(s)
Cell Differentiation , Neural Stem Cells , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neural Stem Cells/physiology , Animals , Astrocytes/cytology , Astrocytes/metabolism , Astrocytes/physiology , Mice , Acrylic Resins/chemistry , rhoA GTP-Binding Protein/metabolism , Cells, Cultured , Neurons/metabolism , Neurons/physiology , Neurons/cytology , Extracellular Matrix/metabolism , Stress, Mechanical
6.
Adv Healthc Mater ; : e2401550, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075933

ABSTRACT

Alginate hydrogels are widely used as biomaterials for cell culture and tissue engineering due to their biocompatibility and tunable mechanical properties. Reducing alginate molecular weight is an effective strategy for modulating hydrogel viscoelasticity and stress relaxation behavior, which can significantly impact cell spreading and fate. However, current methods like gamma irradiation to produce low molecular weight alginates suffer from high cost and limited accessibility. Here, a facile and cost-effective approach to reduce alginate molecular weight in a highly controlled manner using serial autoclaving is presented. Increasing the number of autoclave cycles results in proportional reductions in intrinsic viscosity, hydrodynamic radius, and molecular weight of the polymer while maintaining its chemical composition. Hydrogels fabricated from mixtures of the autoclaved alginates exhibit tunable mechanical properties, with inclusion of lower molecular weight alginate leading to softer gels with faster stress relaxation behaviors. The method is demonstrated by establishing how viscoelastic relaxation affects the spreading of encapsulated fibroblasts and glioblastoma cells. Results establish repetitive autoclaving as an easily accessible technique to generate alginates with a range of molecular weights and to control the viscoelastic properties of alginate hydrogels, and demonstrate utility across applications in mechanobiology, tissue engineering, and regenerative medicine.

7.
ACS Appl Mater Interfaces ; 16(31): 41551-41561, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39042785

ABSTRACT

Although considerable progress has been made in developing different types of vitrimers, ongoing challenges remain in tuning their mechanical and rheological properties, self-healing, and adhesion. Here, we demonstrate a one-pot method to produce a novel double-network epoxy vitrimer using an aliphatic amine cross-linker with a siloxane covalent bond and an aromatic amine cross-linker with a disulfide covalent bond. When a controlled two-stage curing process is employed, the markedly different reactivities of aliphatic amine and aromatic amine with epoxy allow for sequential cross-linked network formation, leading to the development of a double network that incorporates two types of dynamic covalent bonds. As a result, the produced vitrimers exhibit controllable mechanical, thermal, and rheological properties, as well as recyclability. This is evidenced by a tensile strength as high as 72 MPa, while maintaining ∼10% elongation at break, a wide glass-transition temperature range from 91 to 171 °C, and an adjustable two-stage stress relaxation. These characteristics suggest opportunities to develop high-performance cross-linked polymers with specific responses to time and temperatures.

8.
Pharmacol Res ; 206: 107269, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38880313

ABSTRACT

Perivascular adipose tissue (PVAT) is known for being anti-contractile in healthy tissues. We discovered a new function of PVAT, the ability to stress relax and maintain a tone in response to a stretch. This is of note because stress relaxation has been attributed to smooth muscle, of which PVAT has none that is organized in a functional layer. We test the hypothesis the interactions of integrins with collagen play a role in stress relaxation. Our model is the thoracic aorta of the male Dahl SS rat. The PVAT and aorta were physically separated for most assays. Results from single nuclei RNA sequencing (snRNAseq) experiments, histochemistry and isometric contractility were also used. Masson Trichrome staining made evident the expression of collagen in PVAT. From snRNA seq experiments of the PVAT, mRNA for multiple collagen and integrin isoforms were detected: the α1 and ß1 integrin were most highly expressed. Pharmacological inhibition of integrin/collagen interaction was effected by the specific α1ß1 distintegrin obtustatin or general integrin inhibitor RGD peptide. RGD peptide but not obtustatin increased the stress relaxation. Cell-cell communication inference identified integrins αv and α5, two major RGD motif containing isoforms, as potential signaling partners of collagens. Collectively, these findings validate that stress relaxation can occur in a non-smooth muscle tissue, doing so in part through integrin-collagen interactions that may not include α1ß1 heterodimers. The importance of this lies in considering PVAT as a vascular layer that possesses mechanical functions.


Subject(s)
Adipose Tissue , Aorta, Thoracic , Collagen , Integrins , Rats, Inbred Dahl , Animals , Male , Adipose Tissue/metabolism , Integrins/metabolism , Aorta, Thoracic/metabolism , Collagen/metabolism , Rats
9.
Front Bioeng Biotechnol ; 12: 1374352, 2024.
Article in English | MEDLINE | ID: mdl-38694621

ABSTRACT

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon. Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology. Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%-80%, the high tensile modulus decreased by 38%-47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly. Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials.

10.
J Mech Behav Biomed Mater ; 155: 106571, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744118

ABSTRACT

Cardiac fibrosis refers to the abnormal accumulation of extracellular matrix within the cardiac muscle, leading to increased stiffness and impaired heart function. From a rheological standpoint, knowledge about myocardial behavior is still lacking, partially due to a lack of appropriate techniques to investigate the rheology of in vitro cardiac tissue models. 3D multicellular cardiac spheroids are powerful and versatile platforms for modeling healthy and fibrotic cardiac tissue in vitro and studying how their mechanical properties are modulated. In this study, cardiac spheroids were created by co-culturing neonatal rat ventricular cardiomyocytes and fibroblasts in definite ratios using the hanging-drop method. The rheological characterization of such models was performed by Atomic Force Microscopy-based stress-relaxation measurements on the whole spheroid. After strain application, a viscoelastic bi-exponential relaxation was observed, characterized by a fast relaxation time (τ1) followed by a slower one (τ2). In particular, spheroids with higher fibroblasts density showed reduction for both relaxation times comparing to control, with a more pronounced decrement of τ1 with respect to τ2. Such response was found compatible with the increased production of extracellular matrix within these spheroids, which recapitulates the main feature of the fibrosis pathophysiology. These results demonstrate how the rheological characteristics of cardiac tissue vary as a function of cellular composition and extracellular matrix, confirming the suitability of such system as an in vitro preclinical model of cardiac fibrosis.


Subject(s)
Fibrosis , Myocytes, Cardiac , Rheology , Spheroids, Cellular , Animals , Spheroids, Cellular/cytology , Spheroids, Cellular/pathology , Rats , Myocytes, Cardiac/cytology , Fibroblasts/cytology , Myocardium/cytology , Myocardium/pathology , Myocardium/metabolism , Rats, Wistar , Models, Biological
11.
Adv Healthc Mater ; : e2400472, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809180

ABSTRACT

Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior depends upon hydrogel stress relaxation creates a high demand for hydrogels with tissue-like viscoelastic properties. Here, a unique platform of synthetic polyethylene glycol (PEG) hydrogels in which star-shaped PEG molecules are conjugated with alendronate and/or RGD peptides, attaining modifiable degradability as well as flexible cell adhesion, is created. Novel reversible ionic interactions between alendronate and calcium phosphate nanoparticles, leading to versatile viscoelastic properties with varying initial elastic modulus and stress relaxation time, are identified. This new crosslinking mechanism provides shear-thinning properties resulting in differential cellular responses between cancer cells and stem cells. The novel hydrogel system is an improved design to the other ionic crosslink platforms and opens new avenues for the development of pathologically relevant cancer models, as well as minimally invasive approaches for cell delivery for potential regenerative therapies.

12.
Materials (Basel) ; 17(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38612043

ABSTRACT

Considerable development has been observed in the area of applying fractional-order rheological models to describe the viscoelastic properties of miscellaneous materials in the last few decades together with the increasingly stronger adoption of fractional calculus. The fractional Maxwell model is the best-known non-integer-order rheological model. A weighted least-square approximation problem of the relaxation modulus by the fractional Maxwell model is considered when only the time measurements of the relaxation modulus corrupted by additive noises are accessible for identification. This study was dedicated to the determination of the model, optimal in the sense of the integral square weighted model quality index, which does not depend on the particular sampling points applied in the stress relaxation experiment. It is proved that even when the real description of the material relaxation modulus is entirely unknown, the optimal fractional Maxwell model parameters can be recovered from the relaxation modulus measurements recorded for sampling time points selected randomly according to respective randomization. The identified model is a strongly consistent estimate of the desired optimal model. The exponential convergence rate is demonstrated both by the stochastic convergence analysis and by the numerical studies. A simple scheme for the optimal model identification is given. Numerical studies are presented for the materials described by the short relaxation times of the unimodal Gauss-like relaxation spectrum and the long relaxation times of the Baumgaertel, Schausberger and Winter spectrum. These studies have shown that the appropriate randomization introduced in the selection of sampling points guarantees that the sequence of the optimal fractional Maxwell model parameters asymptotically converge to parameters independent of these sampling points. The robustness of the identified model to the measurement disturbances was demonstrated by analytical analysis and numerical studies.

13.
J Biomed Opt ; 29(Suppl 1): S11530, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38632983

ABSTRACT

Significance: In the photoacoustic (PA) technique, the laser irradiation in the time domain (i.e., laser pulse duration) governs the characteristics of PA imaging-it plays a crucial role in the optical-acoustic interaction, the generation of PA signals, and the PA imaging performance. Aim: We aim to provide a comprehensive analysis of the impact of laser pulse duration on various aspects of PA imaging, encompassing the signal-to-noise ratio, the spatial resolution of PA imaging, the acoustic frequency spectrum of the acoustic wave, the initiation of specific physical phenomena, and the photothermal-PA (PT-PA) interaction/conversion. Approach: By surveying and reviewing the state-of-the-art investigations, we discuss the effects of laser pulse duration on the generation of PA signals in the context of biomedical PA imaging with respect to the aforementioned aspects. Results: First, we discuss the impact of laser pulse duration on the PA signal amplitude and its correlation with the lateral resolution of PA imaging. Subsequently, the relationship between the axial resolution of PA imaging and the laser pulse duration is analyzed with consideration of the acoustic frequency spectrum. Furthermore, we examine the manipulation of the pulse duration to trigger physical phenomena and its relevant applications. In addition, we elaborate on the tuning of the pulse duration to manipulate the conversion process and ratio from the PT to PA effect. Conclusions: We contribute to the understanding of the physical mechanisms governing pulse-width-dependent PA techniques. By gaining insight into the mechanism behind the influence of the laser pulse, we can trigger the pulse-with-dependent physical phenomena for specific PA applications, enhance PA imaging performance in biomedical imaging scenarios, and modulate PT-PA conversion by tuning the pulse duration precisely.


Subject(s)
Light , Photoacoustic Techniques , Spectrum Analysis , Signal-To-Noise Ratio , Acoustics , Lasers , Photoacoustic Techniques/methods
14.
Interface Focus ; 14(2): 20230068, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38618239

ABSTRACT

Locust Locusta migratoria exhibits remarkable aerial performances, relying predominantly on its hind wings that generate most of lift and thrust for flight. The mechanical properties of the cross-veins determine the deformation of the hind wing, which greatly affect the aerodynamic performance of flapping flight. However, whether the mechanical behaviours of the locust cross-veins change with loading rate is still unknown. In this study, cross-veins in four physiological regions (anterior-medial, anterior-lateral, posterior-medial and posterior-lateral) of the hind wing from adult locusts were investigated using uniaxial tensile test, stress relaxation test and fluorescence microscopy. It was found that the cross-veins were a type of viscoelastic material (including rate-independent elastic modulus and obvious stress relaxation). The cross-veins in the two anterior regions of the hind wing had significantly higher elastic moduli and higher ultimate tensile stress than those of its two posterior regions. This difference might be attributed to different resilin distribution patterns in the cross-veins. These findings furnish new insights into the mechanical characteristics of the locust cross-veins, which might deepen our understanding of the aerodynamic mechanisms of locust flapping flight.

15.
Article in English | MEDLINE | ID: mdl-38339988

ABSTRACT

Understanding skin responses to external forces is crucial for post-cutaneous flap wound healing. However, the in vivo viscoelastic behavior of scalp skin remains poorly understood. Personalized virtual surgery simulations offer a way to study tissue responses in relevant 3D geometries. Yet, anticipating wound risk remains challenging due to limited data on skin viscoelasticity, which hinders our ability to determine the interplay between wound size and stress levels. To bridge this gap, we reexamine three clinical cases involving scalp reconstruction using patient-specific geometric models and employ uncertainty quantification through a Monte Carlo simulation approach to study the effect of skin viscoelasticity on the final stress levels from reconstructive surgery. Utilizing the generalized Maxwell model via the Prony series, we can parameterize and efficiently sample a realistic range of viscoelastic response and thus shed light on the influence of viscoelastic material uncertainty in surgical scenarios. Our analysis identifies regions at risk of wound complications based on reported threshold stress values from the literature and highlights the significance of focusing on long-term responses rather than short-term ones.

16.
J Mech Behav Biomed Mater ; 152: 106434, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38350383

ABSTRACT

The reliability of computational models in orthopedic biomechanics depends often on the accuracy of the bone material properties. It is widely recognized that the mechanical response of trabecular bone is time-dependent, yet it is often ignored for the sake of simplicity. Previous investigations into the viscoelastic properties of trabecular bone have not explored the relationship between nonlinear stress relaxation and bone mineral density. The inclusion of this behavior could enhance the accuracy of simulations of orthopedic interventions, such as of primary fixation of implants. Although methods to quantify the viscoelastic behavior are known, the time period during which the viscoelastic properties should be investigated to obtain reliable predictions is currently unclear. Therefore, this study aimed to: 1) Investigate the duration of stress relaxation in bovine trabecular bone; 2) construct a material model that describes the nonlinear viscoelastic behavior of uniaxial stress relaxation experiments on trabecular bone; and 3) implement bone density into this model. Uniaxial compressive stress relaxation experiments were performed with cylindrical bovine femoral trabecular bone samples (n = 16) with constant strain held for 24 h. Additionally, multiple stress relaxation experiments with four ascending strain levels with a holding time of 30 min, based on the results of the 24-h experiment, were executed on 18 bovine bone cores. The bone specimens used in this study had a mean diameter of 12.80 mm and a mean height of 28.70 mm. A Schapery and a Superposition model were used to capture the nonlinear stress relaxation behavior in terms of applied strain level and bone mineral density. While most stress relaxation happened in the first 10 min (up to 53 %) after initial compression, the stress relaxation continued even after 24 h. Up to 69 % of stress relaxation was observed at 24 h. Extrapolating the results of 30 min of experimental data to 24 h provided a good fit for accuracy with much improved experimental efficiency. The Schapery and Superposition model were both capable of fitting the repeated stress relaxation in a sample-by-sample approach. However, since bone mineral density did not influence the time-dependent behavior, only the Superposition model could be used for a group-based model fit. Although the sample-by-sample approach was more accurate for an individual specimen, the group based approach is considered a useful model for general application.


Subject(s)
Bone Density , Cancellous Bone , Cattle , Animals , Reproducibility of Results , Biomechanical Phenomena , Femur
17.
Acta Biomater ; 177: 203-215, 2024 03 15.
Article in English | MEDLINE | ID: mdl-38354874

ABSTRACT

The tumor microenvironment (TME) in pancreatic adenocarcinoma (PDAC) is a complex milieu of cellular and non-cellular components. Pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF) are two major cell types in PDAC TME, whereas the non-cellular components are enriched with extracellular matrices (ECM) that contribute to high stiffness and fast stress-relaxation. Previous studies have suggested that higher matrix rigidity promoted aggressive phenotypes of tumors, including PDAC. However, the effects of dynamic viscoelastic matrix properties on cancer cell fate remain largely unexplored. The focus of this work was to understand the effects of such dynamic matrix properties on PDAC cell behaviors, particularly in the context of PCC/CAF co-culture. To this end, we engineered gelatin-norbornene (GelNB) based hydrogels with a built-in mechanism for simultaneously increasing matrix elastic modulus and viscoelasticity. Two GelNB-based macromers, namely GelNB-hydroxyphenylacetic acid (GelNB-HPA) and GelNB-boronic acid (GelNB-BA), were modularly mixed and crosslinked with 4-arm poly(ethylene glycol)-thiol (PEG4SH) to form elastic hydrogels. Treating the hybrid hydrogels with tyrosinase not only increased the elastic moduli of the gels (due to HPA dimerization) but also concurrently produced 1,2-diols that formed reversible boronic acid-diol bonding with the BA groups on GelNB-BA. We employed patient-derived CAF and a PCC cell line COLO-357 to demonstrate the effect of increasing matrix stiffness and viscoelasticity on CAF and PCC cell fate. Our results indicated that in the stiffened environment, PCC underwent epithelial-mesenchymal transition. In the co-culture PCC and CAF spheroid, CAF enhanced PCC spreading and stimulated collagen 1 production. Through mRNA-sequencing, we further showed that stiffened matrices, regardless of the degree of stress-relaxation, heightened the malignant phenotype of PDAC cells. STATEMENT OF SIGNIFICANCE: The pancreatic cancer microenvironment is a complex milieu composed of various cell types and extracellular matrices. It has been suggested that stiffer matrices could promote aggressive behavior in pancreatic cancer, but the effect of dynamic stiffening and matrix stress-relaxation on cancer cell fate remains largely undefined. This study aimed to explore the impact of dynamic changes in matrix viscoelasticity on pancreatic ductal adenocarcinoma (PDAC) cell behavior by developing a hydrogel system capable of simultaneously increasing stiffness and stress-relaxation on demand. This is achieved by crosslinking two gelatin-based macromers through orthogonal thiol-norbornene photochemistry and post-gelation stiffening with mushroom tyrosinase. The results revealed that higher matrix stiffness, regardless of the degree of stress relaxation, exacerbated the malignant characteristics of PDAC cells.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Gelatin , Hydrogels/pharmacology , Hydrogels/chemistry , Adenocarcinoma/pathology , Monophenol Monooxygenase/metabolism , Carcinoma, Pancreatic Ductal/pathology , Norbornanes/chemistry , Sulfhydryl Compounds/chemistry , Boronic Acids , Tumor Microenvironment
18.
Nano Lett ; 24(2): 672-680, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38166484

ABSTRACT

Dendritic Li deposition, an unstable solid-electrolyte interphase (SEI), and a nearly infinite relative volume change during cycling are three major obstacles to the practical application of Li metal batteries. Herein, we introduce a compressible and elastic reduced graphene oxide sponge (rGO-S) to simultaneously eliminate Li dendrite growth, stabilize the SEI, and accommodate the volume change. The volume change is contained by compressing and expanding the rGO-S anode, which effectively releases the Li plating-induced stress during cycling. The smooth and dense Li metal is deposited on rGO-S without dendrites, which preserves the SEI, reduces consumption of the electrolyte, and prevents the formation of Li debris. The half-cells employing rGO-S show a steady and high Coulombic efficiency. The Li@rGO-S symmetric cells demonstrate excellent cycling stability over 1200 cycles with a low overpotential. When paired with LiFePO4 (LFP), the Li@rGO-S||LFP full cells exhibit a high specific capacity (150.3 mAh g-1 at 1C), superior rate performance, and good capacity retention.

19.
Angew Chem Int Ed Engl ; 63(6): e202314738, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38055926

ABSTRACT

Dynamic polymer materials are highly valued substrates for 3D cell culture due to their viscoelasticity, a time-dependent mechanical property that can be tuned to resemble the energy dissipation of native tissues. Herein, we report the coupling of a cyclic thiosulfinate, mono-S-oxo-4-methyl asparagusic acid, to a 4-arm PEG-OH to prepare a disulfide-based dynamic covalent hydrogel with the addition of 4-arm PEG-thiol. Ring opening of the cyclic thiosulfinate by nucleophilic substitution results in the rapid formation of a network showing a viscoelastic fluid-like behaviour and relaxation rates modulated by thiol content through thiol-disulfide exchange, whereas its viscoelastic behaviour upon application as a small molecule linear crosslinker is solid-like. Further introduction of 4-arm PEG-vinylsulfone in the network yields a hydrogel with weeks-long cell culture stability, permitting 3D culture of cell types that lack robust proliferation, such as human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs). These cells display native behaviours such as cell elongation and spontaneous beating as a function of the hydrogel's mechanical properties. We demonstrate that the mode of dynamic cyclic thiosulfinate crosslinker presentation within the network can result in different stress relaxation profiles, opening the door to model tissues with disparate mechanics in 3D cell culture.


Subject(s)
Cell Culture Techniques , Hydrogels , Humans , Hydrogels/chemistry , Cell Culture Techniques/methods , Cell Culture Techniques, Three Dimensional , Sulfhydryl Compounds/chemistry , Disulfides/chemistry
20.
Macromol Biosci ; 24(1): e2300109, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37401723

ABSTRACT

Developing biomaterials for corneal repair and regeneration is crucial for maintaining clear vision. The cornea, a specialized tissue, relies on corneal keratocytes, that respond to their mechanical environment. Altering stiffness affects keratocyte behavior, but static stiffness alone cannot capture the dynamic properties of in vivo tissue. This study proposes that the cornea exhibits time-dependent mechanical properties, similar to other tissues, and aims to replicate these properties in potential therapeutic matrices. First, the cornea's stress relaxation properties are investigated using nanoindentation, revealing 15% relaxation within 10 seconds. Hydrogel dynamicity is then modulated using a specially formulated alginate-PEG and alginate-norbornene mixture. The tuning of the hydrogel's dynamicity is achieved through a photoinitiated norbornene-norbornene dimerization reaction, resulting in relaxation times ranging from 30 seconds to 10 minutes. Human primary corneal keratocytes are cultured on these hydrogels, demonstrating reduced αSMA (alpha smooth muscle actin) expression and increased filopodia formation on slower relaxing hydrogels, resembling their native phenotype. This in vitro model can enable the optimization of stress relaxation for various cell types, including corneal keratocytes, to control tissue formation. Combining stress relaxation optimization with stiffness assessment provides a more accurate tool for studying cell behavior and reduces mechanical mismatch with native tissues in implanted constructs.


Subject(s)
Alginates , Hydrogels , Humans , Hydrogels/pharmacology , Alginates/pharmacology , Sulfhydryl Compounds , Cornea , Norbornanes , Tissue Engineering/methods
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