Tunable Mechanical Properties Research Articles

(Invited) Scalable Manufacturing and Application of Piezoelectric Biomaterials

Piezoelectric materials are a group of important functional building blocks that interfacing the human body by coupling biomechanical energy and electricity. So far, many technology innovations have advanced piezoelectric materials and composites toward a broad range of biomedical applications, which possess unique biocompatibility and flexibility. Fundamentally, materials design and engineering draw the boundary where this technology may advance. In this talk, I introduce our most recent development of piezoelectric materials and composites that are particularly designed for implantable nanogenerator applications. First, I present our wafer-scale approach to creating piezoelectric biomaterial thin films based on amino acids. The self-assembled sandwich film and truss-like structures enabled both strong piezoelectricity and largely improved flexibility. Then, new ferroelectric composites are presented as a new material used in 3D printing for directly manufacturing of piezoelectric architectures with tunable piezoelectric and mechanical properties. Toward the end, novel applications of implantable piezoelectric materials are introduced, which enable the closed-loop electrostimulations for many biomedical therapeutics.

Engineered nascent living human tissues with unit programmability.

Leveraging human cells as materials precursors is a promising approach for fabricating living materials with tissue-like functionalities and cellular programmability. Here we describe a set of cellular units with metabolically engineered glycoproteins that allow cells to tether together to function as macrotissue building blocks and bioeffectors. The generated human living materials, termed as Cellgels, can be rapidly assembled in a wide variety of programmable three-dimensional configurations with physiologically relevant cell densities (up to 108 cells per cm3), tunable mechanical properties and handleability. Cellgels inherit the ability of living cells to sense and respond to their environment, showing autonomous tissue-integrative behaviour, mechanical maturation, biological self-healing, biospecific adhesion and capacity to promote wound healing. These living features also enable the modular bottom-up assembly of multiscale constructs, which are reminiscent of human tissue interfaces with heterogeneous composition. This technology can potentially be extended to any human cell type, unlocking the possibility for fabricating living materials that harness the intrinsic biofunctionalities of biological systems.

Exploring anti-corrosion properties and rheological behaviour of tannic acid and epoxidized soybean oil-based fully bio-based epoxy thermoset resins

This research explores the physicochemical attributes of a fully bio-epoxy thermoset aimed at serving as an anti-corrosion coating for safeguarding carbon steel structures in marine environments. Throughout this investigation, various epoxy thermosets formulations, based on epoxidized soybean oil (ESO) and tannic acid (TA), were synthesized by adjusting the initial ratios of epoxide:hydroxyl groups (epoxy:OH). These formulations were subsequently applied onto carbon steel substrates and subjected to thermal curing at moderate temperatures (170 °C) to evaluate their anti-corrosion effectiveness using electrochemical impedance spectroscopy (EIS). The examination of the total impedance values derived from EIS Bode diagrams (>106 Ω) revealed a notable anti-corrosion efficacy that endured over several months of immersion in 3.5 wt% NaCl solutions. In addition to electrochemical assessment, a rheological analysis was conducted to determine the optimal curing temperature for each formulation and to track the evolution of their mechanical properties throughout the curing process. Furthermore, the progression of corrosion at the coating-metal interphase was quantified using samples featuring artificially created notches to facilitate rapid water penetration, reaching the protected surface. Moreover, cross-cut and pull-off adhesion tests were conducted on coatings cured with various epoxide:hydroxyl ratios, yielding exceptional results on carbon steel substrates. Overall, a great potential for anti-corrosion protection has been demonstrated on the developed fully bio-based coatings with tuneable mechanical properties, regarding the initial component ratio, to reach the specific requirements for specific applications.

Injectable Dual Fenton/Enzymatically Cross-Linked Double-Network Hydrogels Based on Acrylic/Phenolic Polymers with Highly Reinforced and Tunable Mechanical Properties.

Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton's reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.

Knittable hydrogel fiber with physically amorphous structure for multi-mode sensing capacities

Integrating both green forming character and multifunctionality for physically crosslinked hydrogel fibers is challenging, but intensively desirable for emerging applications. Herein, the amorphous multi-scale structure for continuously spinning polyvinyl alcohol (PVA) hydrogel fibers is achieved with an innovatively suppressed-freezing strategy. In particular, the antifreezing salt with salting-in effect is introduced into precursor solution, in which an exceptionally homogeneous yet weak approach of polymer chains is available under weakened repelling behavior of ice crystals using liquid nitrogen as the coagulation bath. Hence, a totally amorphous network with release of free hydroxyl groups is constructed for freeze-thawed PVA hydrogel fibers, which is further stabilized by water evaporation induced densification of polymer network. Such particular multi-scale structure interestingly endows the physical hydrogel fibers with tunable mechanical properties of superior extendibility, flexibility and elasticity in a wide range, along with integrated properties of excellent transparency, antifreezing and long-term stability. Moreover, the hydrogel fibers could be knitted into fabric-like materials with arbitrary shapes, of which the extendibility and toughness are tremendously improved. Notably, benefiting from the high transparency and homogeneous structure, the physical fibers and the corresponding fabrics demonstrate light transmittance ability and deformation responsiveness, which retains even in extreme condition (−196 °C). Together with ionic-conductivity, the PVA hydrogel fibers/fabrics as strain sensors intriguingly represent conductive/optical multi-mode sensations, which are capable of dynamically monitoring subtle and sophisticated human movements. The combined advantages enable this new generation of physical hydrogel fibers to promise potential for applications in wearable electronics, biomedicine, and information transmission.

Homogeneously complexed alginate-chitosan hydrogel microspheres for the viability enhancement of entrapped hepatocytes

The future deployment of biomedicine fields will require a new generation of biodegradable, biocompatible, and non-toxic hydrogels. Alginate and chitosan, naturally occurring polymers, have gained significant interest for hydrogel applications. However, integrating chitosan within alginate-based hydrogels to form microspheres with homogeneous distribution and a tailored surface charge remains challenging. Herein, we report the design and fabrication of homogeneously complexed alginate-chitosan hydrogel microspheres, demonstrating their ability to enhance the viability and liver-specific functionalities of entrapped hepatocytes. By exploring and optimizing the pH and ratio of alginate and chitosan solutions, we achieved well-controlled physicochemical properties, including the degree of sphericity, hydrophilicity, charge property, and surface roughness. Unlike traditional alginate-based hydrogel microspheres, hepatocytes entrapped in homogeneous alginate-chitosan microspheres displayed enhanced viability and liver-specific functions, including albumin secretion, urea synthesis, and cytochrome P-450 enzymatic activity. This work illustrates a potential pathway for manufacturing functionalized microspheres with tunable mechanical properties and functionalities based on biocompatible alginate and chitosan for hepatocyte applications.

Nanocomposite Hydrogel Bioinks for 3D Bioprinting of Tumor Models.

In vitro tumor models were successfully constructed by 3D bioprinting; however, bioinks with proper viscosity, good biocompatibility, and tunable biophysical and biochemical properties are highly desirable for tumor models that closely recapitulated the main features of native tumors. Here, we developed a nanocomposite hydrogel bioink that was used to construct ovarian and colon cancer models by 3D bioprinting. The nanocomposite bioink was composed of aldehyde-modified cellulose nanocrystals (aCNCs), aldehyde-modified hyaluronic acid (aHA), and gelatin. The hydrogels possessed tunable gelation time, mechanical properties, and printability by controlling the ratio between aCNCs and gelatin. In addition, ovarian and colorectal cancer cells embedded in hydrogels showed high survival rates and rapid growth. By the combination of 3D bioprinting, ovarian and colorectal tumor models were constructed in vitro and used for drug screening. The results showed that gemcitabine had therapeutic effects on ovarian tumor cells. However, the ovarian tumor model showed drug resistance for oxaliplatin treatment.

Predicting the effect of binding molecules on the shape and mechanical properties of structured DNA assemblies

Chemo-mechanical deformation of structured DNA assemblies driven by DNA-binding ligands has offered promising avenues for biological and therapeutic applications. However, it remains elusive how to effectively model and predict their effects on the deformation and mechanical properties of DNA structures. Here, we present a computational framework for simulating chemo-mechanical change of structured DNA assemblies. We particularly quantify the effects of ethidium bromide (EtBr) intercalation on the geometry and mechanical properties of DNA base-pairs through molecular dynamics simulations and integrated them into finite-element-based structural analysis to predict the shape and properties of DNA objects. The proposed model captures various structural changes induced by EtBr-binding such as shape variation, flexibility modulation, and supercoiling instability. It enables a rational design of structured DNA assemblies with tunable shapes and mechanical properties by binding molecules.

Tunable Viscoelasticity of Alginate Hydrogels via Serial Autoclaving.

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.

Soy Protein-Based Wound Dressings: A Review of Their Preparation, Properties, and Perspectives.

Wound healing is a major challenge worldwide, and people have been researching wound dressings that can promote wound healing for decades. Natural biobased materials, such as polysaccharides and proteins, have been widely used in the development of wound dressings. Among them, soy protein-based materials have attracted the interest of a wide range of researchers due to their safety, biocompatibility, controlled degradation, and ability to be mixed with other materials. However, there has been a lack of comments on these soy protein-based wound dressings. This work reviews various forms of soy protein-based wound dressings, such as hydrogels, films, and others, which could be prepared through physical/chemical cross-linking with synthetic or natural polymers. The important role played by soy protein-based materials in the wound healing phase and their properties will be examined, such as their anti-inflammatory, antioxidant, angiogenesis-promoting, cellular biocompatibility, self-healing ability, adhesion, antimicrobial, and tunable mechanical properties. Additionally, insights into the market prospects and trends for soy protein dressings are provided, clarifying the enormous development potential of soy protein as a new type of wound repair material.

Molecularly Engineered Supramolecular Thermoresponsive Hydrogels with Tunable Mechanical and Dynamic Properties.

Synthetic supramolecular polymers and hydrogels in water are emerging as promising biomaterials due to their modularity and intrinsic dynamics. Here, we introduce temperature sensitivity into the nonfunctionalized benzene-1,3,5-tricarboxamide (BTA-EG4) supramolecular system by incorporating a poly(N-isopropylacrylamide)-functionalized (BTA-PNIPAM) moiety, enabling 3D cell encapsulation applications. The viscous and structural properties in the solution state as well as the mechanical and dynamic features in the gel state of BTA-PNIPAM/BTA-EG4 mixtures were investigated and modulated. In the dilute state (c ∼μM), BTA-PNIPAM acted as a chain capper below the cloud point temperature (Tcp = 24 °C) but served as a cross-linker above Tcp. At higher concentrations (c ∼mM), weak or stiff hydrogels were obtained, depending on the BTA-PNIPAM/BTA-EG4 ratio. The mixture with the highest BTA-PNIPAM ratio was ∼100 times stiffer and ∼10 times less dynamic than BTA-EG4 hydrogel. Facile cell encapsulation in 3D was realized by leveraging the temperature-sensitive sol-gel transition, opening opportunities for utilizing this hydrogel as an extracellular matrix mimic.

Chemically Recyclable Pseudo-Polysaccharides from Living Ring-Opening Polymerization of Glucurono-1,6-lactones.

Recent advances in synthetic methods and monomer design have given access to precision carbohydrate polymers that extend beyond native polysaccharides. In this article, we present the synthesis of a class of chemically recyclable ester-linked pseudo-polysaccharides via the living anionic ring-opening polymerization of glucurono-1,6-lactones. Notably, the pseudo-polysaccharides exhibited defined chain-end groups, well-controlled molecular weights, and narrow molecular weight distributions, all hallmarks of living polymerization. Furthermore, we demonstrate that our approach is modular, as evidenced by tunable glass transition temperatures (Tg) and the ability to produce both amorphous and semicrystalline polymers by adjusting the monomer side chain structure. Lastly, we showcased the complete catalytic chemical recycling of these pseudo-polysaccharides back to the monomers. The flexibility of the polymerization and the recyclability of these pseudo-polysaccharides promote a sustainable circular economy while offering the potential to access polysaccharide-like materials with tunable thermal and mechanical properties.

Triple-crosslinked double-network alginate/dextran/dendrimer hydrogel with tunable mechanical and adhesive properties: A potential candidate for sutureless keratoplasty

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.

Integrating Mechanics and Bioactivity: A Detailed Assessment of Elasticity and Viscoelasticity at Different Scales in 2D Biofunctionalized PEGDA Hydrogels for Targeted Bone Regeneration.

Methods for promoting and controlling the differentiation of human mesenchymal stem cells (hMSCs) in vitro before in vivo transplantation are crucial for the advancement of tissue engineering and regenerative medicine. In this study, we developed poly(ethylene glycol) diacrylate (PEGDA) hydrogels with tunable mechanical properties, including elasticity and viscoelasticity, coupled with bioactivity achieved through the immobilization of a mixture of RGD and a mimetic peptide of the BMP-2 protein. Despite the key relevance of hydrogel mechanical properties for cell culture, a standard for its characterization has not been proposed, and comparisons between studies are challenging due to the different techniques employed. Here, a comprehensive approach was employed to characterize the elasticity and viscoelasticity of these hydrogels, integrating compression testing, rheology, and atomic force microscopy (AFM) microindentation. Distinct mechanical behaviors were observed across different PEGDA compositions, and some consistent trends across multiple techniques were identified. Using a photoactivated cross-linker, we controlled the functionalization density independently of the mechanical properties. X-ray photoelectrin spectroscopy and fluorescence microscopy were employed to evaluate the functionalization density of the materials before the culturing of hMSCs on them. The cells cultured on all functionalized hydrogels expressed an early osteoblast marker (Runx2) after 2 weeks, even in the absence of a differentiation-inducing medium compared to our controls. Additionally, after only 1 week of culture with osteogenic differentiation medium, cells showed accelerated differentiation, with clear morphological differences observed among cells in the different conditions. Notably, cells on stiff but stress-relaxing hydrogels exhibited an overexpression of the osteocyte marker E11. This suggests that the combination of the functionalization procedure with the mechanical properties of the hydrogel provides a potent approach to promoting the osteogenic differentiation of hMSCs.

Self-healable, stimuli-responsive bio-ionic liquid and sodium alginate conjugated hydrogel with tunable Injectability and mechanical properties for the treatment of breast cancer

Designing stimuli-responsive drug delivery vehicles with higher drug loading capacity, sustained and targeted release of anti-cancer drugs and able to mitigate the shortcomings of traditional systems is need of hour. Herein, we designed stimuli-responsive, self-healable, and adhesive hydrogel through synergetic interaction between [Cho][Gly] (Choline-Glycine) and sodium alginate (SA). The hydrogel was formed as a result of non-covalent interaction between the components of the mixture forming the fibre kind morphology; confirmed through FTIR/computational analysis and SEM/AFM images. The hydrogel exhibited excellent mechanical strength, self-healing ability, adhesive character and most importantly; adjustable injectability. In vitro biocompatibility of the hydrogel was tested on HaCaT and MCF-7 cells, showing >92 % cell viability after 48 h. The hemolysis ratio (<4 %) of the hydrogel confirmed the blood compatibility of the hydrogel. When tested for drug-loading capacity, the hydrogel show 1500 times drug loading for the 5-fluorouracil (5-FU) against the SA based hydrogel. In vitro release data indicated that 5-FU have more preference towards the cancerous cell condition, i.e. acidic pH (>85 %), whereas the drug-loaded hydrogel successfully killed the MCF-7 and HeLa cell with a <IC50–1.92 mM value. The studied hydrogel paves way towards controlled and sustained delivery of anti-cancer drug for the treatment of breast cancer.

Advancing drug delivery and antimicrobial activity: Development and molecular docking analysis of quercetin-loaded pHEMA cryogel membranes

Quercetin (QT), found in Hypericum perforatum, Allium cepa, and citrus fruits, exhibits several pharmacological effects, including anti-cancer, anti-inflammatory, anti-bacterial, and anti-viral activities. Despite these significant benefits, the application of QT in pharmaceutical formulations is constrained by various challenges, such as its sensitivity to temperature, stability issues, low water solubility, and poor bioavailability. Cryogels, known for their remarkable physical properties such as swelling ratio, pore size, and pore interconnectivity, also offer tunable mechanical properties through the variation of monomer types, monomer-to-solvent ratios, and polymerization temperatures. In this study, we evaluated molecular docking analysis of QT against Staphylococcus aureus and developed QT-loaded pHEMA cryogel membranes (QT-pHEMA-GelCryoMem) to combat bacterial infections. The loading of QT within these membranes was characterized using Scanning Electron Microscopy and Fourier-transform infrared spectroscopy. The highest binding affinity of QT compound against different Staphylococcus aureus proteins (PDB ID:3U2D, PDB ID:2W9S, PDB ID:4H8E, PDB ID:3VSL, PDB ID:6U3Y and PDB ID:1JIJ) was found to be 8.429 kcal/mol for 2W9S while the lowest binding affinity was found to be -4.992 kcal/mol for 3VSL. The QT-pHEMA-GelCryoMem demonstrated good biocompatibility with HDFa cells and effective antimicrobial activity against Staphylococcus aureus. The obtained datas suggest that QT-pHEMA-GelCryoMem could be used in various applications, such as wound dressings, scaffolds, or food packaging.

Hydrogels Based on Proteins Cross-Linked with Carbonyl Derivatives of Polysaccharides, with Biomedical Applications.

Adding carbonyl groups into the hydrogel matrix improves the stability and biocompatibility of the hydrogels, making them suitable for different biomedical applications. In this review article, we will discuss the use of hydrogels based on polysaccharides modified by oxidation, with particular attention paid to the introduction of carbonyl groups. These hydrogels have been developed for several applications in tissue engineering, drug delivery, and wound healing. The review article discusses the mechanism by which oxidized polysaccharides can introduce carbonyl groups, leading to the development of hydrogels through cross-linking with proteins. These hydrogels have tunable mechanical properties and improved biocompatibility. Hydrogels have dynamic properties that make them promising biomaterials for various biomedical applications. This paper comprehensively analyzes hydrogels based on cross-linked proteins with carbonyl groups derived from oxidized polysaccharides, including microparticles, nanoparticles, and films. The applications of these hydrogels in tissue engineering, drug delivery, and wound healing are also discussed.

Multiscale Materials Engineering via Self-Assembly of Pentapeptide Derivatives from SARS CoV E Protein.

Short peptide-based supramolecular hydrogels hold enormous potential for a wide range of applications. However, the gelation of these systems is very challenging to control. Minor changes in the peptide sequence can significantly influence the self-assembly mechanism and thereby the gelation propensity. The involvement of SARS CoV E protein in the assembly and release of the virus suggests that it may have inherent self-assembling properties that can contribute to the development of hydrogels. Here, three pentapeptide sequences derived from C-terminal of SARS CoV E protein are explored with same amino acid residues but different sequence distributions and discovered a drastic difference in the gelation propensity. By combining spectroscopic and microscopic techniques, the relationship between peptide sequence arrangement and molecular assembly structure are demonstrated, and how these influence the mechanical properties of the hydrogel. The present study expands the variety of secondary structures for generating supramolecular hydrogels by introducing the 310-helix as the primary building block for gelation, facilitated by a water-mediated structural transition into β-sheet conformation. Moreover, these Fmoc-modified pentapeptide hydrogels/supramolecular assemblies with tunable morphology and mechanical properties are suitable for tissue engineering, injectable delivery, and 3D bio-printing applications.

Fabrication, characterization and numerical validation of a novel thin-wall hydrogel vessel model for cardiovascular research based on a patient-specific stenotic carotid artery bifurcation

In vitro vascular models, primarily made of silicone, have been utilized for decades for studying hemodynamics and supporting the development of implants for catheter-based treatments of diseases such as stenoses and aneurysms. Hydrogels have emerged as prominent materials in tissue-engineering applications, offering distinct advantages over silicone models for fabricating vascular models owing to their viscoelasticity, low friction, and tunable mechanical properties. Our study evaluated the feasibility of fabricating thin-wall, anatomical vessel models made of polyvinyl alcohol hydrogel (PVA-H) based on a patient-specific carotid artery bifurcation using a combination of 3D printing and molding technologies. The model’s geometry, elastic modulus, volumetric compliance, and diameter distensibility were characterized experimentally and numerically simulated. Moreover, a comparison with silicone models with the same anatomy was performed. A PVA-H vessel model was integrated into a mock circulatory loop for a preliminary ultrasound-based assessment of fluid dynamics. The vascular model's geometry was successfully replicated, and the elastic moduli amounted to 0.31 ± 0.007 MPa and 0.29 ± 0.007 MPa for PVA-H and silicone, respectively. Both materials exhibited nearly identical volumetric compliance (0.346 and 0.342% mmHg−1), which was higher compared to numerical simulation (0.248 and 0.290% mmHg−1). The diameter distensibility ranged from 0.09 to 0.20% mmHg−1 in the experiments and between 0.10 and 0.18% mmHg−1 in the numerical model at different positions along the vessel model, highlighting the influence of vessel geometry on local deformation. In conclusion, our study presents a method and provides insights into the manufacturing and mechanical characterization of hydrogel-based thin-wall vessel models, potentially allowing for a combination of fluid dynamics and tissue engineering studies in future cardio- and neurovascular research.

Tunable gelatin methacrylate polyethylene glycol diacrylate hydrogels for cell mechanosensing applications

Three-dimensional (3D) tissue-engineered scaffolds mimic the physiological environment of cells by providing essential structural support, biochemical cues, and the mechanical strength needed for cell adhesion, proliferation, migration, and differentiation. Hydrogels like polyethylene glycol diacrylate (PEGDA) are commonly used biomaterials for cell culture due to their affordability, tunable stiffness, and ability to efficiently transport nutrients and gases. However, PEGDA lacks cell adhesion sites essential for cell proliferation and migration and has limited degradability. Methacrylated gelatin (GelMA) produced from denatured bovine collagen, crosslinks under ultraviolet light (UV) resulting in a degradable hydrogel with cell adhesion sites. Here, we synthesized GelMA with variable degree of methacrylation and crosslinked it with PEGDA to produce cell scaffolds with independently tunable mechanical and biochemical properties by varying the ratios of the two polymers. We determined polymer ratios that resulted in scaffolds with different mechanical properties but the same gelatin concentrations (providing cell adhesion and degradation sites) as well as different gelatin concentrations but the same mechanical properties. With the developed scaffold library, we further used a design of experiments approach to probe the parameter space and perform detailed analysis on chemical composition-scaffold properties as well as scaffold properties-cell behavior correlations. Our findings showed that hydrogel properties such as modulus, swelling, pore size, and permeability, strongly depended on total polymer concentration and not on the GelMA fraction. GelMA significantly influenced cell spreading, while addition of any amount of PEGDA delayed cell spreading significantly. We suggest that such analysis will broaden the utility of the GelMA/PEGDA hydrogels, presenting a versatile platform for mechanosensing research in 3D environments.