Diacrylate Hydrogels Research Articles

A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics

Patients with aortic heart valve disease are limited to valve replacements that lack the ability to grow and remodel. This presents a major challenge for pediatric patients who require a valve capable of somatic growth and at a smaller size. A patient-specific heart valve capable of growth and remodeling while maintaining proper valve function would address this major issue. Here, we recreate the native valve leaflet structure composed of poly-ε-caprolactone (PCL) and cell-laden gelatin-methacrylate/poly (ethylene glycol) diacrylate (GelMA/PEGDA) hydrogels using 3D printing and molding, and then evaluate the ability of the multilayered scaffold to produce collagen matrix under physiological shear stress conditions. We also characterized the valve hemodynamics under aortic physiological flow conditions. The valve's fibrosa layer was replicated by 3D printing PCL in a circumferential direction similar to collagen alignment in the native leaflet, and GelMA/PEGDA sustained and promoted cell viability in the spongiosa/ventricularis layers. We found that collagen type I production can be increased in the multilayered scaffold when it is exposed to pulsatile shear stress conditions over static conditions. When the PCL component was mounted onto a valve ring and tested under physiological aortic valve conditions, the hemodynamics were comparable to commercially available valves. Our results demonstrate that a structurally representative valve leaflet can be generated using 3D printing and that the PCL layer of the leaflet can sustain proper valve function under physiological aortic valve conditions.

Effect of Loop Defects on the High Strain Rate Behavior of PEGDA Hydrogels: A Molecular Dynamics Study.

The high strain rate behavior of nonideal poly(ethylene glycol) diacrylate hydrogels under uniaxial tension and transient-state shear deformations is investigated using molecular dynamics (MD) simulations. This work specifically focuses on the influence of first-order loop defects, including their effect on topological evolutions. Two approaches are proposed to systematically introduce first-order loops, allowing separate and controllable investigations of effective cross-link functionality and cross-link density. MD simulations confirm that first-order loop defects are elastically inactive, but the topological disruptions caused by the presence of loop defects influence mechanical behavior. For decreasing effective cross-link functionality but constant cross-link density, a weaker tensile stress-strain response and decreasing shear-thickening behavior are observed. This is due to nonaffine translation of cross-link junction positions during deformation. Hydrogels with lower cross-link density but constant effective functionality show a stronger stress-strain response and an earlier transition between entropic and enthalpic deformation regimes. This behavior is correlated to changes in mesh size caused by the introduction of loops within an elastically active network. However, the resulting range of cross-link densities is not sufficient to cause measurable changes in shear-thickening behavior. To conclude, reductions in effective cross-link functionality are more important to high strain rate behavior than reductions in cross-link density.

Microfluidic deformability-activated sorting of single particles

Mechanical properties have emerged as a significant label-free marker for characterizing deformable particles such as cells. Here, we demonstrated the first single-particle-resolved, cytometry-like deformability-activated sorting in the continuous flow on a microfluidic chip. Compared with existing deformability-based sorting techniques, the microfluidic device presented in this work measures the deformability and immediately sorts the particles one-by-one in real time. It integrates the transit-time-based deformability measurement and active hydrodynamic sorting onto a single chip. We identified the critical factors that affect the sorting dynamics by modeling and experimental approaches. We found that the device throughput is determined by the summation of the sensing, buffering, and sorting time. A total time of ~100 ms is used for analyzing and sorting a single particle, leading to a throughput of 600 particles/min. We synthesized poly(ethylene glycol) diacrylate (PEGDA) hydrogel beads as the deformability model for device validation and performance evaluation. A deformability-activated sorting purity of 88% and an average efficiency of 73% were achieved. We anticipate that the ability to actively measure and sort individual particles one-by-one in a continuous flow would find applications in cell-mechanotyping studies such as correlational studies of the cell mechanical phenotype and molecular mechanism.

Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa

Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA)—poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e. they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality.

A glycidyl methacrylate modified collagen/polyethylene glycol diacrylate hydrogel: a mechanically strong hydrogel for loading levofloxacin

Artificial suturing of incision after ocular trauma is very complicated and is prone to infection.

3D Printed Hydrogel Multiassay Platforms for Robust Generation of Engineered Contractile Tissues.

We present a method for reproducible manufacture of multiassay platforms with tunable mechanical properties for muscle tissue strip analysis. The platforms result from stereolithographic 3D printing of low protein-binding poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Contractile microtissues have previously been engineered by immobilizing suspended cells in a confined hydrogel matrix with embedded anchoring cantilevers to facilitate muscle tissue strip formation. The 3D shape and mechanical properties of the confinement and the embedded cantilevers are critical for the tissue robustness. High-resolution 3D printing of PEGDA hydrogels offers full design freedom to engineer cantilever stiffness, while minimizing unwanted cell attachment. We demonstrate the applicability by generating suspended muscle tissue strips from C2C12 mouse myoblasts in a compliant fibrin-based hydrogel matrix. The full design freedom allows for new platform geometries that reduce local stress in the matrix and tissue, thus, reducing the risk of tissue fracture.

Bio-inspired anisotropic polymeric heart valves exhibiting valve-like mechanical and hemodynamic behavior

Native heart valve leaflets with layered fibrous structures show anisotropic characteristics, allowing them to withstand complex mechanical loading for long-term cardiac cycles. Herein, two types of silk fibroin (SF) fiber membranes with anisotropic (ASF) and isotropic (ISF) properties were prepared by electrospinning, and were further combined with poly(ethylene glycol) diacrylate (PEGDA) hydrogels to serve as polymeric heart valve (PHV) substitutes (PEGDA-ASF and PEGDA-ISF). The uniaxial tensile tests showed obvious anisotropy of PEGDA-ASF with elastic moduli of 10.95±1.09 and 3.55± 0.32 MPa, respectively, along the directions parallel and perpendicular to the fiber alignment, while PEGDA-ISF possessed isotropic property with elastic moduli of 4.54± 0.43 MPa. The PHVs from both PEGDA-ASF and PEGDA-ISF presented appropriate hydrodynamic properties from pulse duplicator tests according to the ISO 5840-3 standard. However, finite element analysis (FEA) revealed the anisotropic PEGDA-ASF valve showed a lower maximum principle stress value (2.20 MPa) in commissures during diastole compared with that from the isotropic PEGDA-ISF valve (2.37 MPa). In the fully open state, the bending area of the PEGDA-ASF valve appeared in the belly portion and near the attachment line like native valves, however, which was close to free edges for the PEGDA-ISF valve. The Gauss curvature analysis also indicated that the anisotropic PEGDA-ASF valve can produce appropriate surface morphology by dynamically adjusting the movement of bending area during the opening process. Hence, anisotropy of PHVs with bio-inspired layered fibrous structures played important roles in mechanical and hydrodynamic behavior mimicking native heart valves.

3D Printing of Stem Cell Responsive Ionically-Crosslinked Polyethylene Glycol Diacrylate/ Alginate Composite Hydrogels Loaded with Basic Fibroblast Growth Factor for Dental Pulp Tissue Engineering: A Preclinical Evaluation in Animal Model

The main aim of this study was to develop a 3D printed stem cell-responsive polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) composite hydrogel system (PEGDA/SA) loaded with basic fibroblast growth factor (bFGF) suitable for dental pulp tissue engineering. The PEGDA/SA loaded with bFGF (PEGDA/SA-bFGF) at different concentration ratios were 3D printed via stereolithography (SLA) under optimal processing conditions, followed by ionic crosslinking. The morphological and porous structure of the 3D printed PEGDA/SA-bFGF constructs and release profile of the bFGF were analyzed. The cellular compatibility of the hydrogel constructs was evaluated using human dental pulp stem cells (hDPSCs)in vitro. Subsequently, biocompatibility and tissue regenerative potential of the hydrogel constructs were evaluated in immunodeficient mice model. The in vitro cell culture results of PEGDA/SA-bFGF constructs exhibited high cell compatibility and supported cell proliferation, irrespective of their concentration ratios. Thein vivo animal experiment results showed that the hDPSCs-laden PEGDA/SA (PEGDA/SA-hDPSCs) group failed to form a good pulp structure even at various concentration ratios. When the mass ratio of PEGDA/SA was 25:1, hDPSCs-laden PEGDA/SA-bFGF (PEGDA/SA-bFGF-hDPSCs) group also failed to form dental pulp-like tissue but a partial loose connective tissue formation was observed. However, when the mass ratio of PEGDA/SA reduces to 20:1 ~ 15:1, the PEGDA/SA-bFGF-hDPSCs group tends to form a well-organized pulp structure post 4 weeks implantation, thus highlighting the potential of this particular hydrogel scaffolding system for dental pulp tissue regenerative applications.

Microbe Encapsulation for Selective Rare-Earth Recovery from Electronic Waste Leachates.

Rare earth elements (REEs) are indispensable components of many green technologies and of increasing demand globally. However, refining REEs from raw materials using current technologies is energy intensive and enviromentally damaging. Here, we describe the development of a novel biosorption-based flow-through process for selective REE recovery from electronic wastes. An Escherichia coli strain previously engineered to display lanthanide-binding tags on the cell surface was encapsulated within a permeable polyethylene glycol diacrylate (PEGDA) hydrogel at high cell density using an emulsion process. This microbe bead adsorbent contained a homogenous distribution of cells whose surface functional groups remained accessible and effective for selective REE adsorption. The microbe beads were packed into fixed-bed columns, and breakthrough experiments demonstrated effective Nd extraction at a flow velocity of up to 3 m/h at pH 4-6. The microbe bead columns were stable for reuse, retaining 85% of the adsorption capacity after nine consecutive adsorption/desorption cycles. A bench-scale breakthrough curve with a NdFeB magnet leachate revealed a two-bed volume increase in breakthrough points for REEs compared to non-REE impurities and 97% REE purity of the adsorbed fraction upon breakthrough. These results demonstrate that the microbe beads are capable of repeatedly separating REEs from non-REE metals in a column system, paving the way for a biomass-based REE recovery system.

Controlling Fluid Diffusion and Release through Mixed-Molecular-Weight Poly(ethylene) Glycol Diacrylate (PEGDA) Hydrogels.

Due to their inherent ability to swell in the presence of aqueous solutions, hydrogels offer a means for the delivery of therapeutic agents in a range of applications. In the context of designing functional tissue-engineering scaffolds, their role in providing for the diffusion of nutrients to cells is of specific interest. In particular, the facility to provide such nutrients over a prolonged period within the core of a 3D scaffold is a critical consideration for the prevention of cell death and associated tissue-scaffold failure. The work reported here seeks to address this issue via fabrication of hybrid 3D scaffolds with a component fabricated from mixed-molecular-weight hydrogel formulations capable of storing and releasing nutrient solutions over a predetermined time period. To this end, poly(ethylene) glycol diacrylate hydrogel blends comprising mixtures of PEGDA-575 Mw and PEGDA-2000 Mw were prepared via UV polymerization. The effects of addition of the higher-molecular-weight component and the associated photoinitiator concentration on mesh size and corresponding fluid permeability have been investigated by diffusion and release measurements using a Theophylline as an aqueous nutrient model solution. Fluid permeability across the hydrogel films has also been determined using a Rhodamine B solution and associated fluorescence measurements. The results indicate that addition of PEGDA-2000 Mw to PEGDA-575 Mw coupled with the use of a specific photoinitiator concentration provides a means to change mesh size in a hydrogel network while still retaining an overall microporous material structure. The range of mesh sizes created and their distribution in a 3D construct provides for the conditions required for a more prolonged nutrient release profile for tissue-engineering applications.

Digital Maskless Photolithographic Patterning of DNA-Functionalized Poly(ethylene glycol) Diacrylate Hydrogels with Visible Light Enabling Photodirected Release of Oligonucleotides.

Soft biomaterials possessing structural hierarchy have growing applications in lab-on-chip devices, artificial tissues, and micromechanical and chemomechanical systems. The ability to integrate sets of biomolecules, specifically DNA, within hydrogel substrates at precise locations could offer the potential to form and modulate complex biochemical processes with DNA-based molecular switches in such materials and provide a means of creating dynamic spatial patterns, thus enabling spatiotemporal control of a wide array of reaction-diffusion phenomena prevalent in biological systems. Here we develop a means of photopatterning two-dimensional DNA-functionalized poly(ethylene glycol) diacrylate (PEGDA) hydrogel architectures with an aim toward these applications. While PEGDA photopatterning methods are well-established for the fabrication of hydrogels, including those containing oligonucleotides, the photoinitiators typically used have significant crosstalk with many UV-photoswitchable chemistries including nitrobenzyl derivatives. We demonstrate the digital photopatterning of PEGDA-co-DNA hydrogels using a blue light-absorbing (470 nm peak) photoinitiator system and macromer comprised of camphorquinone, triethanolamine, and poly(ethylene glycol) diacrylate (Mn = 575) that minimizes absorption in the UV-A wavelength range commonly used to trigger photoswitchable chemistries. We demonstrate this method using digital maskless photolithography within microfluidic devices that allows for the reliable construction of multidomain structures. The method achieves feature resolutions as small as 25 μm, and the resulting materials allow for lateral isotropic bulk diffusion of short single-stranded (ss) DNA oligonucleotides. Finally, we show how the use of these photoinitiators allows for orthogonal control of photopolymerization and UV-photoscission of acrylate-modified DNA containing a 1-(2-nitrophenyl) ethyl spacer to selectively cleave DNA from regions of a PEGDA substrate.

Hybrid Laser Printing of 3D, Multiscale, Multimaterial Hydrogel Structures.

Fabrication of multiscale, multi-material three-dimensional (3D) structures at high resolution is difficult using current technologies. This is especially significant when working with hydrated and mechanically weak hydrogel materials. In this work, a new hybrid laser printing (HLP) technology is reported to print complex, multiscale, multimaterial, 3D hydrogel structures with microscale resolution. This technique of fabrication utilizes sequential additive and subtractive modes of material fabrication, that are typically considered as mutually exclusive due to differences in their material processing conditions. Further, compared to current laser writing systems that enforce stringent processing depth limits, HLP is shown to fabricate structures at any depth inside the material. As a proof-of-principle, a Mayan Pyramid with embedded cube-frame is printed using model synthetic polyethylene glycol diacrylate (PEGDA) hydrogel. Printing of ready-to-use open-well chips with embedded microchannels is also demonstrated using PEGDA and gelatin methacrylate (GelMA) hydrogels for potential applications in biomedical sciences. Next, HLP is used in additive and additive modes to print multiscale 3D structures spanning in size from centimeter to micrometers within minutes, which is followed by printing of 3D, multi-material, multiscale structures using this technology. Overall, this work demonstrates that HLP's fabrication versatility can potentially offer a unique opportunity for a range of applications in optics and photonics, biomedical sciences, microfluidics, soft robotics, etc.

Keratinocytes maintain compartmentalization between dermal papilla and fibroblasts in 3D heterotypic tri-cultures.

ObjectivesReproducing human hair follicles in vitro is often limited by various reasons such as the lack of a systematic approach to culture distinct hair follicle cell types to reproduce their spatial relationship. Here, we reproduce hair follicle‐like constructs resembling the spatial orientation of different cells in vivo, to study the role of keratinocytes in maintaining cellular compartmentalization among hair follicle‐related cells.Materials and methodsDermal papilla (DP) cells, HaCaT keratinocytes and human dermal fibroblast (HDF) cells were seeded sequentially into three‐dimensional (3D) microwells fabricated from polyethylene glycol diacrylate hydrogels. Quantitative polymerase chain reaction was used to compare inductive gene expression of 3D and two‐dimensional (2D) DP. DP and HaCaT cells were transfected with green fluorescent protein and red fluorescent protein lentivirus, respectively, to enable cell visualization using confocal microscopy. ResultsThe 3D DP cultures showed significantly enhanced expression of essential DP genes as compared 2D cultures. Core‐shell configurations containing keratinocytes forming the outer shell and DP forming the core were observed. Migratory polarization was mediated by cell‐cell interaction between the keratinocytes and HDF cells, while preserving the aggregated state of the DP cells.ConclusionsKeratinocytes may play a role in maintaining compartmentalization between the DP and the surrounding HDF residing in the dermis, and therefore maintains the aggregative state of the DP cells, necessary for hair follicle development and function.

Transient-State Rheological Behavior of Poly(ethylene glycol) Diacrylate Hydrogels at High Shear Strain Rates

Transient rheological properties of poly(ethylene glycol) diacrylate (PEGDA) hydrogels under Couette flow conditions are determined via molecular dynamics simulations and validated by high strain r...

Characterization and optimization of a positively charged poly (ethylene glycol)diacrylate hydrogel as an actuating muscle tissue engineering scaffold.

Hydrogels have been used for many applications in tissue engineering and regenerative medicine due to their versatile material properties and similarities to the native extracellular matrix. Poly (ethylene glycol) diacrylate (PEGDA) is an ionic electroactive polymer (EAP), a material that responds to an electric field with a change in size or shape while in an ionic solution, that may be used in the development of hydrogels. In this study, we have investigated a positively charged EAP that can bend without the need of external ions. PEGDA was modified with the positively charged molecule 2-(methacryloyloxy)ethyl-trimethylammonium chloride (MAETAC) to provide its own positive ions. This hydrogel was then characterized and optimized for bending and cellular biocompatibility with C2C12 mouse myoblast cells. Studies show that the polymer responds to an electric field and supports C2C12 viability.

Digital Light Processing-Based 3D Printing of Cell-Seeding Hydrogel Scaffolds with Regionally Varied Stiffness.

Cell-seeding heterogeneous scaffolds with regionally varied stiffness play an important role in tissue engineering, e.g., bone and cartilage regeneration, that require the recapitulation of geometric complexity through biocompatible material to mimic the natural cell microenvironment in vivo. Here, we report the digital light processing (DLP)-based 3D printing of cell-seeding hydrogel scaffold with regionally varied stiffness by tuning the exposure time without changing the geometric architecture. Mechanical tests on printed poly(ethylene glycol) diacrylate (PEGDA) hydrogels homogeneous scaffold revealed that a 60% increase in the elastic modulus can be achieved by setting the optimal exposure time. Furthermore, regulating the stiffness by varying the exposure time was demonstrated in the printed three-sectional heterogeneous scaffolds. Uniaxial compression tests showed that no fracture was observed even when the compression strain reached up to 25%, indicating that by adjusting the exposure time, the undesired influence of the scaffold on mechanical integrity could be avoided. 3T3 fibroblasts were then seeded onto the scaffold, and the biocompatibility together with the physical support of the scaffolds were confirmed by observation and cell population assessment.

Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing

IntroductionWe previously demonstrated that insulin secreting cells (ISCs) accelerate healing of chronic wounds, and it is known that mesenchymal stem cells (MSCs) also accelerate wound healing. Here, we report that the combination of both cell types coencapsulated into a synthetic hydrogel dressing accelerates chronic wound healing 3 × faster than control and 2 × faster than each cell type delivered singly. Specifically, insulin released by ISCs activates the PI3/Akt pathway, which is vital to the function and survival of MSCs. MSCs in turn improve the viability and function of ISCs.Materials and MethodsMSCs and/or rat islet tumor RIN-m cells were encapsulated into polyethylene glycol diacrylate hydrogel sheets and applied to 1 cm2 full thickness excisional wounds on the dorsa of genetically diabetic male mice (BKS.Cg-m +/+Leprdb/J) in accordance with protocols approved by the Rutgers IACUC. Encapsulated cell viability was assessed using a LIVE/DEAD® Viability/Cytotoxicity Kit. Akt phosphorylation, insulin, VEGF, and TGF-β1 secretion were assessed by ELISA. Animals were sacrificed on postoperative days 14 and 28 and wound tissue was collected for histological and western blot analysis.ResultsISC:MSC combination groups had the highest levels of every secreted product and phosphorylated Akt, and closed wounds in 14 days, ISC-only or MSC-only groups closed wounds in 28 days, control groups closed wounds in 40 days. Further, ISC:MSC groups healed without intermediate scab or scar.ConclusionsCombining MSCs with ISCs results in a more robust healing response than singly delivered cells, warranting further investigation of coencapsulation for MSC therapies.

Hydrophobic-force-driven adsorption of bisphenol A from aqueous solution by polyethylene glycol diacrylate hydrogel microsphere.

Polyethylene glycol diacrylate (PEGDA) hydrogel microsphere was synthesized by UV-assisted reverse emulsion polymerization as an efficient adsorbent for water purification. Optical microscopy and TEM proved its spherical and hollow structure, while XRD pattern proved that it was amorphous with limited crystallinity. Abundant oxygen-containing functional groups such as hydroxyl were detected by FTIR. The hydrogels exhibited low swelling capacities ranging from 0.19 to 0.77g/g in water and would decrease in salty solutions. The effects of operation parameters on the bisphenol A (BPA) adsorption were studied, including the polymer composition between PEGDA and polyethylene glycol methacrylate (PEGMA), initial concentration of BPA, pH, and operation temperature. The resulting hydrogel, especially for PDM2 (the ratio between PEGDA and PEGMA is 2), was able to effectively enrich BPA in water. The adsorption capacity was nearly stable below pH8.0 and decreased when beyond 8.0. Thermodynamic parameters reflected that BPA adsorbed by hydrogel was a spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0) progress. The adsorption capacity increased with the increase of the concentration of NaCl, exhibiting salinity-enhanced adsorption capacity driven by hydrophobic force. Excellent results were also achieved by applying hydrogel for spiked real surface waters, which accounted for more than 91% compared to simulated solution. As-prepared hydrogel was expected to be good candidate for treatment of endocrine disruptors with lower solubility in water.

Engineering functional hydrogel microparticle interfaces by controlled oxygen-inhibited photopolymerization

Functional poly(ethylene glycol) diacrylate (PEGDA) hydrogel microparticles for the detection of bioactive macromolecules were fabricated via oxygen-inhibited photopolymerization in a droplet microfluidic device. Hydrogel network functionalization and architecture were characterized using a biotin-avidin binding assay, which revealed radial network inhomogeneities dependent on exposure conditions. Empirical results were corroborated using a reaction-diffusion model, describing the effects of exposure intensity on the spatial photopolymerization kinetics and resulting polymeric mesh network. The combination of finely controlled exposure conditions and predictive simulations enables the generation of tailored particles with microengineered interfaces and gradients in crosslinking density, which dictate solute diffusivity and elasticity, augmenting the utility of this approach in engineering multifunctional, size-excluding hydrogel particles for multiplexed biomolecular sensing.

Photo-Cross-Linked Poly(ethylene glycol) Diacrylate Hydrogels: Spherical Microparticles to Bow Tie-Shaped Microfibers.

Bow tie-shaped fibers and spherical microparticles with controlled dimensions and shapes were fabricated with poly(ethylene glycol) diacrylate hydrogel utilizing hydrodynamic shear principles and a photopolymerization strategyunder a microfluidic regime. Decreasing the flow rate ratio between the core and sheath fluids from 25 (50:2) to 1.25 (100:80) resulted in increasing the particles size and reducing the production rate by 357 and 86%, respectively. The width of the fibers increased by a factor of 1.4 when the flow rate ratio was reduced from 2.5 to 1 due to the decrease of the shear force at the fluid/fluid interface. The stress at break and Young's modulus of the fibers were enhanced by 32 and 63%, respectively, when the sheath-to-core flow rate ratio decreased from 100:40 to 100:80. The fiber fabrication was simulated using the finite element method, and the numerical and experimental results were in agreement. Adult hippocampal stem/progenitor cells and bone-marrow-derived multipotent mesenchymal stromal cells were seeded onto the fibrous scaffolds in vitro, and cellular adhesion, proliferation, and differentiation were investigated. Microgrooves on the fibers' surface were shown to positively affect cell adhesion when compared to flat fibers and planar controls.