Gerardo Ico

Size-dependent piezoelectric and mechanical properties of electrospun P(VDF-TrFE) nanofibers for enhanced energy harvesting

Piezoelectricity-based energy harvesting from wasted mechanical energies has garnered an increasing attention as a clean energy source. Especially, flexible organic piezoelectric materials provide an opportunity to exploit their uses in mechanically challenging areas where brittle inorganic counterparts have mechanical limitations. In this regard, electrospinning has shown its advantages of producing poly(vinylidene fluoride) (PVDF)-based nanofibrous structures without the necessity of a secondary processing to induce/increase piezoelectric properties. However, the effects of electrospun fiber dimension, one of the main morphological parameters in electrospun fibers, on piezoelectricity have not been fully understood. In this study, two dependent design of experiments (DOEs) were utilized to systematically control the dimensions of electrospun poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) to produce nanofibers having their diameter ranging from 1000 to sub-100 nm. Such a dimensional reduction resulted in the increase of piezoelectric responsible electroactive phase content and the degree of crystallinity. These changes in crystal structure led to approximately 2-fold increase in piezoelectric constant as compared to typical P(VDF-TrFE) thin films. More substantially, the dimensional reduction also increased the Youngs modulus of the nanofibers up to approximately 80-fold. The increases in piezoelectric constant and Youngs modulus collectively enhanced piezoelectric performance, resulting in the exponential increase in electric output of nanofiber mats when the fiber diameters were reduced from 860 nm down to 90 nm. Taken together, the results suggest a new strategy to improve the piezoelectric performance of electrospun P(VDF-TrFE) via optimization of their electromechanical and mechanical properties.

Microstructure-dependent mechanical properties of electrospun core–shell scaffolds at multi-scale levels

Mechanical factors among many physiochemical properties of scaffolds for stem cell-based tissue engineering significantly affect tissue morphogenesis by controlling stem cell behaviors including proliferation and phenotype-specific differentiation. Core-shell electrospinning provides a unique opportunity to control mechanical properties of scaffolds independent of surface chemistry, rendering a greater freedom to tailor design for specific applications. In this study, we synthesized electrospun core-shell scaffolds having different core composition and/or core-to-shell dimensional ratios. Two independent biocompatible polymer systems, polyetherketoneketone (PEKK) and gelatin as the core materials while maintaining the shell polymer with polycaprolactone (PCL), were utilized. The mechanics of such scaffolds was analyzed at the microscale and macroscales to determine the potential implications it may hold for cell-material and tissue-material interactions. The mechanical properties of individual core-shell fibers were controlled by core-shell composition and structure. The individual fiber modulus correlated with the increase in percent core size ranging from 0.55±0.10GPa to 1.74±0.22GPa and 0.48±0.12GPa to 1.53±0.12GPa for the PEKK-PCL and gelatin-PCL fibers, respectively. More importantly, it was demonstrated that mechanical properties of the scaffolds at the macroscale were dominantly determined by porosity under compression. The increase of scaffold porosity from 70.2%±1.0% to 93.2%±0.5% by increasing the core size in the PEKK-PCL scaffold resulted in the decrease of the compressive elastic modulus from 227.67±20.39kPa to 14.55±1.43kPa while a greater changes in the porosity of gelatin-PCL scaffold from 54.5%±4.2% to 89.6%±0.4% resulted in the compressive elastic modulus change from 484.01±30.18kPa to 17.57±1.40kPa. On the other hand, the biphasic behaviors under tensile mechanical loading result in a range from a minimum of 5.42±1.05MPa to a maximum of 12.00±1.96MPa for the PEKK-PCL scaffolds, and 10.19±4.49MPa to 22.60±2.44MPa for the gelatin-PCL scaffolds. These results suggest a feasible approach for precisely controlling the local and global mechanical characteristics, in addition to independent control over surface chemistry, to achieve a desired tissue morphogenesis using the core-shell electrospinning.

Enhanced Lineage-Specific Differentiation Efficiency of Human Induced Pluripotent Stem Cells by Engineering Colony Dimensionality Using Electrospun Scaffolds

Electrospun scaffolds with varied stiffness promote distinct colony morphology of human induced pluripotent stem cells, which affects their subsequent differentiation. On soft scaffolds, induced pluripotent stem cells develop 3D colonies due to the pliability of the electrospun fibrous networks, leading to greater differentiation tendency to ectodermal lineage.

Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells.

Hydrogels have shown great potential for cartilage tissue engineering applications due to their capability to encapsulate cells within biomimetic, 3-dimensional (3D) microenvironments. However, the multi-step fabrication process that is necessary to produce cell/scaffold constructs with defined dimensions, limits their off-the-shelf translational usage. In this study, we have developed a hybrid scaffolding system which combines a thermosensitive hydrogel, poly(ethylene glycol)-poly(N-isopropylacrylamide) (PEG-PNIPAAm), with a biodegradable polymer, poly(ε-caprolactone) (PCL), into a composite, electrospun microfibrous structure. A judicious optimization of material composition and electrospinning process produced a structurally self-supporting hybrid scaffold. The reverse thermosensitivity of PEG-PNIPAAm allowed its dissolution/hydration upon cell seeding within a network of PCL microfibers while maintaining the overall scaffold shape at room temperature. A subsequent temperature elevation to 37 °C induced the hydrogels phase transition to a gel state, effectively encapsulating cells in a 3D hydrogel without the use of a mold. We demonstrated that the hybrid scaffold enhanced chondrogenic differentiation of human mesenchymal stem cells (hMSCs) based on chondrocytic gene and protein expression, which resulted in superior viscoelastic properties of the cell/scaffold constructs. The hybrid scaffold enables a facile, single-step cell seeding process to inoculate cells within a 3D hydrogel with the potential for cartilage tissue engineering. STATEMENT OF SIGNIFICANCE Hydrogels have demonstrated the excellent ability to enhance chondrogenesis of stem cells due to their hydrated fibrous nanostructure providing a cellular environment similar to native cartilage. However, the necessity for multi-step processes, including mixing of hydrogel precursor with cells and subsequent gelation in a mold to form a defined shape, limits their off-the-shelf usage. In this study, we developed a hybrid scaffold by combining a thermosensitive hydrogel with a mechanically stable polymer, which provides a facile means to inoculate cells in a 3D hydrogel with a mold-less, single step cell seeding process. We further showed that the hybrid scaffold enhanced chondrogenesis of mesenchymal stem cells, demonstrating its potential for cartilage tissue engineering.

Lineage- and developmental stage-specific mechanomodulation of induced pluripotent stem cell differentiation

BackgroundTo maximize the translational utility of human induced pluripotent stem cells (iPSCs), the ability to precisely modulate the differentiation of iPSCs to target phenotypes is critical. Although the effects of the physical cell niche on stem cell differentiation are well documented, current approaches to direct step-wise differentiation of iPSCs have been typically limited to the optimization of soluble factors. In this regard, we investigated how temporally varied substrate stiffness affects the step-wise differentiation of iPSCs towards various lineages/phenotypes.MethodsElectrospun nanofibrous substrates with different reduced Young’s modulus were utilized to subject cells to different mechanical environments during the differentiation process towards representative phenotypes from each of three germ layer derivatives including motor neuron, pancreatic endoderm, and chondrocyte. Phenotype-specific markers of each lineage/stage were utilized to determine differentiation efficiency by reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence imaging for gene and protein expression analysis, respectively.ResultsThe results presented in this proof-of-concept study are the first to systematically demonstrate the significant role of the temporally varied mechanical microenvironment on the differentiation of stem cells. Our results demonstrate that the process of differentiation from pluripotent cells to functional end-phenotypes is mechanoresponsive in a lineage- and differentiation stage-specific manner.ConclusionsLineage/developmental stage-dependent optimization of electrospun substrate stiffness provides a unique opportunity to enhance differentiation efficiency of iPSCs for their facilitated therapeutic applications.

Transformative piezoelectric enhancement of P(VDF-TrFE) synergistically driven by nanoscale dimensional reduction and thermal treatment

Despite the significant potential of organic piezoelectric materials in the electro-mechanical or mechano-electrical applications that require light and flexible material properties, the intrinsically low piezoelectric performance as compared to traditional inorganic materials has limited their full utilization. In this study, we demonstrate that dimensional reduction of poly(vinylidene fluoride trifluoroethylene) (P(VDF-TrFE)) at the nanoscale by electrospinning, combined with an appropriate thermal treatment, induces a transformative enhancement in piezoelectric performance. Specifically, the piezoelectric coefficient (d33) reached up to -108 pm V-1, approaching that of inorganic counterparts. Electrospun mats composed of thermo-treated 30 nm nanofibers with a thickness of 15 μm produced a consistent peak-to-peak voltage of 38.5 V and a power output of 74.1 μW at a strain of 0.26% while sustaining energy production over 10k repeated actuations. The exceptional piezoelectric performance was realized by the enhancement of piezoelectric dipole alignment and the materialization of flexoelectricity, both from the synergistic effects of dimensional reduction and thermal treatment. Our findings suggest that dimensionally controlled and thermally treated electrospun P(VDF-TrFE) nanofibers provide an opportunity to exploit their flexibility and durability for mechanically challenging applications while matching the piezoelectric performance of brittle, inorganic piezoelectric materials.

Electrospun Scaffolds: Enhanced Lineage-Specific Differentiation Efficiency of Human Induced Pluripotent Stem Cells by Engineering Colony Dimensionality Using Electrospun Scaffolds (Adv. Healthcare Mater. 12/2016)

Electrospun scaffolds provide soft nanofibrous networks pliable by human induced pluripotent stem cells. J. Nam and co-workers show on page 1408 that such compliant scaffolding leads to the formation of stem cell colonies with a distinctive three-dimensional morphology. The morphological modulation resulted in the lineage-specific differentiation, suggesting a potential means to enhance translational applications of the stem cells.

Effect of capsid proteins to ICG mass ratio on fluorescent quantum yield of virus-resembling optical nano-materials

We recently reported construction of a new type of optical nano-construct composed of genome-depleted plant infecting brome mosaic virus (BMV) doped with Indocyanine green (ICG), an FDA-approved chromophore. We refer to these constructs as optical viral ghosts (OVGs) since only the capsid protein (CP) subunits of BMV remain to encapsulate ICG. To utilize OVGs as effective nano-probes in fluorescence imaging applications, their fluorescence quantum yield needs to be maximized. In this study, we investigate the effect of altering the CP to ICG mass ratio on the fluorescent quantum yield of OVGs. Results of this study provide the basis for construction of OVGs with optimal amounts of CP and ICG to yield maximal fluorescence quantum yield.