Yong Mei Chen

Recent advances in synthesis and surface modification of lanthanide-doped upconversion nanoparticles for biomedical applications

Lanthanide (Ln)-doped upconversion nanoparticles (UCNPs) with appropriate surface modification can be used for a wide range of biomedical applications such as bio-detection, cancer therapy, bio-labeling, fluorescence imaging, magnetic resonance imaging and drug delivery. The upconversion phenomenon exhibited by Ln-doped UCNPs renders them tremendous advantages in biological applications over other types of fluorescent materials (e.g., organic dyes, fluorescent proteins, gold nanoparticles, quantum dots, and luminescent transition metal complexes) for: (i) enhanced tissue penetration depths achieved by near-infrared (NIR) excitation; (ii) improved stability against photobleaching, photoblinking and photochemical degradation; (iii) non-photodamaging to DNA/RNA due to lower excitation light energy; (iv) lower cytotoxicity; and (v) higher detection sensitivity. Ln-doped UCNPs are therefore attracting increasing attentions in recent years. In this review, we present recent advances in the synthesis of Ln-doped UCNPs and their surface modification, as well as their emerging applications in biomedicine. The future prospects of Ln-doped UCNPs for biomedical applications are also discussed.

Strengthening Alginate/Polyacrylamide Hydrogels Using Various Multivalent Cations

We successfully synthesized a family of alginate/polyacrylamide hydrogels using various multivalent cations. These hydrogels exhibit exceptional mechanical properties. In particular, we discovered that the hydrogels cross-linked by trivalent cations are much stronger than those cross-linked by divalent cations. We demonstrate stretchability and toughness of the hydrogels by inflating a hydrogel sheet into a large balloon, and the elasticity by using a hydrogel block as a vibration isolator in a forced vibration test. The excellent mechanical properties of these hydrogels may open up applications for hydrogels.

Microfluidic hydrogels for tissue engineering.

With advanced properties similar to the native extracellular matrix, hydrogels have found widespread applications in tissue engineering. Hydrogel-based cellular constructs have been successfully developed to engineer different tissues such as skin, cartilage and bladder. Whilst significant advances have been made, it is still challenging to fabricate large and complex functional tissues due mainly to the limited diffusion capability of hydrogels. The integration of microfluidic networks and hydrogels can greatly enhance mass transport in hydrogels and spatiotemporally control the chemical microenvironment of cells, mimicking the function of native microvessels. In this review, we present and discuss recent advances in the fabrication of microfluidic hydrogels from the viewpoint of tissue engineering. Further development of new hydrogels and microengineering technologies will have a great impact on tissue engineering.

Tough Al-alginate/Poly(N-isopropylacrylamide) Hydrogel with Tunable LCST for Soft Robotics

Tough Al-alginate/poly(N-isopropylacrylamide) (PNIPAM) hydrogel has been synthesized by introducing an interpenetrating network with hybrid physically cross-linked alginate and chemically cross-linked PNIPAM. Varying the concentration of AlCl3 regulates the mechanical properties of the tough hydrogel and tunes its lower critical solution temperature (LCST) as well. The tough Al-alginate/PNIPAM exhibits 6.3 ± 0.3 MPa of compressive stress and 9.95 of uniaxial stretch. Tunability of LCST is also achieved in a wide range within 22.5-32 °C. A bending beam actuator and a four-arm gripper made of bilayer (Na-alginate/PNIPAM)/(Al-alginate/PNIPAM) hydrogel as prototype of all-hydrogel soft robotics are demonstrated. A finite element (FE) simulation model is developed to simulate the deformation of the soft robotics. The FE simulation not only reproduces the deformation process of performed experiments but also predicts more complicated devices that can be explored in the future. This work broadens the application of temperature-responsive PNIPAM-based hydrogels.

Highly Stretchable and Transparent Ionogels as Nonvolatile Conductors for Dielectric Elastomer Transducers

Large deformation of soft materials is harnessed to provide functions in the nascent field of soft machines. This paper describes a new class of systems enabled by highly stretchable, transparent, stable ionogels. We synthesize an ionogel by polymerizing acrylic acid in ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate ([C2mim][EtSO4]). The ionogel exhibits desired attributes of adequate conductivity (0.22 S m(-1)), low elastic modulus (∼3 kPa), large rupturing stretch (∼4.6), and negligible hysteresis and degradation after cyclic stretches of large amplitude. Using the ionogel and a dielectric elastomer, we fabricate electromechanical transducers that achieve a voltage-induced areal strain of 140%. The ionogel is somewhat hygroscopic, but the transducers remain stable after a million cycles of excitation in a dry oven and in air. The transparency of the ionogels enable the transducers with conductors placed in the path of light, and the nonvolatility of the ionogels enable the transducers to be used in open air.

Electroluminescence of Giant Stretchability

A new type of electroluminescent device achieves giant stretchability by integrating electronic and ionic components. The device uses phosphor powders as electroluminescent materials, and hydrogels as stretchable and transparent ionic conductors. Subject to cyclic voltage, the phosphor powders luminesce, but the ionic conductors do not electrolyze. The device produces constant luminance when stretched up to an area strain of 1500%.

In vitro differentiation of chondrogenic ATDC5 cells is enhanced by culturing on synthetic hydrogels with various charge densities.

We investigated the behavior of chondrogenic ATDC5 cells on synthetic polymer gels with various charge densities: negatively charged poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) gel, neutral poly(dimethylacrylamide) (PDMAAm) gel, and copolymer gels of 2-acrylamido-2-methyl-1-propanesulfonic acid and dimethylacrylamide P(AMPS-co-DMAAm) with different compositions (molar fractions of AMPS, F=0.25, 0.5, 0.75). In insulin-free maintenance medium, the ATDC5 cells cultured on the highly negatively charged gels - PAMPS gel and the P(AMPS-co-DMAAm) copolymer gels (F=0.75) - spread and became confluent at day 7, and interestingly formed nodules at day 14, expressing type II collagen and proteoglycan. This result demonstrates that the highly negatively charged gels can induce chondrogenic differentiation of ATDC5 cells even in insulin-free maintenance medium, in which the ATDC5 cells cultured on the standard polystyrene dish cannot differentiate into chondrocytes. In insulin-supplemented differentiation medium, ATDC5 cells cultured on the PDMAAm gel made focal adhesions, rapidly aggregated and formed large nodules within 7 days, expressing significantly greater levels of type II collagen and proteoglycan than cells cultured on the polystyrene dish and the negatively charged gels. These results showed that the neutral gel accelerated chondrogenic differentiation of ATDC5 cells cultured in the differentiation medium. We suggest that the highly negatively charged PAMPS gel and the neutral PDMAAm gel are interesting biomaterials for cartilage tissue engineering as a scaffold with the potential to induce chondrogenic differentiation.

Tuning of cell proliferation on tough gels by critical charge effect

Tough triple network (TN) hydrogels that facilitate cell spreading and proliferation and, at the same time, preserve high mechanical strength are synthesized by the introduction of a proper component of negatively charged moiety, poly(2-acrylamido-2-methyl-propane sulfonic acid sodium salt) (PNaAMPS), on which cells proliferate, with neutral moiety, poly(N,N-dimethylacrylamide) (DMAAm), on which cells do not proliferate, as the third network component, to PNaAMPS/PDMAAm double network (DN) gels. For synthesizing the tough TN gels to support cell viability, the effect of charge density on the behaviors of three kinds of cells, bovine fetal aorta endothelial cells (BFAECs), human umbilical endothelial cells (HUVECs), and rabbit synovial tissue-derived fibroblast cells (RSTFCs) were systematically investigated on poly(NaAMPS-co-DMAAm) gels with different charge density. The charge density of the gels was tuned by changing the molar fraction (F) of negatively charged monomer in the copolymer hydrogels. Critical F, which corresponds to a critical value of the zeta potential (zeta), is observed for cell spreading and proliferation. The critical F for BFAECs and HUVECs proliferate to confluent is F = 0.4 (zeta = -20 mV), whereas the critical F for RSTFCs shifts to F = 0.7 (zeta = -28.5 mV). The effect of gel charge density on cell behavior is correlated well with the total adsorbed proteins and fibronectin. By applying these results, cell proliferation is successfully realized on the tough TN hydrogels without surface modification with any cell adhesive proteins or peptides. The results will substantially promote the application of tough hydrogels as soft and wet tissues.

Directed self-assembly of microscale hydrogels by electrostatic interaction

The unique benefit of electrostatic self-assembly of microscale components in solution is demonstrated for the first time. In particular, positive and negative treatment of poly(ethylene glycol) (PEG) facilitates a novel bottom-up assembly approach using electrostatic interaction from microgels with opposite charges. Fundamental investigations of electrostatic interaction of microgels reveal that the contact area of microgels determines the total energy of construct and thus the final patterns. The electrostatic self-assembly approach enables the fabrication of large and complex biological related structures (e.g., multi-layer spheroid) with accurate control. By the design of the microgels, the thickness and number of microgels in each layer can be controlled. Biological investigations of positive and negative treatments of PEG further prove the possibility of using this approach in tissue engineering, regenerative medicine and drug delivery.

Dynamic cell behavior on synthetic hydrogels with different charge densities

A series of poly(NaSS-co-DMAAm) hydrogels with ζ potentials (ζ) in the range −8.8–−20.5 mV and a constant Youngs modulus (E) of ca. 200 kPa were designed for studying the effect of the charge density of hydrogels on dynamic cell behavior. The ζ was adjusted by tuning the molar friction of negatively charged sodium p-styrene sulfonate (NaSS) contained in the monomer mixture [NaSS and N, N-dimethyl acrylamide (DMAAm)] for gelation. A critical ζ potential, which controls cell behavior, ζcrit = −14.0 mV, was observed. When ζ > ζcrit, the cells exhibited a small spreading area, fast migration velocity, and a large migration distance, with concurrent deficiency in actin fibers and less prominent focal adhesions. Conversely, when ζ ≤ ζcrit, the cells exhibited a large spreading area, slow migration velocity, and a short migration distance, with concurrent well-developed actin fibers and prominent focal adhesions. Furthermore, cells repeatedly oscillated in a stick–slip mode from a spreading shape to a round shape on the hydrogels with ζ > ζcrit, although were unable to proliferate. The cell behavior is well correlated with the adsorbed fibronectin on the hydrogel surfaces.