Our overall intent is to develop improved electrically active prostheticdevices to allow interactions between regenerated nerve fibers (axons) andexternal electronics. To allow for infiltration of axons, these devices mustbe highly porous. Additionally, they must exhibit selective and structuredconductivity to allow the connection of electrode sites with externalcircuitry with tunable electrical properties that enable the transmission ofneural signals through physical connections to external circuitry (e.g.through attached wires.) The chosen material must be biocompatible withminimal irresolvable inflammatory response to allow intimate contact withregenerated nerve tissue and mechanically compatible with the surroundingnervous tissue.

We have utilized electrospinning and projection lithography as tools tocreate conductive, porous networks of non-woven biocompatible fibers inorder to meet the materials requirements for the neural interface. Thebiocompatible fibers were based on the known biocompatible materialpoly(dimethyl siloxane) (PDMS) as well as a newer biomaterial materialdeveloped in our laboratories, poly(butylene fumarate) (PBF). Both of thepolymers cannot be electrospun using conventional electrospinning techniquesdue to their low glass transition temperatures, so in situcrosslinking methodologies were developed to facilitate micro- andnano-fiber formation during electrospinning. The conductivity of theelectrospun fiber mats was controlled by varying the loading withmulti-walled carbon nanotubes (MWNTs).

We designed and produced pure cubic zirconia (ZrO2) ceramic1coatings by an ion beam assisted deposition (IBAD) with nanostructurescomparable to the size of proteins. Our ceramic coatings exhibit highhardness and a zero contact angle with serum. In contrast to hydroxyapatite(HA), nano-engineered zirconia films possess excellent adhesion to allorthopaedic materials. Cell adhesion and proliferation experiments wereperformed with a bona fide mesenchymal stromal cell line (OMA-AD). Ourexperimental results indicate that the nano-engineered cubic zirconia issuperior in supporting growth, adhesion, and proliferation. Since cellattachment is mediated by adhesive proteins such as fibronectin (FN), toelucidate why cells attach more effectively to our nanostructures, weperformed a comparative analysis of adsorption energies of FN fragment usingquantum mechanical calculations and Monte Carlo (MC) simulation both onsmooth and nanostructured surfaces. We have found that a FN fragment adsorbssignificantly stronger on the nanostructured surface than on the smooth surface2.

Core-shell PLLA microparticles were successfully fabricated using a novelcoaxial nozzle design. These particles were synthesized with differentcomponents in the core/shell layers representing three classes of systems ofinterest for drug delivery applications: PVA/PLLA, PLLA/PEG, and oleicacid/PLLA. The components were characterized for their physical propertiesand interfacial energies, and optimal conditions for the operation weredetermined. To facilitate the particle characterization, each phase wasdoped with a different fluorescent dye to aid in the confirmation of acore/shell structure via fluorescence microscopy.

In this work the microstructures of star acrylated poly(ethyleneglycol-co-lactide) (SPELA) with different LA:EG ratios in the aqueoussolution have been simulated via Dissipative Particle Dynamics (DPD)approach at the mesoscale. The system components were coarse-grained intodifferent beads (set of atoms) which moved according to the Newton’sequations of motion integrated via a modified Velocity-Verlet algorithm. Theforce acting on each bead, in a specific cutoff distance (rc),was divided into a conservative force (FC), random force (FR), dissipativeforce (FD), bond force (FS) and bond angle force (FE). The repulsionparameters of the conservative force (αij) were calculated fromthe solubility parameter of the beads, each of which were extracted from anatomistic molecular dynamics simulation (MD). Simulations showed theformation of micelles with lactide and acrylate beads occupied the core andhydrophilic ethylene oxide segments extending through the water to form thecorona. The micelles showed an increasing trend in size and decreasing trendin number density with increase in LA:EG ratio. Results showed that theacrylate density decreased from the center of the micelles to the coresurface although the overall amount of acrylates increased due to theincrease in volume. Furthermore, the running integration number ofacrylate-water beads showed decreasing accessibility of acrylates to waterwith increasing PLA volume fraction.

The ability to control the deposition of mouse embryonic stem cells (mESCs),and mESCs encapsulated in 200-μm diameter alginate microbeads, intocustomized patterns has recently been achieved using laser direct-write(LDW). Gelatin-based LDW was utilized to target and reproducibly depositgroups of cells directly onto receiving substrate surfaces. Live/deadstaining for cell viability and immunocytochemistry for the pluripotencymarker, Oct-4, indicated that transferred mESCs were viable followingtransfer, and maintained an important embryonic stem cell marker,respectively. LDW was further used to print mESCs encapsulated in hydrogelmicrobeads into customized patterns on a single-bead basis. Recent effortshave also achieved patterns of discrete co-cultures of mESCs and breastcancer cells in separate hydrogel microbeads. Altogether, we demonstratedthe feasibility of LDW to print patterns of mESCs and mESC-microbeads forthe biomimetic assembly of engineered cellular constructs and tissuemodels.

The consolidation of a pictorial surface or the removal of undesiredmaterial from the surface of an artifact, are the most important anddelicate operations in the conservation of cultural heritage. In thiscontribution we report on the synthesis and characterization of twoinnovative systems for the cleaning of works of art: i) highly viscouspolymeric dispersions (HVPDs) of poly(vinylalcohol-co-vinyl acetate) random copolymer (PVAc), and ii)chemical gels from acrylamide - N,N’-methylene bisacrylamide, loaded withinnovative aqueous cleaning systems. These systems were prepared,characterized and tested over artistic surfaces, such as wood and canvas.Rheology and FTIR spectroscopy allowed the characterization of thematerials, and provided evidence that the systems allow an efficientcleaning of the substrates, without leaving residues.

Electrospinning is a versatile technique for fabricating three-dimensional(3D) nanofibrous scaffolds and the scaffolds have been found to elicitdesirable cellular behavior for tissue regeneration because the nanofibrousstructures mimic the nanofibrous extracellular matrix (ECM) of biologicaltissues. From the material point of view, the ECM of bone is a nanofibrousnanocomposite consisting of an organic matrix (mainly collagen) andinorganic bone apatite nanoparticles. Therefore, for bone tissue engineeringscaffolds, it is natural to construct nanofibrous nanocomposites having abiodegradable polymer matrix and nanosized bioactive bioceramics. Ourprevious studies demonstrated: (1) electrospun nanocomposite fiber loadedwith calcium phosphate (Ca-P) were osteoconductive and could promoteosteoblastic cell proliferation and differentiation better than pure polymerfibers; (2) The controlled release of recombinant human bone morphogeneticprotein (rhBMP-2) from scaffolds provided the scaffolds with desiredosteoinductivity. In the current investigation, novel bicomponent scaffoldsfor bone tissue engineering were produced using our established dual-sourcedual-power electrospinning technique to achieve both osteoconductivity andosteoinductivity. In the bicomponent scaffolds, one fibrous component waselectrospun Ca-P/PLGA nanocomposite fibers and the other component wasemulsion electrospun PDLLA nanofibers incorporated with rhBMP-2. Throughelectrospinning optimization, both fibers were evenly distributed inbicomponent scaffolds. The mass ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGAfibers in bicomponent scaffolds could be controlled using multiple syringes.The structure and morphology of mono- and bicomponent scaffolds wereexamined. The in vitro release of rhBMP-2 from mono- andbicomponent scaffolds showed different release amount but similar releaseprofile, exhibiting an initial burst release. Blending PDLLA withpolyethylene glycol (PEG) could reduce the initial burst release ofrhBMP-2.

Recently, an inexpensive 3D lithography technique was developed by ProfessorNicholas Fang at the University of Illinois where a projector is used incombination with a Microsoft® PowerPoint presentation to expose the liquidnegative-tone photoresist 1,6-hexanediol diacrylate in a layer-by-layerfashion. Where Professor Fang initially used this method as a teaching tool,we have used the inexpensive 3D printing technique to create 3D structuresof fumarate based polymers. This class of polymers are liquids at roomtemperature which makes them ideal for the projector based lithographytechnique when used in combination with the photoinitiatorbisphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO). Furthermore, thefumarate based materials are biocompatible and are suitable candidates fortissue engineering applications.

We present the key assumptions and results of a newly developed theory inorder to account for the self-consistent cascade effects of counterioncondensation and volume collapse of polyeletrolyte gels. In the presenttheory, the role of the specificity and valency of counterions on the volumetransitions are also treated. These features and the fluctuations of monomerconcentration and local electrolyte charge density are included on top ofthe familiar features of the Flory-Huggins theory and the classical rubberelasticity theory in the previously used Flory-Dusek-Patterson-Tanaka theoryof polyelectrolyte gels. We have computed the swelling equilibria bysatisfying the multicomponent nature of the system and the Donnanequilibria. A few major effects are illustrated in terms of the dependenceof volume transition on the solvent quality, temperature, saltconcentration, valency and specificity of the counterion, and polymer chargedensity. Criteria for the emergence of a reentrant volume transition arealso derived.

When a biomaterial is implanted into the body, blood proteins adsorb on itssurface and subsequently cells adhere via the protein adlayer. Thus, theunderstanding of protein adsorption and conformational change on thebiomaterial surfaces is of great importance to control the biocompatibilitysuch as antithrombotic properties and cell adhesion behaviors. In thisstudy, we synthesized hydroxyapatite (HAp) and carbonate apatite (CAp) by awet method. Then we successfully fabricated the HAp and CAp sensors forQCM-R by an electrophoretic deposition method. Adsorption behavior ofproteins on the bone substitute material can be monitored by using theseapatite sensors. Bovine serum albumin and fibrinogen were employed for themodel proteins, and monitored the adsorption behavior on the HAp, CAp andreference gold (Au) sensors by the QCM-R technique. As a result, we revealedthat fibrinogen and bovine serum albumin adsorbs on the gold surface byhydrophobic interaction, and adsorbs on the HAp and CAp surfaces mainly byelectrostatic force. Besides, we revealed that fibrinogen adsorbs on the Ausurface more rigid than on the HAp and CAp surfaces while bovine serumalbumin adsorbs on the HAp and CAp surface more rigidly than on the Ausurface.

Mechanical cues in cellular microenvironment are central in directing aclass of cellular behaviors such as the dynamic of cell adhesion, migration,and differentiation. Several advanced optical techniques, such asstructured-illumination nano-profilometry (SINAP), have been developed for abetter resolution of these dynamic processes. These techniques howeverrequire culturing cells on materials of refractive index close to that ofglass, while most studies regarding the effects of mechanical cues oncellular dynamics were conducted on hydrogel-based substrates. Here wereport the development of culturing substrates of tunable rigidity andrefractive index suitable for SINAP studies. Polyvinyl chloride (PVC)-basedsubstrates were mixed with a softener called Di(isononyl)Cyclohexane-1,2-Dicarboxylate (DINCH) and cured by heating. The volumeratios of PVC to DINCH were varied from 1:1 to 3:1. The Young’s modulus ofthe resulting substrates ranged from 18 kPa to 40 kPa. The yieldedrefractive indices of the composite substrates as measured by phase contrasttomography ranged from 1.47 to 1.53. Human lung adenocarcinoma cells CL1-5were cultured on the composite substrates and cell viability was examinedusing the MTT assay. The dynamics of cell adhesion and filopodia activitieswere examined using SINAP. Preliminary results suggest that PVC basedculturing substrates have a great potential in the application of SINAPbased studies.

Toward complete artificial photosynthesis systems to generate hydrogen andoxygen using visible light and water, we firstly design and fabricateoxygen-generating gel systems using the electrostatic interactions of ionicfunctional groups and steric effects of a polymer network. By using a graftpolymer chain with Ru(bpy)32+ units as sensitizers to closely arrange RuO2nanoparticles as catalyst, the functional groups transmit multiple electronscooperatively to generate oxygen. In this study, a novel strategy is shownto design a hierarchical network structure using colloidal nanoparticles andmacromonomers.

DNA is an anionic polyelectrolyte, which occupies a large volume in saltfree solution due to the coulomb repulsion between the charged groups. Inthe presence of high valence cations, DNA condenses into nanoparticles. DNAnanoparticles have generated a lot of interest as a preferred vehicle fordelivering therapeutic DNA in gene therapy. The efficiency of gene deliveryis determined by stability and compactness of the particles. However notmuch is known about the organization of DNA within the particles. The largepolymer cations condense DNA rapidly, with no distinct intermediate stagesthat give insight into the arrangement of DNA within the nanoparticle. Inour work, we form nanoparticles with short DNA strands to slow down thecondensation process. The polymer cation is polyethyleneimine with graftedsugar moieties. Distinct intermediate stages are observed with Atomic ForceMicroscopy. The assembly occurs via the formation of fiber condensates,which appear to be the unit of DNA condensation. Nanoparticles form bycompaction of interweaving networks of fiber condensates.

Natural and synthetic hydroxyapatite (HA) scaffolds for potentialload-bearing bone implants were fabricated by two methods. The naturalscaffolds were formed by heating bovine cancellous bone at 1325°C, whichremoved the organic and sintered the HA. The synthetic scaffolds wereprepared by freeze-casting HA powders, using different solid loadings (20–35vol.%) and cooling rates (1–10°C/min). Both types of scaffolds wereinfiltrated with polymethylmethacrylate (PMMA). The porosity, pore size, andcompressive mechanical properties of the natural and synthetic scaffoldswere investigated and compared to that of natural cortical and cancellousbone. Prior to infiltration, the sintered cancellous scaffolds exhibitedpore sizes of 100 – 300 μm, a strength of 0.4 – 9.7 MPa, and a Young’smodulus of 0.1 – 1.2 GPa. The freeze-casted scaffolds had pore sizes of 10 –50 μm, strengths of 0.7 – 95.1 MPa, and Young’s moduli of 0.1 –19.2 GPa.When infiltrated with PMMA, the cancellous bone- PMMA composite showed astrength of 55 MPa and a Young’s modulus of 4.5 GPa. Preliminary data forthe synthetic HA-PMMA composite showed a strength of 42 MPa and a modulus of0.8 GPa.

A synthetic strategy to couple selectively an ionic complementary thiolmodified octapeptide, that is able to gel at low temperature, to thethermoresponsive polymer poly(N-isopropylacrylamide) (pNIPAAm) withcontrolled molecular weight and narrow polydispersity is described. Thepolymer was synthesized by atom transfer radical polymerization (ATRP)affording halogen functionalized chain ends. This allowed subsequentcoupling to a thiol terminated ionic complementary octapeptide via nucleophile substitution. Results indicated that thepeptide was covalently attached to the polymer and that both thecoil-globule phase transition of pNIPAAm and the gelation properties of thepeptide were retained in the conjugated product. This method provides aversatile route for the synthesis of a range of bioconjugate materials withcontrolled architecture and dual self-assembling and thermoresponsivebehavior.

High performance polymer network gels consisting of tetra-armpoly(ethyleneglycol) (Tetra-PEG) gels were fabricated via a moduleassembling method and their mechanical properties and structure wereinvestigated by stretching and compression measurements, dynamic mechanicalmeasurements, and small-angle neutron scattering (SANS). It was found thatTetra-PEG gels are nearly-ideal polymer network with negligible fractions ofdefects and entanglements. SANS intensity functions indicated that thenetwork structure was uniform free from spatial inhomogeneities. It isdeduced that this uniform structure is ascribed to its unique preparationmethod, i.e., module assembling method (cross-end-coupling oftetra-functional macromers with complementary functional groups).Characteristic properties originated from the near-ideality as polymernetworks are demonstrated, including its application to ion gels, i.e.,polymer network in ionic liquid.

Bisphosphonate (Bp) was adsorbed on the surface of crystalline calciumphosphates (CP); hydroxyapatite (HAp), octacalcium phosphate (OCP) andDicalcium phosphate dehydrate (DCPD). The amount of Bp adsorbed was thelargest for DCPD per unit surface area, while the amount was the largest forHAp per unit weight. The composites of Bp and amorphous calcium phosphate(ACP) were synthesized by titrating calcium acetate solution into phosphatebuffer solution containing Bp. The amount of Bp doped in the composites was366 μg / mg and was approximately 7 times larger than those of Bp adsorbedon the crystalline Calcium phosphates. TG-DTA measurements of a Bp-calciumand the composite indicated exothermic peaks due to Bp combustion, of whichtemperature were shifted to higher temperature for the composite. Bp in thecomposites was gradually released into phosphate buffered saline, while Bpwas rapidly released into acetate buffer solution accompanied with thedissolution of ACP. This result suggests that the composite of Bp and ACPhas potential for a drug-carrier releasing Bp in response to the conditionof osteoclastic bone resorption.

The art and science of using biological tissue grafts from animal and humansources for various ailments is nascent. Various research groups around theworld are actively investigating the potential prostheses of biologicalorigin. Biological tissue grafts are rendered acellular through variousmethods of processing and fabrication before they are used for the specificpurpose. The remainder is a scaffold that offers framework for host cellularrepopulation and revascularization. Different methods of fixation have beenexplored over several decades to render the biological grafts suitable foruse with or without extraction of cells. Therefore, methods such asglutaraldehyde and polyepoxide crosslinking treatments and dye-mediatedphotooxidation have been developed to stabilize and deantigenize the tissuewhile attempting to maintain its natural mechanical properties. Also,residual cellular components in a bioprosthetic material have beenassociated with undesired effects, such as calcification and immunologicalrecognition, and thus have been the motivation for various decellularizationprocesses. The effects of these stabilization and decellularizationtreatments on mechanical, biological and chemical properties of treatedtissues have been investigated, specifically with regard to calcification,immunogenicity, and cytotoxicity concerns. Naturally derived biologicalscaffolds offer many mechanical, chemical and biological advantages oversynthetic materials, and thus hold tremendous potential for use in tissueengineering therapies. Therefore the rationale of using biological grafts inusable forms is gaining importance in order to avoid unwanted chronicinflammatory reactions. This review article discusses the need for suchbioprosthetics and the potential role for natural tissues in variousapplications.

Poly(N-isopropylacrylamide) (PNIPAM), a classic thermo-sensitive polymer,has a lower critical solution temperature (LCST) at ∼32°C. In this work wehave used molecular dynamics simulations to understand the origin of theLCST and agglomeration of PNIPAM chains of 5 and 30 monomer units (5-mer and30-mer). Experimentally, when the concentration of PNIPAM is >1 ppm,polymer chains after undergoing coil-to-globule transition above the LCSTaggregates to yield a stable colloidal dispersion.In our study two PNIPAMchains, consisting of 30 monomer units each, were placed in a cubicsimulation cell and were subsequently solvated. Simulations were carried outbelow and above the LCST, namely at 278 and 310K for 10ns. Simulatedtrajectories were analyzed for structural and dynamical properties of bothPNIPAM and water. We observe coil-to-globule transition in PNIPAM above theLCST. We also find that the PNIPAM chains agglomerate above the LCST. Wealso observe entanglement in PNIPAM chains below the LCST. We also studyagglomeration of 5 PNIPAM chains each consisting of 5 monomer units. Therewas no significant difference in polymer agglomeration behavior across theLCST for these short chain oligomers. The agglomeration behavior is thusstrongly correlated to the size of the polymer chains. These results providefundamental insight into the atomistic scale mechanism of PNIPAMagglomeration across the LCST.