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

We have utilized electrospinning and projection lithography as tools to create conductive, porous networks of non-woven biocompatible fibers in order to meet the materials requirements for the neural interface. The biocompatible fibers were based on the known biocompatible material poly(dimethyl siloxane) (PDMS) as well as a newer biomaterial material developed in our laboratories, poly(butylene fumarate) (PBF). Both of the polymers cannot be electrospun using conventional electrospinning techniques due to their low glass transition temperatures, so in situ crosslinking methodologies were developed to facilitate micro- and nano-fiber formation during electrospinning. The conductivity of the electrospun fiber mats was controlled by varying the loading with multi-walled carbon nanotubes (MWNTs).

We designed and produced pure cubic zirconia (ZrO2) ceramic1 coatings by an ion beam assisted deposition (IBAD) with nanostructures comparable to the size of proteins. Our ceramic coatings exhibit high hardness and a zero contact angle with serum. In contrast to hydroxyapatite (HA), nano-engineered zirconia films possess excellent adhesion to all orthopaedic materials. Cell adhesion and proliferation experiments were performed with a bona fide mesenchymal stromal cell line (OMA-AD). Our experimental results indicate that the nano-engineered cubic zirconia is superior in supporting growth, adhesion, and proliferation. Since cell attachment is mediated by adhesive proteins such as fibronectin (FN), to elucidate why cells attach more effectively to our nanostructures, we performed a comparative analysis of adsorption energies of FN fragment using quantum mechanical calculations and Monte Carlo (MC) simulation both on smooth and nanostructured surfaces. We have found that a FN fragment adsorbs significantly stronger on the nanostructured surface than on the smooth surface2.

Core-shell PLLA microparticles were successfully fabricated using a novel coaxial nozzle design. These particles were synthesized with different components in the core/shell layers representing three classes of systems of interest for drug delivery applications: PVA/PLLA, PLLA/PEG, and oleic acid/PLLA. The components were characterized for their physical properties and interfacial energies, and optimal conditions for the operation were determined. To facilitate the particle characterization, each phase was doped with a different fluorescent dye to aid in the confirmation of a core/shell structure via fluorescence microscopy.

In this work the microstructures of star acrylated poly(ethylene glycol-co-lactide) (SPELA) with different LA:EG ratios in the aqueous solution have been simulated via Dissipative Particle Dynamics (DPD) approach at the mesoscale. The system components were coarse-grained into different beads (set of atoms) which moved according to the Newton’s equations of motion integrated via a modified Velocity-Verlet algorithm. The force acting on each bead, in a specific cutoff distance (rc), was divided into a conservative force (FC), random force (FR), dissipative force (FD), bond force (FS) and bond angle force (FE). The repulsion parameters of the conservative force (αij) were calculated from the solubility parameter of the beads, each of which were extracted from an atomistic molecular dynamics simulation (MD). Simulations showed the formation of micelles with lactide and acrylate beads occupied the core and hydrophilic ethylene oxide segments extending through the water to form the corona. The micelles showed an increasing trend in size and decreasing trend in number density with increase in LA:EG ratio. Results showed that the acrylate density decreased from the center of the micelles to the core surface although the overall amount of acrylates increased due to the increase in volume. Furthermore, the running integration number of acrylate-water beads showed decreasing accessibility of acrylates to water with 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, into customized patterns has recently been achieved using laser direct-write (LDW). Gelatin-based LDW was utilized to target and reproducibly deposit groups of cells directly onto receiving substrate surfaces. Live/dead staining for cell viability and immunocytochemistry for the pluripotency marker, Oct-4, indicated that transferred mESCs were viable following transfer, and maintained an important embryonic stem cell marker, respectively. LDW was further used to print mESCs encapsulated in hydrogel microbeads into customized patterns on a single-bead basis. Recent efforts have also achieved patterns of discrete co-cultures of mESCs and breast cancer cells in separate hydrogel microbeads. Altogether, we demonstrated the feasibility of LDW to print patterns of mESCs and mESC-microbeads for the biomimetic assembly of engineered cellular constructs and tissue models.

The consolidation of a pictorial surface or the removal of undesired material from the surface of an artifact, are the most important and delicate operations in the conservation of cultural heritage. In this contribution we report on the synthesis and characterization of two innovative systems for the cleaning of works of art: i) highly viscous polymeric dispersions (HVPDs) of poly(vinyl alcohol-co-vinyl acetate) random copolymer (PVAc), and ii) chemical gels from acrylamide - N,N’-methylene bisacrylamide, loaded with innovative 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 the materials, and provided evidence that the systems allow an efficient cleaning 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 elicit desirable cellular behavior for tissue regeneration because the nanofibrous structures mimic the nanofibrous extracellular matrix (ECM) of biological tissues. From the material point of view, the ECM of bone is a nanofibrous nanocomposite consisting of an organic matrix (mainly collagen) and inorganic bone apatite nanoparticles. Therefore, for bone tissue engineering scaffolds, it is natural to construct nanofibrous nanocomposites having a biodegradable polymer matrix and nanosized bioactive bioceramics. Our previous studies demonstrated: (1) electrospun nanocomposite fiber loaded with calcium phosphate (Ca-P) were osteoconductive and could promote osteoblastic cell proliferation and differentiation better than pure polymer fibers; (2) The controlled release of recombinant human bone morphogenetic protein (rhBMP-2) from scaffolds provided the scaffolds with desired osteoinductivity. In the current investigation, novel bicomponent scaffolds for bone tissue engineering were produced using our established dual-source dual-power electrospinning technique to achieve both osteoconductivity and osteoinductivity. In the bicomponent scaffolds, one fibrous component was electrospun Ca-P/PLGA nanocomposite fibers and the other component was emulsion electrospun PDLLA nanofibers incorporated with rhBMP-2. Through electrospinning optimization, both fibers were evenly distributed in bicomponent scaffolds. The mass ratio of rhBMP-2/PDLLA fibers to Ca-P/PLGA fibers in bicomponent scaffolds could be controlled using multiple syringes. The structure and morphology of mono- and bicomponent scaffolds were examined. The in vitro release of rhBMP-2 from mono- and bicomponent scaffolds showed different release amount but similar release profile, exhibiting an initial burst release. Blending PDLLA with polyethylene glycol (PEG) could reduce the initial burst release of rhBMP-2.

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

We present the key assumptions and results of a newly developed theory in order to account for the self-consistent cascade effects of counterion condensation and volume collapse of polyeletrolyte gels. In the present theory, the role of the specificity and valency of counterions on the volume transitions are also treated. These features and the fluctuations of monomer concentration and local electrolyte charge density are included on top of the familiar features of the Flory-Huggins theory and the classical rubber elasticity theory in the previously used Flory-Dusek-Patterson-Tanaka theory of polyelectrolyte gels. We have computed the swelling equilibria by satisfying the multicomponent nature of the system and the Donnan equilibria. A few major effects are illustrated in terms of the dependence of volume transition on the solvent quality, temperature, salt concentration, valency and specificity of the counterion, and polymer charge density. Criteria for the emergence of a reentrant volume transition are also derived.

When a biomaterial is implanted into the body, blood proteins adsorb on its surface and subsequently cells adhere via the protein adlayer. Thus, the understanding of protein adsorption and conformational change on the biomaterial surfaces is of great importance to control the biocompatibility such as antithrombotic properties and cell adhesion behaviors. In this study, we synthesized hydroxyapatite (HAp) and carbonate apatite (CAp) by a wet method. Then we successfully fabricated the HAp and CAp sensors for QCM-R by an electrophoretic deposition method. Adsorption behavior of proteins on the bone substitute material can be monitored by using these apatite sensors. Bovine serum albumin and fibrinogen were employed for the model proteins, and monitored the adsorption behavior on the HAp, CAp and reference gold (Au) sensors by the QCM-R technique. As a result, we revealed that fibrinogen and bovine serum albumin adsorbs on the gold surface by hydrophobic interaction, and adsorbs on the HAp and CAp surfaces mainly by electrostatic force. Besides, we revealed that fibrinogen adsorbs on the Au surface more rigid than on the HAp and CAp surfaces while bovine serum albumin adsorbs on the HAp and CAp surface more rigidly than on the Au surface.

Mechanical cues in cellular microenvironment are central in directing a class of cellular behaviors such as the dynamic of cell adhesion, migration, and differentiation. Several advanced optical techniques, such as structured-illumination nano-profilometry (SINAP), have been developed for a better resolution of these dynamic processes. These techniques however require culturing cells on materials of refractive index close to that of glass, while most studies regarding the effects of mechanical cues on cellular dynamics were conducted on hydrogel-based substrates. Here we report the development of culturing substrates of tunable rigidity and refractive index suitable for SINAP studies. Polyvinyl chloride (PVC)-based substrates were mixed with a softener called Di(isononyl) Cyclohexane-1,2-Dicarboxylate (DINCH) and cured by heating. The volume ratios of PVC to DINCH were varied from 1:1 to 3:1. The Young’s modulus of the resulting substrates ranged from 18 kPa to 40 kPa. The yielded refractive indices of the composite substrates as measured by phase contrast tomography ranged from 1.47 to 1.53. Human lung adenocarcinoma cells CL1-5 were cultured on the composite substrates and cell viability was examined using the MTT assay. The dynamics of cell adhesion and filopodia activities were examined using SINAP. Preliminary results suggest that PVC based culturing substrates have a great potential in the application of SINAP based studies.

Toward complete artificial photosynthesis systems to generate hydrogen and oxygen using visible light and water, we firstly design and fabricate oxygen-generating gel systems using the electrostatic interactions of ionic functional groups and steric effects of a polymer network. By using a graft polymer chain with Ru(bpy)32+ units as sensitizers to closely arrange RuO2 nanoparticles as catalyst, the functional groups transmit multiple electrons cooperatively to generate oxygen. In this study, a novel strategy is shown to design a hierarchical network structure using colloidal nanoparticles and macromonomers.

DNA is an anionic polyelectrolyte, which occupies a large volume in salt free solution due to the coulomb repulsion between the charged groups. In the presence of high valence cations, DNA condenses into nanoparticles. DNA nanoparticles have generated a lot of interest as a preferred vehicle for delivering therapeutic DNA in gene therapy. The efficiency of gene delivery is determined by stability and compactness of the particles. However not much is known about the organization of DNA within the particles. The large polymer cations condense DNA rapidly, with no distinct intermediate stages that give insight into the arrangement of DNA within the nanoparticle. In our work, we form nanoparticles with short DNA strands to slow down the condensation process. The polymer cation is polyethyleneimine with grafted sugar moieties. Distinct intermediate stages are observed with Atomic Force Microscopy. The assembly occurs via the formation of fiber condensates, which appear to be the unit of DNA condensation. Nanoparticles form by compaction of interweaving networks of fiber condensates.

Natural and synthetic hydroxyapatite (HA) scaffolds for potential load-bearing bone implants were fabricated by two methods. The natural scaffolds were formed by heating bovine cancellous bone at 1325°C, which removed the organic and sintered the HA. The synthetic scaffolds were prepared by freeze-casting HA powders, using different solid loadings (20–35 vol.%) and cooling rates (1–10°C/min). Both types of scaffolds were infiltrated with polymethylmethacrylate (PMMA). The porosity, pore size, and compressive mechanical properties of the natural and synthetic scaffolds were investigated and compared to that of natural cortical and cancellous bone. Prior to infiltration, the sintered cancellous scaffolds exhibited pore sizes of 100 – 300 μm, a strength of 0.4 – 9.7 MPa, and a Young’s modulus 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 a strength of 55 MPa and a Young’s modulus of 4.5 GPa. Preliminary data for the synthetic HA-PMMA composite showed a strength of 42 MPa and a modulus of 0.8 GPa.

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

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

Bisphosphonate (Bp) was adsorbed on the surface of crystalline calcium phosphates (CP); hydroxyapatite (HAp), octacalcium phosphate (OCP) and Dicalcium phosphate dehydrate (DCPD). The amount of Bp adsorbed was the largest for DCPD per unit surface area, while the amount was the largest for HAp per unit weight. The composites of Bp and amorphous calcium phosphate (ACP) were synthesized by titrating calcium acetate solution into phosphate buffer solution containing Bp. The amount of Bp doped in the composites was 366 μg / mg and was approximately 7 times larger than those of Bp adsorbed on the crystalline Calcium phosphates. TG-DTA measurements of a Bp-calcium and the composite indicated exothermic peaks due to Bp combustion, of which temperature were shifted to higher temperature for the composite. Bp in the composites was gradually released into phosphate buffered saline, while Bp was rapidly released into acetate buffer solution accompanied with the dissolution of ACP. This result suggests that the composite of Bp and ACP has potential for a drug-carrier releasing Bp in response to the condition of osteoclastic bone resorption.

The art and science of using biological tissue grafts from animal and human sources for various ailments is nascent. Various research groups around the world are actively investigating the potential prostheses of biological origin. Biological tissue grafts are rendered acellular through various methods of processing and fabrication before they are used for the specific purpose. The remainder is a scaffold that offers framework for host cellular repopulation and revascularization. Different methods of fixation have been explored over several decades to render the biological grafts suitable for use with or without extraction of cells. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize and deantigenize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Naturally derived biological scaffolds offer many mechanical, chemical and biological advantages over synthetic materials, and thus hold tremendous potential for use in tissue engineering therapies. Therefore the rationale of using biological grafts in usable forms is gaining importance in order to avoid unwanted chronic inflammatory reactions. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in various applications.

Poly(N-isopropylacrylamide) (PNIPAM), a classic thermo-sensitive polymer, has a lower critical solution temperature (LCST) at ∼32°C. In this work we have used molecular dynamics simulations to understand the origin of the LCST and agglomeration of PNIPAM chains of 5 and 30 monomer units (5-mer and 30-mer). Experimentally, when the concentration of PNIPAM is >1 ppm, polymer chains after undergoing coil-to-globule transition above the LCST aggregates to yield a stable colloidal dispersion.In our study two PNIPAM chains, consisting of 30 monomer units each, were placed in a cubic simulation cell and were subsequently solvated. Simulations were carried out below and above the LCST, namely at 278 and 310K for 10ns. Simulated trajectories were analyzed for structural and dynamical properties of both PNIPAM and water. We observe coil-to-globule transition in PNIPAM above the LCST. We also find that the PNIPAM chains agglomerate above the LCST. We also observe entanglement in PNIPAM chains below the LCST. We also study agglomeration of 5 PNIPAM chains each consisting of 5 monomer units. There was no significant difference in polymer agglomeration behavior across the LCST for these short chain oligomers. The agglomeration behavior is thus strongly correlated to the size of the polymer chains. These results provide fundamental insight into the atomistic scale mechanism of PNIPAM agglomeration across the LCST.