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We report the development of a photoreversible cell culture substrate. We demonstrate the capacity to modify the adhesivity of the substrate using light, altering its capacity to support cell growth. Polyelectrolyte multilayers (PEMs) were used to produce tunable substrates of different thickness and matrix stiffness, which have different intrinsic capacities to support cell adhesion and survival. Surfaces were top-coated with a poly(acrylic acid)-poly(allylamine hydrochloride) polyelectrolyte bilayer functionalized with a small fraction (<1%) of an azobenzene-based photoswitchable sidegroup, which included the cell-adhesive three-amino-acid peptide RGD. Irradiation with light-induced geometric switching of the azo bond, resulting in changes to RGD exposure and consequently to cell adhesion and survival, was investigated on a variety of surfaces of different thickness and stiffness. Substrate stiffness, as modified by the thickness, had a significant influence on the adhesion of NIH 3T3 cells, consistent with previous studies. However, by disrupting the isomerization state of the azobenzene-linked RGD and exposing it to the surface, cell adhesion and survival could be enhanced up to 40% when the positioning of the RGD peptide was manipulated on the softest substrates. These findings identify permissive, yet less-than-optimal, cell culture substrate conditions that can be substantially enhanced using noninvasive modification of the substrate triggered by light. Indeed, where cell adhesion was tuned to be suboptimal under baseline conditions, the light-induced triggers displayed the most enhanced effect, and identification of this 'Goldilocks zone' was key to enabling light triggering.

We present a method of tuning surface chemistry and nerve cell behavior by photo-cross-linking methoxy poly(ethylene glycol) monoacrylate (mPEGA) with hydrophobic, semicrystalline poly(ε-caprolactone) diacrylate (PCLDA) at various weight compositions of mPEGA (ø(m)) from 2 to 30%. Improved surface wettability is achieved with corresponding decreases in friction, water contact angle, and capability of adsorbing proteins from cell culture media because of repulsive PEG chains tethered in the network. The responses of rat Schwann cell precursor line (SpL201), rat pheochromocytoma (PC12), and E14 mouse neural progenitor cells (NPCs) to the modified surfaces are evaluated. Nonmonotonic or parabolic dependence of cell attachment, spreading, proliferation, and differentiation on ø(m) is identified for these cell types with maximal values at ø(m) of 5-7%. In addition, NPCs demonstrate enhanced neuronal differentiated lineages on the mPEGA/PCLDA network at ø(m) of 5% with intermediate wettability and surface energy. This approach lays the foundation for fabricating heterogeneous nerve conduits with a compositional gradient along the wall thickness, which are able to promote nerve cell functions within the conduit while inhibiting cell attachment on the outer wall to prevent potential fibrous tissue formation following implantation.

Zwitterionic sulfobetaine methacrylate (SBMA) polymers were known to possess excellent antifouling properties due to high hydration capacity and neutral charge surface. In this study, copolymers of SBMA and acrylic acid (AA) with a variety of compositions were synthesized and were immobilized onto polymeric substrates with layer-by-layer polyelectrolyte films via electrostatic interaction. The amounts of platelet adhesion and fibrinogen adsorption were determined to evaluate hemocompatibility of poly(SBMA-co-AA)-modified substrates. Among various deposition conditions by modulating SBMA ratio in the copolymers and pH of the deposition solution, poly(SBMA(56)-co-AA(44)) deposited at pH 3.0 possessed the best hemocompatibility. This work demonstrated that poly(SBMA-co-AA) copolymers adsorbed on polyelectrolyte-base films via electrostatic interaction improve hemocompatibility effectively and are applicable for various substrates including TCPS, PU, and PDMS. Furthermore, poly(SBMA-co-AA)-coated substrate possesses great durability under rigorous conditions. The preliminary hemocompatibility tests regarding platelet adhesion, fibrinogen adsorption, and plasma coagulation suggest the potential of this technique for the application to blood-contacting biomedical devices.

Polymer brushes show great promise in next-generation antibiofouling surfaces. Here, we have studied the influence of polymer brush architecture on protein resistance. By carefully optimizing reaction conditions, we were able to polymerize oligoglycerol-based brushes with sterically demanding linear or dendronized side chains on gold surfaces. Protein adsorption from serum and plasma was analyzed by surface plasmon resonance. Our findings reveal a pronounced dependence of biofouling on brush architecture. Bulky yet flexible side chains as in dendronized brushes provide an ideal environment to repel protein-possibly through formation of a hydration layer, which can be further enhanced by presenting free hydroxyl groups on the polymer brushes. A deeper understanding of how brush architecture influences protein resistance will ultimately enable fabrication of surface coatings tailored to specific requirements in biomedical applications.

Immobilizing poly(butyl acrylate) (PBA) on cellulose microfibrils (CMFs) by atom transfer radical polymerization (ATRP) of butyl acrylate (BA) on the surface of 2-bromoisobutyryl-functionalized CMF generated highly hydrophobic microfibrils (CMF-PBA) with a hard core and a soft-shell structure. TGA and static water contact angle results suggested that the surfaces of the modified CMF samples were not completely covered by PBA chains until the molecular weight of grafts became sufficiently long. The GPC results indicated that the grafts with low molecular weight showed controlled/"living" characteristics of the surface-initiated ATRP; however, there existed more side reactions with the increase in molecular weights. Biocomposites consisting of polypropylene (PP) and CMF-PBA samples exhibited significantly improved compatibility, interface adhesion, and mechanical properties with the increase in PBA graft length. The findings confirmed that the longer grafts facilitated the better entanglement of PBA grafts with PP macromolecules and thus further improved the mechanical properties.

There has been little study on the effect of composition or molecular weight on the biodegradation rate of photo-cross-linked biodegradable aliphatic polyesters though such information is important for tissue engineering scaffolds. We have synthesized a new series of photopolymerizable linear poly(epsilon-caprolactone-co-lactide-co-glycolide) diacrylates with different molecular weights (Mn = 1800, 4800, and 9300 Da) and compositions (20%, 40%, and 60% epsilon-CL) and studied their biodegradation rates. The resultant oligomers were amorphous and appeared as viscous liquids at room temperature. Liquid-to-solid polymerization was carried out by UV irradiation in the presence of a photoinitiator. The photocuring yield was high (greater than 95%), and the photo-cross-linked polymers were amorphous and rubbery. Mechanical measurements showed that the polymers can be stretchable or rigid; the high molecular weight/low epsilon-CL network has a strain of 176% and a modulus of 1.66 MPa while the low molecular weight/high epsilon-CL network has a strain of 21% and a modulus of 12.3 MPa. In a 10 week in vitro biodegradation study, the polymers exhibited a two-stage degradation behavior. In the first stage, the polymer weight and strain remained almost constant, but a linear decrease in the Young's modulus (E) and ultimate stress (sigma) were observed. Lower oligomer molecular weight or epsilon-CL content correlated with a faster decrease in Young's modulus. In the second stage, which began when the Young's modulus dropped below 1 MPa, there was rapid weight loss and strain increase. The lower the epsilon-CL content, the earlier the second stage happened. Low molecular weight and high epsilon-CL content correlated with a longer modulus half-life (time for the modulus to degrade to 50% of its initial value). The degradation results suggest principles that may be helpful in predicting the biodegradation behavior of similar polymeric cross-linked networks. Films formed from these new polymers have excellent biocompatibility with smooth muscle cells.

The approach of employing N-glycinylmaleamic acid (NGMA) as an efficient cosurfactant to provide microemulsion polymerization of butyl acrylate using a weight ratio of sodium dodecyl sulfate (SDS)/butyl acrylate (BA) at

Blends of cross-linked poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(d,l-lactide) (PLA) were prepared by mixing photoactive PEGDMA (molecular mass: 875 g/mol) and PLA, and subsequently photopolymerizing the mixture with visible light. The effects of PLA molecular mass and mass fraction on the rheological properties of the PEGDMA/PLA mixtures, and on the degree of methacrylate vinyl conversion (DC), as well as blend miscibility, microstructure, mechanical properties, in vitro swelling behavior, and cell responses were studied. PLA-2K (molecular mass: 2096 g/mol) and PLA-63K (molecular mass: 63 000 g/mol) formed miscible and partially miscible blends with cross-linked PEGDMA, respectively. The addition of the PLA-2K did not affect the immediate or post-cure (>24 h) DC of the PEGDMA upon photopolymerization. However, the addition of PLA-63K decreased the immediate DC of the PEGDMA, which can be increased through extending the curing time or post-curing period. Compared to the cross-linked neat PEGDMA and PLA-2K/PEGDMA blends, PLA-63K/PEGDMA blends were significantly stronger, stiffer, and tougher. Both types of blends and the cross-linked PEGDMA swelled when soaked in a phosphate buffered saline (PBS) solution. The attachment and spreading of MCT3-E1 cells increased with increasing PLA-63K content in the blends. The facile and rapid formation of PEGDMA/PLA blends by photopolymerization represents a simple and efficient approach to a class of biomaterials with a broad spectrum of properties.

Peroxidation, epoxidation, and/or perepoxidation reactions of soybean oil under air at room temperature resulted in cross-linked polymeric soybean oil peroxides on the surface along with the waxy soluble part, sPSB, with a molecular weight of 4690, containing up to 2.3 wt % peroxide. This soluble polymeric oil peroxide, sPSB, initiated the free radical polymerization of either methyl methacrylate (MMA) or n-butyl methacrylate (nBMA) to give PSB-g-PMMA and PSB-g-PnBMA graft copolymers. The polymers obtained were characterized by (1)H NMR, thermogravimetric analysis, differential scanning calorimetry, and gel permeation chromatography techniques. Polymeric oil as a plasticizer lowered the glass transition of the PSB-g-PMMA graft copolymers. PSB-g-PMMA and PSB-g-PnBMA graft copolymer film samples were also used in cell culture studies. Fibroblast and macrophage cells were strongly adhered and spread on the copolymer film surfaces, which is important in tissue engineering. Bacterial adhesion on PSB-g-PMMA graft copolymer was also studied. Both Staphylococcus epidermidis and Escherichia coli adhered on the graft copolymer better than on homo-PMMA. Furthermore, the latter adhered much better than the former.

Well-defined (nearly monodispersed) poly(poly(ethylene glycol)monomethacrylate)-Si hybrids were prepared via surface-initiated atom transfer radical polymerization (ATRP) of the poly(ethylene glycol)monomethacrylate (PEGMA) macromonomer on the hydrogen-terminated Si(111) surface (Si-H surface). Both the active chloride groups at the chain ends (from the ATRP process) and the chloride groups converted from some ( approximately 32%) of the -OH groups of the Si-C bonded PEGMA polymer, or P(PEGMA), brushes were used as leaving groups for the covalent coupling of heparin. For the heparinized P(PEGMA)-Si hybrid surfaces, protein adsorption and platelet adhesion were significantly suppressed. The well-defined and dense P(PEGMA) brushes, prepared from surface-initiated ATRP, had allowed the immobilization of a relatively high concentration of heparin (about 14 mug/cm(2)). The resulting silicon surface exhibited significantly improved antithrombogenecity with a plasma recalcification time (PRT) of about 150 min. The persistence of high bioactivity for the immobilized heparin on the hybrid surfaces can be attributed to the biocompatibility of the PEGMA units, as well as their role as spacers in providing the immobilized heparin with a higher degree of conformational freedom in a more hydrophilic environment. Thus, the heparin-coupled P(PEGMA)-Si hybrids with anti-fouling and antithrombogenic surfaces are potentially useful in silicon-based implantable devices and tissue engineering.

Hydrogels composed of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) were prepared by redox polymerization with peptide cross-linkers to create an artificial extracellular matrix (ECM) amenable for testing hypotheses regarding cell proliferation and migration in three dimensions. Peptide degradable cross-linkers were synthesized by the acrylation of the amine groups of glutamine and lysine residues within peptide sequences potentially cleavable by matrix metalloproteinases synthesized by mammalian cells (e.g., osteoblasts). With the peptide cross-linker, loosely cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their phase transition behavior, lower critical solution temperature (LCST), water content, and enzymatic degradation properties were investigated. The peptide-cross-linked P(NIPAAm-co-AAc) hydrogels were pliable and fluidlike at room temperature and could be injected through a small-diameter aperture. The LCST of peptide-cross-linked hydrogel was influenced by the monomer ratio of NIPAAm/AAc but not by cross-linking density within the polymer network. A peptide-cross-linked hydrogel with a 97/3 molar ratio of NIPAAm/AAc exhibited a LCST of approximately 34.5 degrees C. Swelling was influenced by NIPAAm/AAc monomer ratio, cross-linking density, and swelling media; however, all hydrogels maintained more than 90% water even at 37 degrees C. In enzymatic degradation studies, breakdown of the peptide-cross-linked P(NIPAAm-co-AAc) hydrogels was dependent on both the concentration of collagenase and the cross-linking density. These results suggest that peptide-cross-linked P(NIPAAm-co-AAc) hydrogels can be tailored to create environmentally-responsive artificial extracellular matrixes that are degraded by proteases.

An amphiphilic hydrogel network was synthesized from a cross-linked poly(2-hydroxyethyl methacrylate) backbone copolymerized with the monomers 3-(trimethoxysilyl)propyl methacrylate (PMA) and dimethylaminoethyl methacrylate (DMAEMA) using tetraethylene glycol diacrylate (TEGDA) as cross-linker and using the radical initiator system comprising N,N,N',N'-tetramethylethylenediamine and ammonium peroxydisulfate. The degree of hydration of hydrogel slabs was investigated as functions of varying monomer compositions and cross-link density and as a function of pH and ionic strength of the bathing medium. As much as a 45% increase in hydration was observed for hydrogels containing 15 mol % DMAEMA upon reducing the pH of the bathing medium from 8.0 to 2.0. This confirms the pH-modulated swelling of amine-containing hydrogels. Increasing the concentration of TEGDA cross-linker from 3 to 12 mol % in a 10 mol % DMAEMA-containing hydrogel resulted in only a 10% reduction in the degree of hydration of the gel. There was, however, a 40-50% reduction in the degree of hydration of a 15 mol % DMAEMA hydrogel upon increasing the molar composition of PMA from 0 up to 20 mol %. The presence of PMA confers hydrophobic character that reduces hydration and introduces additional cross-links that reduce network mesh size. The water content of the hydrogel was consistently higher in buffers of lower ionic strength. The reversible pH-dependent swelling observed in these studies, along with the control of cross-link density afforded by the PMA component, endows these biocompatible materials with potential for use in pH-controlled drug delivery of more hydrophobic drugs and present new compositions for in vitro and in vivo biocompatibility studies.