Spatiotemporal Control over Molecular Delivery and Cellular Encapsulation from Electropolymerized Micro‐ and Nanopatterned Surfaces

Bioactive, patterned micro- and nanoscale surfaces that can be spatially engineered for three-dimensional ligand presentation and sustained release of signaling molecules represent a critical advance for the development of next-generation diagnostic and therapeutic devices. Lithography is ideally suited to patterning such surfaces due to its precise, easily scalable, high-throughput nature; however, to date polymers patterned by these techniques have not demonstrated the capacity for sustained release of bioactive agents. We demonstrate here a class of lithographically-defined, electropolymerized polymers with monodisperse micro- and nanopatterned features capable of sustained release of bioactive drugs and proteins. We show that precise control can be achieved over the loading capacity and release rates of encapsulated agents and illustrate this aspect using a fabricated surface releasing a model antigen (ovalbumin) and a cytokine (interleukin-2) for induction of a specific immune response. We further demonstrate the ability of this technique to enable three-dimensional control over cellular encapsulation. The efficacy of the described approach is buttressed by its simplicity, versatility, and reproducibility, rendering it ideally suited for biomaterials engineering.

[1]  K. Mossman,et al.  Altered TCR Signaling from Geometrically Repatterned Immunological Synapses , 2005, Science.

[2]  E. Hall,et al.  An electrochemically grown polymer as an immobilisation matrix for whole cells: Application in an amperometric dopamine Sensor , 1990 .

[3]  A. L. Lacey,et al.  Covalent binding of viologen to electrode surfaces coated with poly(acrylic acid) prepared by electropolymerization of acrylate ions , 1993 .

[4]  Stephanie E. A. Gratton,et al.  Imparting size, shape, and composition control of materials for nanomedicine. , 2006, Chemical Society reviews.

[5]  Jörg Lahann,et al.  REACTIVE POLYMER COATINGS FOR BIOMIMETIC SURFACE ENGINEERING , 2006 .

[6]  Gengfeng Zheng,et al.  Detection, Stimulation, and Inhibition of Neuronal Signals with High-Density Nanowire Transistor Arrays , 2006, Science.

[7]  G. Vogel,et al.  Renovating the Heart , 2004, Science.

[8]  Serge Cosnier,et al.  Synthesis and characterization of a biotin-alginate conjugate and its application in a biosensor construction. , 2004, Biomacromolecules.

[9]  M. Baggiolini,et al.  Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes , 1996, The Journal of experimental medicine.

[10]  Serge Cosnier,et al.  Biosensors based on electropolymerized films: new trends , 2003, Analytical and bioanalytical chemistry.

[11]  Mark J. Miller,et al.  Two-Photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph Node , 2002, Science.

[12]  Tarek R. Fadel,et al.  Enhanced cellular activation with single walled carbon nanotube bundles presenting antibody stimuli. , 2008, Nano letters.

[13]  S. Rosenberg,et al.  Adoptive cell transfer therapy. , 2007, Seminars in oncology.

[14]  W. Bailey,et al.  Synthesis of poly‐ϵ‐caprolactone via a free radical mechanism. Free radical ring‐opening polymerization of 2‐methylene‐1,3‐dioxepane , 1982 .

[15]  M. Reed,et al.  Electropolymerization on microelectrodes: functionalization technique for selective protein and DNA conjugation. , 2006, Analytical chemistry.

[16]  David J Mooney,et al.  Spatiotemporal control over growth factor signaling for therapeutic neovascularization. , 2007, Advanced drug delivery reviews.

[17]  Samir Mitragotri,et al.  Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[18]  S. Cosnier Biomolecule immobilization on electrode surfaces by entrapment or attachment to electrochemically polymerized films. A review. , 1999, Biosensors & bioelectronics.

[19]  C. Schmidt,et al.  Micropatterned Polypyrrole: A Combination of Electrical and Topographical Characteristics for the Stimulation of Cells , 2007, Advanced functional materials.

[20]  M. Madou Fundamentals of microfabrication : the science of miniaturization , 2002 .

[21]  Ji Guo,et al.  Nanofabricated particles for engineered drug therapies: a preliminary biodistribution study of PRINT nanoparticles. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Eun-Suk Kim,et al.  Material-based deployment enhances efficacy of endothelial progenitor cells , 2008, Proceedings of the National Academy of Sciences.

[23]  M. Mrksich What can surface chemistry do for cell biology? , 2002, Current opinion in chemical biology.

[24]  Ze Zhang,et al.  Tissue reaction to polypyrrole-coated polyester fabrics: an in vivo study in rats. , 2002, Tissue engineering.

[25]  J. Pober,et al.  Engineering of multifunctional gels integrating highly efficient growth factor delivery with endothelial cell transplantation , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  Ali Khademhosseini,et al.  Stop-flow lithography to generate cell-laden microgel particles. , 2008, Lab on a chip.

[27]  S. Cosnier,et al.  Electrogeneration of a Hydrophilic Cross‐Linked Polypyrrole Film for Enzyme Electrode Fabrication. Application to the Amperometric Detection of Glucose , 2001 .

[28]  Li Shi,et al.  Nanoimprint lithography based fabrication of shape-specific, enzymatically-triggered smart nanoparticles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Joseph M DeSimone,et al.  Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. , 2005, Journal of the American Chemical Society.

[30]  G. Morgan,et al.  High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. , 2003, The New England journal of medicine.

[31]  T. Fahmy,et al.  A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[32]  Nicholas Ferrell,et al.  Fabrication of polymeric microparticles for drug delivery by soft lithography. , 2006, Biomaterials.

[33]  Erodible conducting polymers for potential biomedical applications. , 2002 .

[34]  A. Chilkoti,et al.  Structural optimization of a "smart" doxorubicin-polypeptide conjugate for thermally targeted delivery to solid tumors. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[35]  Paul M. George,et al.  Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics. , 2005, Biomaterials.