A neuroinductive biomaterial based on dopamine

Chemical messengers such as neurotransmitters play an important role in cell communication, differentiation, and survival. We have designed and synthesized a bioactive biomaterial that derived its biological activity from dopamine. The resultant biodegradable polymer, PCD, has pendent groups bearing dopamine functionalities. Image analysis demonstrated that nerve growth factor-primed rat pheochromocytoma cells (PC12) and explanted rat dorsal root ganglions attached well and displayed substantial neurite outgrowth on the polymer surface. Furthermore, PCD promoted more vigorous neurite outgrowth in PC12 cells than tissue culture polystyrene, laminin, and poly(d-lysine). The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls. A subset of PC12 cells displayed high filopodium density on PCD. The addition of dopamine in culture medium had little effect on the differentiation of PC12 cells on tissue culture polystyrene. Tyrosine, the precursor of dopamine, did not exhibit this ability to impart specific bioactivity to an analogous polymer. Thus, the dopamine functional group is likely the origin of the inductive effect. PCD did not cause nerve degeneration or fibrous encapsulation when implanted immediately adjacent to the rat sciatic nerves. This work is a step toward creating a diverse family of bioactive materials using small chemical messengers as monomers.

[1]  N. Grigoriadis,et al.  Recovery, innervation profile, and contractile properties of reinnervating fast muscles following postnatal nerve crush and administration of L-Dopa. , 2004, Brain research. Developmental brain research.

[2]  H. Prentice,et al.  Immunocytochemical detection of breast cancer cells: a comparison of three attachment factors. , 1997, Journal of hematotherapy.

[3]  B. Guptaroy,et al.  Repeated amphetamine treatment induces neurite outgrowth and enhanced amphetamine‐stimulated dopamine release in rat pheochromocytoma cells (PC12 cells) via a protein kinase C‐ and mitogen activated protein kinase‐dependent mechanism , 2003, Journal of neurochemistry.

[4]  R Langer,et al.  Stimulation of neurite outgrowth using an electrically conducting polymer. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Baokang Jin,et al.  In-situ FTIR Spectroelectrochemical Study of Dopamine at a Glassy Carbon Electrode in a Neutral Solution , 2002, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[6]  M. Gnegy,et al.  Repeated, intermittent treatment with amphetamine induces neurite outgrowth in rat pheochromocytoma cells (PC12 cells) , 2002, Brain Research.

[7]  K. Vrana,et al.  Cytotoxic and genotoxic potential of dopamine , 1999, Journal of neuroscience research.

[8]  Ronald T Raines,et al.  Self-assembly of synthetic collagen triple helices. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Hubbell,et al.  Development of fibrin derivatives for controlled release of heparin-binding growth factors. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[10]  P. Marchisio,et al.  Acetylcholine system and neural development. , 1971, Neurosciences research.

[11]  Jeffrey A. Hubbell,et al.  Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension , 2000, Nature Biotechnology.

[12]  Bruce P. Lee,et al.  Mussel adhesive protein mimetic polymers for the preparation of nonfouling surfaces. , 2003, Journal of the American Chemical Society.

[13]  D. Zachor,et al.  Cocaine inhibits NGF-induced PC12 cells differentiation through D1-type dopamine receptors , 2000, Brain Research.

[14]  F. Si,et al.  Glutathione protects PC12 cells from ascorbate- and dopamine-induced apoptosis , 1998, Experimental Brain Research.

[15]  S. Im,et al.  A Novel Polymeric Ionomer as a Potential Biomaterial: Crystallization Behavior, Degradation, and In‐Vitro Cellular Interactions , 2005 .

[16]  Y. Kato,et al.  Effects of dopamine and L‐DOPA on survival of PC12 cells , 2000, Journal of neuroscience research.

[17]  Robert Langer,et al.  Advances in Biomaterials, Drug Delivery, and Bionanotechnology , 2003 .

[18]  M. Mattson.  Neurotransmitters in the regulation of neuronal cytoarchitecture , 1988, Brain Research Reviews.

[19]  T. Weissman,et al.  Identification of diverse nerve growth factor-regulated genes by serial analysis of gene expression (SAGE) profiling. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. van Kesteren,et al.  The Role of Neurotransmitters in Neurite Outgrowth and Synapse Formation , 2003, Reviews in the neurosciences.

[21]  T. Hökfelt,et al.  Messenger plasticity in primary sensory neurons following axotomy and its functional implications , 1994, Trends in Neurosciences.

[22]  G. Meredith,et al.  Effects of dopamine depletion on the morphology of medium spiny neurons in the shell and core of the rat nucleus accumbens , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  Krista L. Niece,et al.  Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers , 2004, Science.

[24]  G. Evans,et al.  Challenges to nerve regeneration. , 2000, Seminars in surgical oncology.

[25]  A. Sanghvi,et al.  Biomaterials functionalization using a novel peptide that selectively binds to a conducting polymer , 2005, Nature materials.

[26]  R. Langer,et al.  A tough biodegradable elastomer , 2002, Nature Biotechnology.

[27]  Christine E Schmidt,et al.  Neural tissue engineering: strategies for repair and regeneration. , 2003, Annual review of biomedical engineering.

[28]  R. Langer,et al.  Designing materials for biology and medicine , 2004, Nature.

[29]  C. Stevens.  Neurotransmitter Release at Central Synapses , 2003, Neuron.

[30]  A. Ewing,et al.  Differentiated PC12 Cells , 2002 .

[31]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[32]  C. Thompson,et al.  Apoptosis in the pathogenesis and treatment of disease , 1995, Science.

[33]  J. P. Long,et al.  Preparation and biological actions of some symmetrically N,N-disubstituted dopamines. , 1978, Journal of medicinal chemistry.

[34]  P. Aebischer,et al.  Neuronal cell attachment to fluorinated ethylene propylene films with covalently immobilized laminin oligopeptides YIGSR and IKVAV. II. , 1995, Journal of biomedical materials research.

[35]  Kristi L Kiick,et al.  Functionalizing electrospun fibers with biologically relevant macromolecules. , 2005, Biomacromolecules.

[36]  R. Zigmond,et al.  Regulation of Neuropeptide Expression in Sympathetic Neurons , 1997, Annals of the New York Academy of Sciences.

[37]  M. Iwaki,et al.  Neuronal attachment and outgrowth on a micropatterned fluorinated polyimide surface , 2004, Journal of Artificial Organs.

[38]  M. Hanson,et al.  Depolarization and cAMP Elevation Rapidly Recruit TrkB to the Plasma Membrane of CNS Neurons , 1998, Neuron.

[39]  S. Snyder.  Turning off Neurotransmitters , 2006, Cell.

[40]  Ying Luo,et al.  A photolabile hydrogel for guided three-dimensional cell growth and migration , 2004, Nature materials.

[41]  Antonios G Mikos,et al.  In vitro degradation of porous poly(propylene fumarate)/poly(DL-lactic-co-glycolic acid) composite scaffolds. , 2005, Biomaterials.

[42]  Eben Alsberg,et al.  Engineering growing tissues , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Philip R. Kuhl,et al.  Tethered epidermal growth factor as a paradigm for growth factor–induced stimulation from the solid phase , 1996, Nature Medicine.

[44]  D. Baltimore,et al.  Interleukin 3-dependent survival by the Akt protein kinase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.