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 factorprimed 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.neurotransmitter ͉ regenerative medicine B iomaterials are widely used in disease treatment and improving human well-being (1, 2). Recently, significant advances have been made to impart biological activity to biomaterials. Most of the existing bioactive materials are derived from extracellular matrix or are modified with extracellular matrix motifs (3-8). The most widely used extracellular matrix motifs include protein epitopes such as Arg-Gly-Asp (4, 5, 9), Tyr-IleGly-Ser-Arg (10, 11), and Ile-Lys-Val-Ala-Val (6, 11) and glycosaminoglycans such as heparin (12,13). In addition to cellextracellular matrix interactions, cell differentiation and survival also depend on constant interactions with other cells through a plethora of messenger molecules (14-16). The biomaterial reported here is designed to use a chemical messenger to impart bioactivities to the resultant biodegradable polymers.We chose to focus on using bioactive materials for functional restoration of damaged nerves because it is a major challenge in medicine (17). An important class of chemical messengers in the nervous system is the neurotransmitters (18, 19). They are essential to neuronal outgrowth during embryonic and neonatal development and after injury (20-23). The depletion of neurotransmitters during embryonic development results in developmental defects of the brain, suggesting that neurotransmitters play crucial roles as morphogens or neurotrophic factors (24). Dopamine in particular is vital in axon growth and synapse formation during the embryonic stage (25). We postulated that a biocompatible material containing dopamine functiona...