The innervation of the rat external auditory meatus has contributions from several nerves. Fluoro-gold, a retrograde neuronal tracer, was used to determine the relative contributions from neurons in cranial and spinal ganglia, and to distinguish any difference in the sensory and motor innervation between the outer cartilaginous and inner bony portions. The following ganglia were examined: the trigeminal, geniculate, glossopharyngeal, vagal, superior cervical, and dorsal root (C2-C4) ganglia. All selected ganglia demonstrated innervation of the external ear canal, particularly the trigeminal, glossopharyngeal, facial, and vagal ganglia. The geniculate and glossopharyngeal ganglia contributed more innervation to the inner osseous portion than to the outer cartilaginous portion of the external ear canal, and the vagal ganglion contributed relatively equally.

Composite microparticles (MPs) with layered architecture, engineered from poly(L-lactic acid) (PLLA) and poly(D,L-lactic-co-glycolic acid) (PLGA), are promising devices for achieving the delayed release of proteins. Here, we build on a water-in-oil-in-oil-in-water emulsion method of fabricating layered MPs with an emphasis on modulating the delay period of the protein release profile. Particle hardening parameters (i.e. polymer precipitation rate and total hardening time) following water-in-oil-in-oil-in-water emulsions are known to affect MP structure such as the core/shell material and cargo localization. We demonstrate that layered MPs fabricated with two different solvent evaporation parameters not only alter polymer and protein distribution within the hardened MPs, but also affect their protein release profiles. Secondly, we hypothesize that ethanol (EtOH), a semi-polar solvent miscible in both the solvent (dichloromethane; DCM) and non-solvent aqueous phases, likely alters DCM and water flux from the dispersed oil phase. The results reveal that EtOH affects protein distribution within MPs, and may also influence MP structural properties such as porosity and polymer distribution. To our knowledge, we are the first to demonstrate EtOH as a means for modulating critical release parameters from protein-loaded, layered PLGA/PLLA MPs. Throughout all the groups in the study, we achieved differential delay periods (between 0 – 30 days after an initial burst release) and total protein release periods (~30 – >58 days) as a function of solvent evaporation parameters and EtOH content. The layered MPs proposed in the study potentially have wide-reaching applications in tissue engineering for delayed and sequential protein release.

Chemotaxis enables cellular communication and movement within the body. This review focuses on exploiting chemotaxis as a tool for repair of the central nervous system (CNS) damaged from injury and/or degenerative diseases. Chemokines and factors alone may initiate repair following CNS injury/disease, but exogenous administration may enhance repair and promote regeneration. This review will discuss critical chemotactic molecules and factors that may promote neural regeneration. Additionally, this review highlights how biomaterials can impact the presentation and delivery of chemokines and growth factors to alter the regenerative response.

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Stromal cell-derived factor-1 (SDF-1) and its key receptor CXCR4 have been implicated in directing cellular recruitment for several pathological/disease conditions thus also gained considerable attention for regenerative medicine. One regenerative approach includes sustained release of SDF-1 to stimulate prolonged stem cell recruitment. However, the impact of SDF-1 sustained release on the endogenous SDF-1/CXCR4 signaling axis is largely unknown as auto-regulatory mechanisms typically dictate cytokine/receptor signaling. We hypothesize that spatiotemporal presentation of exogenous SDF-1 is a key factor in achieving long-term manipulation of endogenous SDF-1/CXCR4 signaling. Here in the present study, we sought to probe our hypothesis using a transgenic mouse model to contrast the spatial activation of endogenous SDF-1 and CXCR4 in response to exogenous SDF-1 injected in bolus or controlled release (PLGA nanoparticles) form in the adult rodent cortex. Our data suggests that the manner of SDF-1 presentation significantly affected initial CXCR4 cellular activation/recruitment despite having similar protein payloads over the first 24 hrs (∼30ng for both bolus and sustained release groups). Yet, one week post-injection, this response was negligible. Therefore, the transient nature CXCR4 recruitment/activation in response to bolus or controlled release SDF-1 indicated that cytokine/receptor auto-regulatory mechanisms may demand more complex release profiles (i.e. delayed and/or pulsed release) to achieve sustained cellular response.