**11. Biomaterial-based drug delivery systems**

While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels, and combinations of these systems.

Drug delivery systems transport biological active agents, such as growth factors and genetic material, into the desired location to promote beneficial effects for the treatment of diseases and disorders [52], osmotic pumps for the delivery of neurotrophic factors [53] to target site, affinity-based delivery systems (ABDS) in which drug loading and controlled release are achieved through the interactions of therapeutic drug and the delivery system, and reservoir-based delivery systems, where a polymer structure encapsulates the drug while its release is controlled via the material properties.

## **12. Affinity-based delivery systems (ABDS)**

ABDS operate through the noncovalent interactions between device material and target drug [54] in a similar pattern to the interactions that occur in the extracellular matrix where the delivery of proteins and other biomolecules are controlled [55]. ABDS include molecular imprinting, cyclodextrin-based delivery, and heparin-based delivery [56]. Molecular imprinting uses polymer networks synthesized via a precursor molecule that is removed to reveal an imprint that acts as an affinity binding zone. In cyclodextrin-based delivery systems, small hydrophobic drugs are attracted to the hydrophobic center of an oligosaccharide cyclodextrin torus, which permits the complexes formation with enhanced solubility when compared to the drug itself. ABDS is observed to be superior to traditional reservoir-based systems as the release characteristics are dependent on the activities occurring between the drug and the matrix in a way not affected by the matrix properties [57].

#### **13. Reservoir-based delivery systems (RBDS)**

Reservoir-based delivery systems (RBDS) are porous with drug release rate controlled by diffusion [58]. In RBDS, the drug is immersed or dissolved in a polymer solvent/reservoir. The drug penetrates via the biodegradable polymer structure to control the initial release followed by another release as surface and bulk erosion

occurs in polymer reservoir. RBDS include nanogels, nanoparticles, micelles, hydrogels, microspheres, and electrospun nanofibers.
