Approaches to neural tissue engineering using scaffolds for drug delivery

Abstract

This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented.

Figure 1

Schematic of the gradient maker used to create NGF concentration gradients in p(HEMA) gels using chambers A and B separated by a conduit. With the center valve closed, a known concentration of NGF and prepolymer solution were added to chamber A while an NGF-free prepolymer solution was added to chamber B. The center valve was opened and the peristaltic pump and stir bar were activated. The volumes in both chambers were equally depleted and mixed, and the resulting solution was delivered into a mold and allowed to polymerize, resulting in a gradient of entrapped or immobilized NGF in p(HEMA). Reproduced from reference [94], Copyright (2006), Mary Ann Liebert.

Figure 2

Comparison of two different fabrication of nitrocellulose scaffolds for delivery of a-MSH. A) Schematic of the reservoir delivery method where a-MSH was allowed to bind the electrode followed by a coating of nitrocellulose. B) Schematic of the matrix delivery method where the a-MSH was premixed with the nitrocellulose before coating the electrode. C) Diagram showing the effect of fabrication method on the cumulative controlled release profile. The percent a-MSH loading for Reservoir produced by adding 100 ng, Reservoir produced by adding 400 ng, Matrix produced by adding 100 ng and Matrix produced by adding 400 ng. Data shown are the average ± S.E.M. (n = 3). Reproduced from reference [53], Copyright (2005), Elsevier.

Figure 3

Schematic diagram showing the components of the heparin-binding delivery system. The bi-domain peptide is cross-linked into the fibrin gel via the transglutaminase activity of Factor XIIIa; heparin can bind to the peptide by electrostatic interactions. NT-3 can bind to the bound heparin, creating a gel-bound, non-diffusible complex. NT-3 can exist in the diffusible state, alone, or in a complex with free heparin. Reproduced from reference [81], Copyright (2004), Elsevier.

Figure 4

A) Chemistry schematic of the NGF immobilization process using azido chemistry. PAA was conjugated to an azido compound (PAA-azido). This conjugate was cast twice on PPy, followed by casting of NGF. UV light exposure promoted the formation of covalent bonds via the azido groups, immobilizing NGF to PPy. Reproduced from reference [38], Copyright (2006), Wiley. B) Chemical schematic of thiolization of NGF and subsequent conjugation to the PEO-PPO-PEO linker. Reproduced from reference [109], Copyright (2005), Koninklijke Brill NV.

Figure 5

Schematic of chemical oxidation used to dope polypyrrole with NT-3. A) Synthesis of polypyrrole showing the incorporation of the dopant A⁻. (B) Release of the dopant A⁻ during redox cycling of the polypyrrole. Reproduced from reference [41], Copyright (2006), Elsevier.