1. Drug Delivery to Nerve Cell from a Biomaterial

2. Biomaterial matrices for drug release can be applied to in-vivo tissue regeneration This example shows modeling of a nerve regeneration guide, illustrating the use of COMSOL Multiphysics in bio-engineering applications The model involves detailed drug release kinetics and species transport Factors governing the drug release rate can readily be screened by simulations: –the drug/biomaterial binding affinity –biomaterial degradation –drug loading –the geometry and composition of the biomaterial matrix Introduction

3. Model Definition – Geometry Damaged nerve ends are joined in a regeneration guide, composed by a biomaterial matrix loaded with a drug A 2D axial symmetric model describes the system matrix nerve cells surrounding medium 11 22 33 nerve biomaterial matrix

4. Model Definition – Chemistry Drug Release by Dissociation: –In the absence of enzyme (E) the drug (d) is released by simple dissociation from the binding peptide (p or mp) Drug Release by Matrix degradation: –In the presence of enzyme, binding peptides are cleaved from the matrix sites, increasing total drug release –The enzyme is associated with the cell tissue to be regenerated drug dissociation matrix degradation

5. Model Definition – Equations Mass Balances: –Rate expressions (matrix domain) –Michaelis-Menten kinetics

6. Results The presence of matrix degrading enzyme in the nerve cell tissue leads to enhanced drug delivery in the damaged cell region.

7. Results The full reaction/transport description allows for ready evaluation of factors influencing the rate of drug delivery, e.g: –Matrix degradation with respect to geometry and time –Effect of drug loading (ratio of occupied to unoccupied matrix sites, mpd:mp)

8. A guide delivers a regenerating drug to damaged nerve ends. The model involves detailed drug release kinetics of drug dissociation/association reactions as well as matrix degradation through enzyme catalysis described by Michaelis-Menten kinetics. Biomaterial Matrix Surrounding Medium Nerve Cells Drug Delivery