(616a) Amphiphilic Polyanhydride Films Promote Stem Cell Differentiation and Proliferation

Several challenges currently exist in the design and development of tissue engineering constructs for neural regeneration. These challenges often require that the materials provide a non-toxic, non-immunogenic interface that promotes cellular adhesion and has the ability to control the release of cell regulating molecules or factors. Polyanhydrides are a class of biocompatible polymers which have previously demonstrated the ability to control protein release kinetics and stability, modulate the immune response, as well as influence cellular adhesion. Specifically, amphiphilic polyanhydrid copolymers composed of 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and 1,6-bis(p-carboxyphenoxy) hexane (CPH) are capable of promoting human neural stem cell adhesion and differentiation toward glial and neuronal phenotypes. Additionally, they do not enhance inflammatory or immune signaling responses from immune cells, further emphasizing their potential in tissue engineering.

In this work, we have evaluated the ability of CPTEG:CPH polymer films to provide a controlled delivery platform for brain-derived neurotrophic factor (BNDF) and interleukin-6 (IL-6) and their effects on normal human neural progenitor cell (hNPC) differentiation and proliferation. 50:50 CPTEG:CPH polymer films were able to deliver functional BDNF and IL-6 to the hNPCs, promoting equivalent or higher levels of proliferation and neuronal differentiation than the equivalent  doses delivered soluble over a three dose regimen. Furthermore, hNPCs incubated on 50:50 CPTEG:CPH polymer films encapsulating IL-6 demonstrated a significant increase in neuronal proliferation over all other treatment groups. These findings demonstrate the capacity of amphiphilic polymer films to be used as controlled delivery tissue engineering platforms for neuronal regeneration.