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Development of multifunctional films for peripheral nerve regeneration
Metin Uz1, Anup D Sharma2, Pratish Adhikari3
1Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, United States.
Acta Biomaterialia
|October 4, 2016
Summary
This study developed a PLLA film with NGF gradients and PA microparticles for peripheral nerve regeneration. The film enhances neurite outgrowth by co-delivering neurotrophic factors with controlled release.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Peripheral nerve injuries pose significant challenges to regeneration.
- Current strategies often lack controlled delivery of neurotrophic factors and topographical guidance.
- Developing advanced materials is crucial for improving nerve repair outcomes.
Purpose of the Study:
- To fabricate a poly(lactic acid) (PLLA) porous film with surface micropatterns for peripheral nerve regeneration.
- To incorporate nerve growth factor (NGF) gradients and polyanhydride (PA) microparticles for co-delivery of neurotrophic factors.
- To evaluate the film's potential in promoting neurite outgrowth and guiding nerve regeneration.
Main Methods:
- Fabrication of PLLA porous films using dry phase inversion with longitudinal micropatterns.
- Incorporation of NGF gradients on the film surface via ester-amine interactions.
- Loading of bioactive NGF into surface-eroding PA microparticles using spray drying.
- Co-delivery system utilizing PA microparticles within the film matrix for controlled release.
- Assessment of neurite outgrowth from PC12 cells on the fabricated films.
Main Results:
- Achieved high protein loading capacity (up to 80%) in PA microparticles and significant NGF surface loading (300 ng/cm²).
- Demonstrated tunable release kinetics of NGF with controlled diffusion coefficients and dissolution constants.
- Promoted guided neurite extension from PC12 cells, with up to 10μm total neurite length per cell in 2 days.
- The NGF surface gradient and longitudinal micropatterns facilitated directional neurite outgrowth.
Conclusions:
- The developed multifunctional PLLA film with NGF gradients and PA microparticles offers a promising strategy for peripheral nerve regeneration.
- This co-delivery system enhances neurite outgrowth and provides directional guidance.
- The platform allows for tunable delivery of multiple growth factors and has potential for in vivo applications as nerve conduits.

