This document discusses the development of biomimetic materials through the continuous processing and surface modification of polycaprolactone (PCL) nanofibers. Specifically:
1) The goal is to introduce multiple orthogonal chemical modifications onto nanofibers to produce a surface capable of attaching various bioactive cues like peptides.
2) A coextrusion and photochemical modification procedure is used to introduce and spatially control functional groups on the fibers.
3) Initial results show the substrate with dual RGD and OGP peptide modifications is sufficient to induce bone cell differentiation and adhesion, demonstrating the potential of these biomimetic materials.
1. Extracellular matrix (ECM) inspired biomimetic materials
The extra cellular matrix is a complex environment that
provides chemical and physical support cells. A key component
of biologically functional scaffolds is the need to introduce
chemical or biochemical cues that allow for cellular adhesion
proliferation, and differentiation, In biological systems, multiple
cues are needed to direct cell biology.
Continuous Processing of PCLNanofibers through Extrusion
Multifunctional and spatially controlled
bioconjugation to melt coextruded
nanofibers
Abigail A. Advincula1, Si-Eun Kim1, Emily C. Harker1, Jon Pokorski1*
1Department of Macromolecular Science & Engineering, Case Western Reserve University
2100 Adelbert Road, Cleveland, Ohio,d 44106
jon.pokorski@case.edu
Our goal for this project is to introduce multiple orthogonal
chemical modifications onto nanofibers in order to produce a
surface capable of attaching various bioactive cues.
We have recently reported a new class of fibrous
biomaterials using coextrusion and a photochemical
modification procedure to introduce functional groups onto the
fibers.
This project extends our methodology to control surface
modification density, describe methods to synthesize
multifunctional fibers, and provide methods to spatially control
functional group modification.
We investigate the effect of fiber modification with multiple
cell-responsive peptides, the RGD sequence and osteogenic
growth peptide (OGP), on substrates for osteoblast
differentiation.
Goal
Results
Introduction
Acknowledgements
The bioavailability of multiple peptides by our substrate
was sufficient to induce both bone differentiation and
cellular adhesion.
Utilizing multiple ‘click’ types of chemistry allows for the
covalent attachment of several different types of
molecules. This is a useful strategy if the CuAAC
reaction is not appropriate or if orthogonal chemistry may
be needed.
We report a simple method for surface modification that
enables the manipulation of surface concentration based
on UV fluence.
We have demonstrated control over modulus, fiber
alignment, and the deposition of multiple chemical
functionalities in a spatially controlled manner.
Results
Experimental
Conclusions
Synthetic scheme for multiple functional fiber variants
Oxime coupling of doxorubicin
Coextruded SEM images of coextruded PCL fibers
• Produce 1,024 (256×4) layer system with PEO surface layer
No organic solvent
Aligned fibers
Scalable
High Surface Area
(A) Digital images of fibers functionalized with AF488
under varying UV irradiation times. (B) UV-Vis spectra
of AF488 functionalized fibers following dissolution.
Dual gradient modification results Fiber modification with AF488
(A) Bifunctional gradient modification scheme. (B)
Fluorescent images of PCL bundles. Top: red channel to
visualize TAMARA, Middle: green channel to visualize
AF488, Bottom: overlaid green and red channels.
(A) Schematic for reversible oxime coupling of DOX. (B) ATR
FT-IR spectra of PCL (black) and PCL-Alkoxyamine (red). (C)
Doxorubicin kinetic release profile, measured using UV-Vis
absorbance at 490 nm in pH 4.5 MES buffer in increments of 10
minutes.
Relative ALP activity for peptide modified substrates
XPS spectra of peptide modified fiber scaffolds
Dual indicates modification with both OGP and RGD.
I would like to thank Professor Jonathan Pokorski for his
guidance on this project. I would also like to thank Si-Eun
Kim and Emily Harker for their help with sample
preparation and characterization.
Scanning electron micrograph of aligned fibers
following PEO dissolution. Scale bar – 10 μm.