HEMA Hydrogel Copolymer Surface Chemistry Influences Localization and Release of Single and Multiple Wound Healing Growth Factors
26 Pages Posted: 9 Apr 2019
Date Written: April 9, 2019
(Hydroxyethyl)methacrylate (HEMA)-based hydrogel copolymers are ideal growth factor delivery vehicles for wound healing purposes. However, copolymer surfaces often exhibit micron-scale phase segregation that can influence the behavior of proteins, cells, and tissues in contact with the surface. In this work, we used time-of-flight secondary ion mass spectrometry (ToF-SIMS), total internal reflectance fluorescence (TIRF) microscopy, and confocal microscopy to evaluate the effects of HEMA, HEMA/5% methyl methacrylate (HEMA/MMA), and HEMA/5% methacrylic acid (HEMA/MAA) copolymer surface chemistry on protein localization, surface concentration, release profiles, and 3D distribution. We evaluated polymers releasing Keratinocyte Growth Factor (KGF), and polymers co-releasing KGF, Epidermal Growth Factor (EGF), and Platelet Derived Growth Factor-AA (PDGF-AA). First, we characterized differences in the identity, shape, and size of pores at the polymer surfaces. Then, we found that phase segregation at the HEMA/MMA and HEMA/MAA copolymer surfaces increased localization, surface concentration and release of KGF in comparison to HEMA homopolymers. We also observed higher concentrations of KGF distributed throughout the first few microns of the copolymers. In the case of tandem growth factor release, increased interactions between the HEMA/MMA and HEMA/MAA copolymer surfaces and KGF, EGF, and PDGF-AA induced colocalization of KGF and PDGF-AA, causing KGF delivery to impede PDGF-AA delivery. In contrast, the HEMA homopolymer kept each growth factor spatially segregated, showed the least amount of colocalization, and efficiently delivered all three growth factors. We expect the observed differences between polymers to induce differential biological response in future cell-based assays modeling wound healing.
Keywords: ToF-SIMS, hydrogel, KGF, PDGF-AA, EGF, surface chemistry, phase segregation, wound healing, multiple growth factor delivery, microscopy
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