HEMA Hydrogel Copolymer Surface Chemistry Influences Localization and Release of Single and Multiple Wound Healing Growth Factors

26 Pages Posted: 9 Apr 2019

See all articles by Shohini Sen-Britain

Shohini Sen-Britain

State University of New York at Buffalo - Department of Chemistry

Derek Britain

University of California, San Francisco (UCSF) - Cardiovascular Research Institute; University of California, San Francisco (UCSF) - Biophysics Graduate Program

Wesley L. Hicks Jr

Roswell Park Comprehensive Cancer Center - Department of Head and Neck/Plastic and Reconstructive Surgery

Joseph A. Gardella Jr

State University of New York at Buffalo - Department of Chemistry

Date Written: April 9, 2019

Abstract

(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

Suggested Citation

Sen-Britain, Shohini and Britain, Derek and Jr, Wesley L. Hicks and Jr, Joseph A. Gardella, HEMA Hydrogel Copolymer Surface Chemistry Influences Localization and Release of Single and Multiple Wound Healing Growth Factors (April 9, 2019). Available at SSRN: https://ssrn.com/abstract=3368801

Shohini Sen-Britain

State University of New York at Buffalo - Department of Chemistry

Amherst, NY 14260
United States

Derek Britain

University of California, San Francisco (UCSF) - Cardiovascular Research Institute

555 Mission Bay Boulevard South
San Francisco, CA 94158
United States

University of California, San Francisco (UCSF) - Biophysics Graduate Program

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Wesley L. Hicks Jr

Roswell Park Comprehensive Cancer Center - Department of Head and Neck/Plastic and Reconstructive Surgery

Elm & Carlton Streets
Buffalo, NY 14263
United States

Joseph A. Gardella Jr (Contact Author)

State University of New York at Buffalo - Department of Chemistry ( email )

Amherst, NY 14260
United States

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