Interplay of anionic charge, poly(ethylene glycol), and iodinated tyrosine incorporation within tyrosine-derived polycarbonates: Effects on vascular smooth muscle cell adhesion, proliferation, and motility

Patrick A. Johnson, Arnold Luk, Aleksey Demtchouk, Hiral Patel, Hak Joon Sung, Matthew D. Treiser, Simon Gordonov, Larisa Sheihet, Das Bolikal, Joachim Kohn, Prabhas V. Moghe

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Regulation of smooth muscle cell adhesion, proliferation, and motility on biomaterials is critical to the performance of blood-contacting implants and vascular tissue engineering scaffolds. The goal of this study was to examine the underlying substrate-smooth muscle cell response relations, using a selection of polymers representative of an expansive library of multifunctional, tyrosine-derived polycarbonates. Three chemical components within the polymer structure were selectively varied through copolymerization: (1) the content of iodinated tyrosine to achieve X-ray visibility; (2) the content of poly(ethylene glycol) (PEG) to decrease protein adsorption and cell adhesivity; and (3) the content of desaminotyrosyl-tyrosine (DT), which regulates the rate of polymer degradation. Using quartz crystal microbalance with dissipation, we quantified differential serum protein adsorption behavior because of the chemical components DT, iodinated tyrosine, and PEG: increased PEG content within the polymer structure progressively decreased protein adsorption but the simultaneous presence of both DT and iodinated tyrosine reversed the effects of PEG. The complex interplay of these components was next tested on the adhesion, proliferation, and motility behavior cultured human aortic smooth muscle cells. The incorporation of PEG into the polymer reduced cell attachment, which was reversed in the presence of iodinated tyrosine. Further, we found that as little as 10% DT content was sufficient to negate the PEG effect in polymers containing iodinated tyrosine, whereas in non-iodinated polymers, the PEG effect on cell attachment was reversed. Cross-functional analysis of motility and proliferation revealed divergent substrate chemistry related cell response regimes. For instance, within the series of polymers containing both iodinated tyrosine and 10% of DT, increasing PEG levels lowered smooth muscle cell motility without a change in the rate of cell proliferation. In contrast, for non-iodinated tyrosine and 10% of DT, increasing PEG levels increased cell proliferation significantly while reducing cell motility. Clearly, the polycarbonate polymer library offers a sensitive platform to modulate cell adhesion, proliferation, and motility responses, which, in turn, may have implications for controlling vascular remodeling in vivo. Additionally, our data suggests unique biorelevant properties following the incorporation of iodinated subunits in a polymeric biomaterial as a potential platform for X-ray visible devices.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume93
Issue number2
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

polycarbonate
Cell adhesion
Polycarbonates
Polyethylene glycols
Tyrosine
Muscle
Polymers
Cells
Cell proliferation
Proteins
Adsorption
Biomaterials
Biocompatible Materials
X rays
Functional analysis

Keywords

  • Cell adhesion and motility
  • Iodination
  • Poly(ethylene glycol)
  • Smooth muscle cells
  • Tyrosine-derived polycarbonates
  • Vascular biomaterials

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

Cite this

Interplay of anionic charge, poly(ethylene glycol), and iodinated tyrosine incorporation within tyrosine-derived polycarbonates : Effects on vascular smooth muscle cell adhesion, proliferation, and motility. / Johnson, Patrick A.; Luk, Arnold; Demtchouk, Aleksey; Patel, Hiral; Sung, Hak Joon; Treiser, Matthew D.; Gordonov, Simon; Sheihet, Larisa; Bolikal, Das; Kohn, Joachim; Moghe, Prabhas V.

In: Journal of Biomedical Materials Research - Part A, Vol. 93, No. 2, 01.05.2010, p. 505-514.

Research output: Contribution to journalArticle

Johnson, Patrick A. ; Luk, Arnold ; Demtchouk, Aleksey ; Patel, Hiral ; Sung, Hak Joon ; Treiser, Matthew D. ; Gordonov, Simon ; Sheihet, Larisa ; Bolikal, Das ; Kohn, Joachim ; Moghe, Prabhas V. / Interplay of anionic charge, poly(ethylene glycol), and iodinated tyrosine incorporation within tyrosine-derived polycarbonates : Effects on vascular smooth muscle cell adhesion, proliferation, and motility. In: Journal of Biomedical Materials Research - Part A. 2010 ; Vol. 93, No. 2. pp. 505-514.
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abstract = "Regulation of smooth muscle cell adhesion, proliferation, and motility on biomaterials is critical to the performance of blood-contacting implants and vascular tissue engineering scaffolds. The goal of this study was to examine the underlying substrate-smooth muscle cell response relations, using a selection of polymers representative of an expansive library of multifunctional, tyrosine-derived polycarbonates. Three chemical components within the polymer structure were selectively varied through copolymerization: (1) the content of iodinated tyrosine to achieve X-ray visibility; (2) the content of poly(ethylene glycol) (PEG) to decrease protein adsorption and cell adhesivity; and (3) the content of desaminotyrosyl-tyrosine (DT), which regulates the rate of polymer degradation. Using quartz crystal microbalance with dissipation, we quantified differential serum protein adsorption behavior because of the chemical components DT, iodinated tyrosine, and PEG: increased PEG content within the polymer structure progressively decreased protein adsorption but the simultaneous presence of both DT and iodinated tyrosine reversed the effects of PEG. The complex interplay of these components was next tested on the adhesion, proliferation, and motility behavior cultured human aortic smooth muscle cells. The incorporation of PEG into the polymer reduced cell attachment, which was reversed in the presence of iodinated tyrosine. Further, we found that as little as 10{\%} DT content was sufficient to negate the PEG effect in polymers containing iodinated tyrosine, whereas in non-iodinated polymers, the PEG effect on cell attachment was reversed. Cross-functional analysis of motility and proliferation revealed divergent substrate chemistry related cell response regimes. For instance, within the series of polymers containing both iodinated tyrosine and 10{\%} of DT, increasing PEG levels lowered smooth muscle cell motility without a change in the rate of cell proliferation. In contrast, for non-iodinated tyrosine and 10{\%} of DT, increasing PEG levels increased cell proliferation significantly while reducing cell motility. Clearly, the polycarbonate polymer library offers a sensitive platform to modulate cell adhesion, proliferation, and motility responses, which, in turn, may have implications for controlling vascular remodeling in vivo. Additionally, our data suggests unique biorelevant properties following the incorporation of iodinated subunits in a polymeric biomaterial as a potential platform for X-ray visible devices.",
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