Synthesis, characterization, and in vitro cell culture viability of degradable poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)- based polymers and crosslinked gels

Daniel J. Siegwart, Sidi A. Bencherif, Abiraman Srinivasan, Jeffrey O. Hollinger, Krzysztof Matyjaszewski

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane) (poly(NIPAAm-co-BMDO)) was synthesized by atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Using UV-vis spectroscopy, the lower critical solution temperature (LCST) of poly (NIPAAm) and poly(NIPAAm-co-BMDO) copolymers were measured, varying with respect to the amount of incorporated BMDO. This material is degradable and possesses a LCST above room temperature and below body temperature, making it a potential candidate for use as an injectable tissue engineering scaffold to enhance fracture repair. ATRP and RAFT enabled preparation of polymers with control over molecular weight up to Mn = 50,000 g/mol and Mw/Mn < 1.2. Degradation studies were performed in basic solution and in complete Dulbecco's modified Eagle medium. The cytotoxicity of the material and its degradation products were analyzed by in vitro cell culture analyses, including cytotoxicity live/dead and CyQUANT cell proliferation assays. Cross-linked scaffolds with degradable units within the polymer backbone and at the crosslinking sites were prepared using an ester-containing diacrylate crosslinker. Furthermore, incorporation of a GRGDS peptide sequence improved cell attachment to the gels. Controlled/living radical polymerization techniques allow for precise control over macromolecular structure and are poised to become powerful tools for tissue engineering scaffold synthesis.

Original languageEnglish (US)
Pages (from-to)345-358
Number of pages14
JournalJournal of Biomedical Materials Research - Part A
Volume87
Issue number2
DOIs
StatePublished - Nov 2008

Fingerprint

Cell culture
Polymers
Scaffolds (biology)
Gels
Tissue Scaffolds
Atom transfer radical polymerization
Cytotoxicity
Tissue engineering
glycyl-arginyl-glycyl-aspartyl-serine
Degradation
Temperature
Living polymerization
Bioelectric potentials
Cell proliferation
Free radical polymerization
Ultraviolet spectroscopy
Crosslinking
Peptides
Assays
Esters

Keywords

  • Atom transfer radical polymerization (ATRP)
  • Biodegradation
  • Crosslinked gels
  • Cytotoxicity
  • Degradable polymers
  • Poly(N-isopropylacrylamide) (PNIPAAm)
  • Reversible addition- fragmentation chain-transfer (RAFT) polymerization
  • Tissue engineering

ASJC Scopus subject areas

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

Cite this

Synthesis, characterization, and in vitro cell culture viability of degradable poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)- based polymers and crosslinked gels. / Siegwart, Daniel J.; Bencherif, Sidi A.; Srinivasan, Abiraman; Hollinger, Jeffrey O.; Matyjaszewski, Krzysztof.

In: Journal of Biomedical Materials Research - Part A, Vol. 87, No. 2, 11.2008, p. 345-358.

Research output: Contribution to journalArticle

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T1 - Synthesis, characterization, and in vitro cell culture viability of degradable poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)- based polymers and crosslinked gels

AU - Siegwart, Daniel J.

AU - Bencherif, Sidi A.

AU - Srinivasan, Abiraman

AU - Hollinger, Jeffrey O.

AU - Matyjaszewski, Krzysztof

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AB - Poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane) (poly(NIPAAm-co-BMDO)) was synthesized by atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Using UV-vis spectroscopy, the lower critical solution temperature (LCST) of poly (NIPAAm) and poly(NIPAAm-co-BMDO) copolymers were measured, varying with respect to the amount of incorporated BMDO. This material is degradable and possesses a LCST above room temperature and below body temperature, making it a potential candidate for use as an injectable tissue engineering scaffold to enhance fracture repair. ATRP and RAFT enabled preparation of polymers with control over molecular weight up to Mn = 50,000 g/mol and Mw/Mn < 1.2. Degradation studies were performed in basic solution and in complete Dulbecco's modified Eagle medium. The cytotoxicity of the material and its degradation products were analyzed by in vitro cell culture analyses, including cytotoxicity live/dead and CyQUANT cell proliferation assays. Cross-linked scaffolds with degradable units within the polymer backbone and at the crosslinking sites were prepared using an ester-containing diacrylate crosslinker. Furthermore, incorporation of a GRGDS peptide sequence improved cell attachment to the gels. Controlled/living radical polymerization techniques allow for precise control over macromolecular structure and are poised to become powerful tools for tissue engineering scaffold synthesis.

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KW - Cytotoxicity

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KW - Tissue engineering

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