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Polymers 2018, 10(12), 1314; https://doi.org/10.3390/polym10121314

Switchable Release of Bone Morphogenetic Protein from Thermoresponsive Poly(NIPAM-co-DMAEMA)/Cellulose Sulfate Particle Coatings

1
Leibniz-Institut für Polymerforschung Dresden e.V., Abteilung Polyelektrolyte und Dispersionen, Hohe Straße 6, 01069 Dresden, Germany
2
Technische Universität Dresden, Fachrichtung für Chemie und Lebensmittelchemie, 01062 Dresden, Germany
3
Universität Paderborn, Department Chemie, Organische und Makromolekulare Chemie, Warburger Str. 100, 33098 Paderborn, Germany
4
Medizinische Klinik V, Universitätsklinikum Heidelberg, INF 350, 69120 Heidelberg, Germany
5
Institute of Physical Chemistry, Department of Biophysical Chemistry, Heidelberg University, INF 253, 69120 Heidelberg, Germany
6
Max Planck Institute for Medical Research, Department of Cellular Biophysics and Central Scientific Facility “Cell Biology”, Jahnstr. 29, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Received: 26 October 2018 / Revised: 20 November 2018 / Accepted: 22 November 2018 / Published: 27 November 2018
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Abstract

Thermoresponsive coatings of poly(N-isopropylacrylamide-co-DMAEMA)/cellulose sulfate (PNIPAM-DMAEMA/CS) complexes are reported eluting bone-morphogenetic-protein-2 (BMP-2) on demand relevant for implant assisted local bone healing. PNIPAM-DMAEMA/CS dispersions contained colloid particles with hydrodynamic radii RH = 170–288 nm at T = 25 °C shrinking to RH = 74–103 nm at T = 60 °C. Obviously, PNIPAM-DMAEMA/CS undergoes volume phase transition (VPT) analogously to pure PNIPAM, when critical VPT temperature (VPTT) is exceeded. Temperature dependent turbidity measurements revealed broad VPT and VPTT 47 °C for PNIPAM-DMAEMA/CS colloid dispersions at pH = 7.0. FTIR spectroscopy on thermoresponsive PNIPAM-DMAEMA/CS particle coatings at germanium model substrates under HEPES buffer indicated both wet-adhesiveness and VPT behavior based on diagnostic band intensity increases with temperature. From respective temperature courses empirical VPTT ≈ 42 °C for PNIPAM-DMAEMA/CS coatings at pH = 7.0 were found, which were comparable to VPTT found for respective dispersions. Finally, the PNIPAM-DMAEMA/CS coatings were loaded with BMP-2 and model protein papain (PAP). Time dependent FTIR spectroscopic measurements showed, that for T = 37 °C there was a relative protein release of ≈30% for PAP and ≈10% for BMP-2 after 24 h, which did not increase further. Heating to T = 42 °C for PAP and to 47 °C for BMP-2 further secondary protein release of ≈20% after 24 h was found, respectively, interesting for clinical applications. BMP-2 eluted even at 47 °C was found to be still biologically active. View Full-Text
Keywords: bone healing; protein delivery; polyelectrolyte complex; thermoresponsive polymers; bone morphogenetic protein 2 bone healing; protein delivery; polyelectrolyte complex; thermoresponsive polymers; bone morphogenetic protein 2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Müller, M.; Urban, B.; Reis, B.; Yu, X.; Grab, A.L.; Cavalcanti-Adam, E.A.; Kuckling, D. Switchable Release of Bone Morphogenetic Protein from Thermoresponsive Poly(NIPAM-co-DMAEMA)/Cellulose Sulfate Particle Coatings. Polymers 2018, 10, 1314.

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