Thermoresponsive nanocomposite hydrogels with cell-releasing behavior Yaping Hou a , Andrew R. Matthews a , Ashley M. Smitherman a , Allen S. Bulick b , Mariah S. Hahn b , Huijie Hou c , Arum Han c , Melissa A. Grunlan a, * a Department of Biomedical Engineering, Texas A&M University, 337 Zachry Engineering Center, MS 3120, College Station, TX 77843-3120, USA b Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3120, USA c Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843-3120, USA article info Article history: Received 29 January 2008 Accepted 1 April 2008 Available online 2 May 2008 Keywords: Hydrogel Thermally responsive material Siloxane Nanoparticles Cell adhesion Photopolymerization abstract Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels become more hydrophobic when they reversibly switch from a water-swollen to a deswollen state above the volume phase transition temperature (VPTT, w33  C) which has been used to modulate cell adhesion. In the current work, we prepared novel ther- moresponsive nanocomposite hydrogels comprised of a PNIPAAm hydrogel matrix and polysiloxane colloidal nanoparticles (w220 nm average diameter) via in situ photopolymerization of aqueous solutions of NIPAAm monomer, N,N 0 -methylenebisacrylamide (BIS, crosslinker), photoinitiator and polysiloxane nanoparticles (0.5–2.0 wt% based on solution weight) at w7  C. The VPTT of the nanocomposite hydrogels is not altered versus the pure PNIPAAm hydrogel. Dynamic mechanical analysis and tensile tests revealed that higher nanoparticle content generally produced improved hydrogel mechanical properties. Surfaces of nanocomposite hydrogels became increasingly more hydrophobic at all temperatures between 10 and 40  C as the amount of hydrophobic polysiloxane nanoparticles was increased. When cooled from 37 to 25  C, mouse smooth muscle precursor cells (10T1/2) were effectively detached from nanocomposite hydrogel surfaces. The utility of photopatterning to create surface micropillars comprised of nano- composite hydrogels was demonstrated. Published by Elsevier Ltd. 1. Introduction Materials which reversibly switch from a hydrophilic to hydro- phobic state in aqueous media in response to an external stimulus are of interest for creating ‘‘smart’’ or ‘‘intelligent’’ biomedical materials [1]. Thermoresponsive hydrogels are crosslinked, three- dimensional polymer networks that reversibly swell with and then expel aqueous media in response to temperature changes. Ther- moresponsive hydrogels may be prepared by crosslinking polymers which exhibit a lower critical solubility temperature (LCST) [1,2]. Most widely studied is poly(N-isopropylacrylamide) (PNIPAAm) (LCST, w32  C) which is soluble in water below the LCST and re- versibly insoluble above the LCST [3]. Crosslinked PNIPAAm hydrogels undergo a reversible volume phase transition in water from a swollen state to a deswollen state above their volume phase transition temperature (VPTT, w33  C) [4,5]. Thus, surfaces of PNIPAAm hydrogels [6–8] as well as those comprised of covalently grafted PNIPAAm chains [8–10] undergo a large discontinuous change from a hydrophilic to a hydrophobic state when heated above the phase transition temperature. The thermal modulation of hydrophilic/hydrophobic surface properties of PNIPAAm systems is useful for the controlled de- tachment of cultured cells [11,12]. In this way, confluent cell sheets useful for tissue engineering may be detached from culture without enzymes or chelating agents known to damage cells [13]. Cells generally adhere and proliferate more readily on polymeric mate- rials with hydrophobic surfaces rather than hydrophilic surfaces [14–23]. Often characterized by contact angle measurements, polymer surfaces displaying water contact angles greater than 90  are generally considered to be hydrophobic [24]. Several studies have shown that cell adhesion is maximized on moderately hydro- phobic surfaces displaying a water contact angle between 40 and 70  [18–23]. Thus, at w37  C (above the LCST), PNIPAAm-grafted sur- faces are relatively hydrophobic and various types of cells grow well. However, upon cooling below 32  C (below the LCST), they become more hydrophilic and cells spontaneously detach without damaging the cells [25–29]. Similarly, cells may be detached from the surfaces of PNIPAAm hydrogels after cooling below the VPTT [30,31]. Extending the utility of PNIPAAm hydrogels as robust cell-re- leasing materials for tissue culture substrates [11,12], anti-fouling coatings [32–34], or ‘‘self-cleaning’’ implanted sensor membranes [35,36] requires improvement of their poor mechanical properties as well as tailoring the changes in surface hydrophilicity/hydro- phobicity. Hybrid materials prepared from inorganic and organic * Corresponding author. Tel.: þ1 979 845 2406; fax: þ1 979 845 4450. E-mail address: mgrunlan@tamu.edu (M.A. Grunlan). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Published by Elsevier Ltd. doi:10.1016/j.biomaterials.2008.04.024 Biomaterials 29 (2008) 3175–3184