A.Kumar et al.Prog.Polym.Sci.32 (2007)1205-1237 1207 SP can be orized into the ive polymers versible collap after an rnal stim us which involves elastin like polymers (ELPs)[21]. The specific LCST of all these different polymeric sible or physical gels,which can be either micro- systems show potential applications in bioengineer- scopic or macroscopic networks and for which ing and biotechnology. swelling behavior is environmentally triggered and On the other hand in a typical pH-sensitive (chain adsorbed or surface-grafted form,where tion/depro the polyme rever s or on charge over the mole atteenerml interfac strongly on the nT nci tor is odified.SPs in a the three fo tion of pH-sensitive polymer tends to be very sharp can be and usually switches within 0.2-0.3 unit of pH.Co conjugated with biomolecules,thereby widening polymers of methylmethacrylate and methacrylic their potential scope of use in many interesting acid undergo sharp conformational transition and ways Biological molecules that may be conjugated collapse at low pH around 5,while co-polymers of with SPs include proteins and oligopeptides,sugars methylmethacrylate dim thy and polys ou lub ightly and DN dru field and magnetic field the els of which lecule hybrid sys 、is able of re onding to can shrink/swell in response to external electric or biological.physical and chemical stimuli.Hoffman magnetic field stimuli.Polythiophene or sulpho- and colleagues have pioneered the work in combin- nated-polystyrene-based conducting polymers have ing SPs with a wide variety of biomolecules [35-38] shown bending in response to external field The The SPs can be conjugated randomly or site magnetic field-responsive ge specifically prot An earlier the biomolecules. ame journal has their b tha ve polymeed for These responses of polymer systems show use. fulness in bio-related applications such as drug delivery [5.22],bioseparation [3].chromatography [4.23,24]and cell culture [25].Some systems have been eloped to combine two or more stimuli system S 26-281 polymers ma M could beppled in order to nsive poly- mer systems [291.Recently.biochemical stimuli have been considered as another strategy,which biochemical agents [32].There is a great Fig.1.Classification of the polymers by their physical form:(i out ainer form chains in solutio where und beyo the an inkedrever ole gels where s For de gh of the and bo chain d or surf grafted form.where the poly rec ent chapters [33.34]. evers collapses on surface.once an externF127 and poly lactic acid-co–poly ethylene glycol– poly lactic acid (PLLA)/PEG/PLLA triblock co￾polymers [20]. Another interesting class of tempera￾ture-responsive polymers have recently emerged which involves elastin like polymers (ELPs) [21]. The specific LCST of all these different polymeric systems show potential applications in bioengineer￾ing and biotechnology. On the other hand in a typical pH-sensitive polymer, protonation/deprotonation events occur and impart the charge over the molecule (generally on carboxyl or amino groups), therefore it depends strongly on the pH. The pH-induced phase transi￾tion of pH-sensitive polymer tends to be very sharp and usually switches within 0.2–0.3 unit of pH. Co￾polymers of methylmethacrylate and methacrylic acid undergo sharp conformational transition and collapse at low pH around 5, while co-polymers of methylmethacrylate with dimethylaminoethyl methacrylate are soluble at low pH but collapse and aggregate under slightly alkaline conditions. Other types of responsive polymers involve electric field [11] and magnetic field [12], the gels of which can shrink/swell in response to external electric or magnetic field stimuli. Polythiophene or sulpho￾nated-polystyrene-based conducting polymers have shown bending in response to external field. The magnetic field-responsive gel which can be obtained by dispersing magnetic colloidal particle in poly (N-isopropylacrylamide-co-poly vinylalcohol) hy￾drogel matrix and get aggregated in external non￾uniform magnetic field [12]. These responses of polymer systems show use￾fulness in bio-related applications such as drug delivery [5,22], bioseparation [3], chromatography [4,23,24] and cell culture [25]. Some systems have been developed to combine two or more stimuli￾responsive mechanisms into one polymer system. For instance, temperature-sensitive polymers may also respond to pH changes [26–28]. Two or more signals could be simultaneously applied in order to induce response in so called dual-responsive poly￾mer systems [29]. Recently, biochemical stimuli have been considered as another strategy, which involves the responses to antigen [30], enzyme [31] and biochemical agents [32]. There is a great deal of literature available about different forms of SP, but it is beyond the scope and aim of the present review to describe it in detail here. For more details, readers are advised to go through some of the recent reviews and book chapters [33,34]. SP can be categorized into three classes according to their physical forms (Fig. 1). They are (i) linear free chains in solution, where polymer undergoes a reversible collapse after an external stimulus is applied, (ii) covalently cross-linked gels and rever￾sible or physical gels, which can be either micro￾scopic or macroscopic networks and for which swelling behavior is environmentally triggered and (iii) chain adsorbed or surface-grafted form, where the polymer reversibly swells or collapses on a surface, converting the interface from hydrophilic to hydrophobic and vice versa, once a specific external parameter is modified. SPs in all the three forms—in solution, as hydrogels and on surfaces can be conjugated with biomolecules, thereby widening their potential scope of use in many interesting ways. Biological molecules that may be conjugated with SPs include proteins and oligopeptides, sugars and polysaccharides, single- and double-stranded oligonucleotides and DNA plasmids, simple lipids and phospholipids, and other recognition ligands and synthetic drug molecules. The polymer–biomo￾lecule hybrid system is capable of responding to biological, physical and chemical stimuli. Hoffman and colleagues have pioneered the work in combin￾ing SPs with a wide variety of biomolecules [35–38]. The SPs can be conjugated randomly or site￾specifically to protein biomolecules. An earlier review published in the same journal has described various forms of stimuli-responsive polymers and their bioconjugates that have been utilized for ARTICLE IN PRESS S T I M U L U S Fig. 1. Classification of the polymers by their physical form: (i) linear free chains in solution where polymer undergoes a reversible collapse after an external stimulus is applied; (ii) covalently cross-linked reversible gels where swelling or shrinking of the gels can be triggered by environmental change; and (iii) chain adsorbed or surface-grafted form, where the polymer reversibly swells or collapses on surface, once an external parameter is changed. A. Kumar et al. / Prog. Polym. Sci. 32 (2007) 1205–1237 1207