Table 1.
Overview of some relevant publications on poly(N-isopropylacrylamide) (PNIPAAm) copolymerization and its biomedical applications over the past 10 years.
| Authors (Year) | Bioapplications (Bio-Area) * | Scientific Innovation | Improvements in the Biomedical Field |
|---|---|---|---|
| Satarkar et al. (2008) [29] | Remote controlled (RC) drug delivery (D.D.) | High-frequency alternating magnetic field (AMF) to trigger the on-demand pulsatile drug release from nanocomposites synthesized by incorporation of superparamagnetic Fe3O4 particles in PNIPAAm gels | Application of AMF resulted in uniform heating within the nanocomposites, leading to accelerated collapse and squeezing out large amounts of imbibed drug (release at a faster rate) |
| Mizutani et al. (2008) [30] | Tissue engineering for endothelial cells (T.E.) | ATRP of PNIPAAm brushes and their influence on the adhesion and the detachment of bovine carotid artery endothelial cells (ECs) | Improvement of surface hydrophilicity, presence of more extended chain conformations with relatively high chain mobility and chain hydration |
| Klaikherd et al. (2009) [31] | Tuning and control of drug delivery (D.D.) | Novel triple stimuli sensitive block assembly that responds to changes in temperature, pH and redox potential | Fine-tuning of the guest molecule release kinetics and possibility of achieving location-specific delivery |
| Tan et al. (2009) [32] | Injectable hydrogel for adipose tissue engineering (T.E./S.C.) | Synthesis of copolymer composed by hyaluronic acid and PNIPAAm (AHA-g-PNIPAAm) | Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were non-cytotoxic and preserved the viability of the entrapped cells |
| Fujimoto et al. (2009) [33] | Injectable hydrogel for ischemic cardiomyopathy (T.E.) | Biodegradable, thermo-responsive hydrogel based on copolymerization of NIPAAm, acrylic acid (AA) and hydroxyethyl methacrylate-poly(trimethylene carbonate) (HEMAPTMC) | Injection of the material prevented ventricular dilation and improved contractile function in a chronic rat infarction model |
| Chen et al. (2009) [34] | Blood-compatible materials (T.E.) | Surface-initiated ATRP for PNIPAAm grafting from silicon nanowire arrays | Largely reduced platelet adhesion in vitro, providing a new strategy for fabricating blood-compatible materials |
| Purushotham et al. (2009) [35] | Anticancer therapy (D.D.) | γ-Fe2O3 iron oxide magnetic nanoparticles (MNP) coated with PNIPAAm and loaded with anti-cancer drug (doxorubicin-(dox)) | Magnetic drug targeting followed by simultaneous hyperthermia and drug release |
| Yoshida (2010) [36] | Biomimetic actuators (B.S.) | Self-oscillating gels driven by the Belousov-Zhabotinsky reaction | Cyclic soluble–insoluble changes or swelling–deswelling changes without any on–off switching of external stimuli |
| Wu et al. (2010) [37] | Cancer cell imaging (D.D./B.I.) | Core-shell structured hybrid nanogels composed of Ag nanoparticle (NP) as core and PNIPAAm-co-acrylic acid gel as shell | Long circulation and specific accumulation on cells (for use as smart dosing of the pathological zones) |
| Stoychev et al. (2011) [38] | Yeast cells release (D.D.) | Star-like patterned polycaprolactone-PNIPAAm bilayers like proof of principle for thermo-responsive self-folding capsules | Reversibly encapsulate/release yeast cells in response to temperature signal |
| Lin et al. (2012) [39] | Cell sheets (S.C.) | Microtextured PNIPAAm-poly(dimethylsiloxane) (PDMS) synthesized by a method suitable for generating aligned vascular smooth muscle cell (VSMC) sheets | Inexpensive, biocompatible, oxygen permeable, and easily microtextured thermo-responsive substrate for producing cell sheets |
| Dai et al. (2012) [40] | In vivo bioimaging and cancer therapy (D.D./B.I.) | Microspheres of NaYF4:Yb3+/Er3+ coated with PNIPAAm-co-(methacrylic acid)] polymer used as carrier for the anticancer drug | Luminescent bioprobes that rapidly release the anticancer drug (doxorubicin hydrochloride, DOX) |
| Zhu et al. (2012) [41] | Nanogels as microfluidic devices (M.F.D.) | Photothermally sensitive PNIPAAm/graphene oxide (PNIPAAm/GO) nanocomposite synthesized by γ-irradiation | Nanocomposite phase transition is completely reversible via laser exposure or non-exposure |
| Yang et al. (2013) [42] | Nanocarriers for RC drug release (D.D.) | Near-infrared (NIR)-stimulus controlled drug release system based on Au-nanocage@mSiO2@PNIPAAm core–shell nanocarrier | Synergistic chemo-photothermal therapy effect that significantly enhances the cancer cell killing efficacy |
| Li et al. (2014) [43] | Stem cell transplantation in myocardial repair (S.C.) | A thermo-sensitive single-wall carbon nanotubes (SWCNTs)-modified PNIPAAm hydrogel (PNIPAAm/SWCNTs) | Enhancement of the engraftment of seeding cells in infarct myocardium |
| Gupta et al. (2014) [22] | Cyto-protective hydrogel for cell encapsulation (D.D.) | ABC triblock polymer poly-[(propylenesulfide)-block-(N,N-dimethylacrylamide)-block-(PNIPAAm)](PPS-b-PDMA-b-PNIPAAm) | Good syneresis, lack of degradability, and lack of inherent drug loading and environmentally responsive release mechanisms |
| Cui et al. (2014) [44] | Injectable hydrogels for cardiac therapy (T.E./S.C.) | Hydrogel composed by PNIPAAm and electroactive tetraaniline (TA) followed by the addition of 2-methylene-1,3-dioxepane (MDO) | 2-Methylene-1,3-dioxepane (MDO) and tetraaniline improves biodegradability, electrical properties, and antioxidant activities |
| Li et al. (2015) [45] | Self-healing hydrogel (T.E.) | Mussel-inspired tri-block copolymer PNIPAAm-co-(N-3,4-dihydroxyphenethyl acrylamide)]-b-poly(ethylene oxide) | Automatic healing from repeated structural damage and effective prevention of non-specific cell attachment and biofilm formation |
| Bakarich et al. (2015) [46] | Thermally actuating hydrogel for smart valves (T.E./B.S.) | 4D Printing of hydrogels made by interpenetrating network of alginate and PNIPAAm | Mechanically robust and thermally actuating 4D printed smart valve |
| Kesti et al. (2015) [47] | Bioink for articular cartilage (T.E.) | Blending of PNIPAAm grafted hyaluronan (HA-PNIPAAm) with methacrylated hyaluronan (HAMA) | High-resolution scaffolds with good viability printed layer-by-layer |
| Psarra et al. (2015) [48] | Protein adsorption and cell adhesion (T.E.) | Nanostructures of PNIPAAm (homo) and PNIPAAm-co-acrylic acid (binary) by atom transfer radical polymerization (ATRP) and investigation of the fibrinogen (FGN) adsorption responsiveness | Terminal hydrophobic moieties improved wettability, lower critical solution temperature (LCST), and morphology of both brush systems with consequent alteration of FGN adsorption |
| Lima et al. (2016) [49] | Ocular biocompatibility (T.E.) | Study of the safety of intravitreal injections of poly-N-isopropylacrylamide (PNIPAAm) tissue adhesive in rabbit eyes | Intravitreal injections of PNIPAAm were nontoxic in this animal study |
| Li et al. (2016) [50] | Stem-cell carriers for cardiac therapy (S.C.) | Free-radical polymerization of NIPAAm, propylacrylic acid, hydroxyethyl methacrylate-co-oligo(trimethylene carbonate), and methacrylate poly(ethylene oxide) methoxy ester | Innovative hydrogels that quickly solidify at the pH of an infarcted heart but cannot solidify at the pH of blood injectable through catheters, commonly used for minimally invasive surgeries |
| Zhao et al. (2017) [51] | Cell-inspired biointerface for use in immunoassays in blood (T.E./B.S.) | Biointerfaces constructed by patterning smart hydrogels poly(N-isopropylacrylamide-co-sodium acrylate) (PNIPAAm-co-PNaAc) on hydrophilic layers (poly(ethylene glycol), PEG), followed by immobilization of antibodies on the patterned hydrogels | Versatile and effective biointerfaces for antibody–antigen recognition, which offers a potential new approach for developing highly sensitive immunoassays in blood |
| Zubik et al. (2017) [52] | Wound dressing (T.E.) | PNIPAAm reinforced with cellulose nanocrystals (CNCs); for wound dressing purposes, metronidazole was used as a target drug | Injectable hydrogels as promising materials for wound dressing |
| Liu et al. (2018) [53] | Photosensitizer for cancer treatment (D.D.) | A novel comb-shaped porphyrin end-functionalized poly(NIPAAm)-b-poly[oligo (ethylene glycol methyl ether methacrylate)] | Photo-toxicity toward HeLa cancer cells and local accumulation on tumor tissues: photosensitizer in photodynamic anticancer therapy |
* Notes: Abbreviations for the bio-area of PNIPAAm studies: Drug Delivery (D.D.); Tissue Engineering (T.E.); Bio-Sensor (B.S.); Bio-Imaging (B.I.); Microfluidic Devices (M.F.D.).