Lessons from nature: stimuli-responsive polymers and their biomedical applications

doi:10.1016/S0167-7799(02)01962-5

Trends in Biotechnology

Volume 20, Issue 7, 1 July 2002, Pages 305-311

https://doi.org/10.1016/S0167-7799(02)01962-5 Get rights and content

Abstract

Response to stimulus is a basic process of living systems. Based on the lessons from nature, scientists have been designing useful materials that respond to external stimuli such as temperature, pH, light, electric field, chemicals and ionic strength. These responses are manifested as dramatic changes in one of the following: shape, surface characteristics, solubility, formation of an intricate molecular self-assembly or a sol-to-gel transition. Applications of stimuli-responsive, or ‘smart’, polymers in delivery of therapeutics, tissue engineering, bioseparations, sensors or actuators have been studied extensively and numerous papers and patents are evidence of rapid progress in this area. Understanding the structure–property relationship is essential for the further development and rational design of new functional smart materials. For example, kinetic and thermodynamic control of the coil-to-globule transition could be achieved through changes in polymer composition and topology.

Section snippets

Copolymers of N-isopropylacrylamide

Important recent advances in PNIPAAm-based systems have focused on mechanistic understanding of phase transition, fine control of the structure–property relationship and novel biomedical applications. PNIPAAm is soluble below 32°C and precipitates above 32°C in water [3]. The phase transition temperature is referred to as lower critical solution temperature (LCST). Below the LCST, favorable interactions via hydrogen bonding between amide groups in polymer and water molecules lead to dissolution

Sol–gel reversible hydrogels

Aqueous solutions of some polymers undergo sol-to-gel transition in response to temperature changes. Therapeutic agents such as drugs, cells or proteins might be mixed in a sol state and injected using a syringe into subcutaneous layers or a diseased site to form a depot system. The minimally invasive, in situ gelling injection system creates an advantageous alternative to surgical procedure. In this section, we focus on in situ gelling poloxamers, PEG–PLGA copolymers and a chitosan–glycerol

pH-sensitive polymers

Polymers containing ionizable functional groups that respond to change in pH are called pH-sensitive polymers. By generating the charge along the polymer backbone, the electrostatic repulsion results in an increase in the hydrodynamic volume of the polymer. Polyacrylic acid, polymethacrylic acid (PMAA), poly(ethylene imine), poly(l-lysine), and poly(N,N-dimethyl aminoethyl methacrylamide) are typical examples of pH-sensitive polymers. When we consider the pH variation in our body, the

Hybrid hyrogels: bridging proteins with synthetic polymers

With current advances in biotechnology, peptides with specific sequences as well as specific secondary structures such as helix, beta turn and so on can be prepared. Peptides undergo conformational changes that might be driven by temperature, pH and specific binding behavior. Coupling of stimuli-sensitive peptide motifs to synthetic polymers or other polypeptides creates stimuli-sensitive hybrid systems. ProLastin, a polypeptide block copolymer composed of silk-like (GAGAGS; hard

Electrosensitive and light-sensitive polymers

Electrosensitive and light-sensitive polymers have been investigated extensively for applications in microsystems, tissue engineering and medical imaging. As an example of recent developments, polythiophene-based conductive polymer gel was shown to undergo swelling–deswelling transition in response to applied potential over −0.8 to 0.5 square wave potential. When confined in a well, the gel developed a pressure of 10 KPa, which can be used in small-scale actuators or valves in microsystems [65]

Conclusions

The recent progress in stimuli-responsive polymers has been discussed. Temperature-, pH-, chemicals- and light-sensitive polymers offer a very exciting field of research, not only from the basic molecular designer viewpoint but also from the perspective of biomedical applications. These polymers might be classified as degradable and nondegradable. When permanent applications in the body or external use such as cell culture matrix, surface modification and sensors are considered, the

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Trends in Biotechnology

ReviewLessons from nature: stimuli-responsive polymers and their biomedical applications

Abstract

Section snippets

Copolymers of N-isopropylacrylamide

Sol–gel reversible hydrogels

pH-sensitive polymers

Hybrid hyrogels: bridging proteins with synthetic polymers

Electrosensitive and light-sensitive polymers

Conclusions

Trends Biotechnol.

Prog. Polym. Sci.

Polymer

Enzyme Microb. Technol.

J. Control. Release

J. Pharm. Sci.

Colloids Surf. B Biointerfaces

J. Control. Release

Biomaterials

J. Control. Release

J. Control. Release

J. Control. Release

Anal. Biochem.

J. Control. Release

Really smart bioconjugates of smart polymers and receptor proteins

J. Biomed. Mater. Res.

Volumetric studies of aqueous polymer solutions using pressure perturbation calorimetry: a new look at the temperature-induced phase transition of poly(N-isopropylacrylamide) in water and D2O

Macromolecules

Direct observation of internal structures in poly(N-isopropylacrylamide) chemical gels

Macromolecules

Thermosensitive micelle forming block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide)

Macromolecules

Novel bifunctional polymer with reactivity and temperature sensitivity

J. Biomater. Sci. Polym. Edn.

Temperature sensitivity of a hydrogel network containing different LCST oligomers grafted to the hydrogel backbone

Polym. Gels Networks

Comb-type grafted hydrogels with rapid deswelling response to temperature changes

Nature

Rapid deswelling response of poly(N-isopropylacrylamide) hydrogels by the formation of water release channels using poly(ethylene oxide) graft chains

Macromolecules

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Thermoreversible gelation of PEG–PLGA–PEG triblock copolymer aqueous solutions

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Thermogelling biodegradable polymers with hydrophilic backbones: PEG-g-PLGA

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Self-assembly in aqueous block copolymer solution

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Review
Lessons from nature: stimuli-responsive polymers and their biomedical applications

Volumetric studies of aqueous polymer solutions using pressure perturbation calorimetry: a new look at the temperature-induced phase transition of poly(N-isopropylacrylamide) in water and D₂O