Focus Article
Recent development of antifouling polymers: structure, evaluation, and biomedical applications in nano/micro-structures Lingyun Liu,∗ Wenchen Li and Qingsheng Liu Antifouling polymers have been proven to be vital to many biomedical applications such as medical implants, drug delivery, and biosensing. This review covers the major development of antifouling polymers in the last 2 decades, including the material chemistry, structural factors important to antifouling properties, and how to challenge or evaluate the antifouling performances. We then discuss the applications of antifouling polymers in nano/micro-biomedical applications in the form of nanoparticles, thin coatings for medical devices (e.g., artificial joint, catheter, wound dressing), and nano/microscale fibers. © 2014 Wiley Periodicals, Inc. How to cite this article:
WIREs Nanomed Nanobiotechnol 2014, 6:599–614. doi: 10.1002/wnan.1278
INTRODUCTION
A
ntifouling materials, which can resist adsorption of biomolecules, cells, and microorganisms, are critical to many biomedical and engineering applications such as medical implants, drug delivery, biosensing, bioseparation, and marine coatings.1–7 Surfaces or materials that resist biofouling have been described with different terms in current literature, including ‘nonfouling’, ‘superlow fouling’, ‘ultra-low fouling’, ‘low fouling’, ‘antifouling’, or ‘bioinert’. In this review, the term ‘antifouling’ is used to illustrate materials that can prevent the undesirable adhesion from proteins, cells, or microorganisms. This article will first briefly go over the available antifouling materials, discuss structural factors (other than material composition) critical to antifouling performances, followed by how to evaluate antifouling performances (i.e., challenge the antifouling materials). Second part of the article focuses on the applications of antifouling materials in nano- or micro-biomedical engineering. The review focuses ∗ Correspondence
to: [email protected]
Department of Chemical and Biomolecular Engineering, University of Akron, Akron, OH, USA Conflict of interest: The authors have declared no conflicts of interest for this article.
Volume 6, November/December 2014
on the practical aspects and nano/micro-biomedical applications of antifouling polymers from an experimentalist’s point of view. For reviews more toward particular types of antifouling materials or antifouling mechanisms, readers can refer to references.4,8–10
MATERIAL CHEMISTRY (TYPE OF MATERIALS) Surface hydration is commonly considered the key to the antifouling performances of polymers.4,10 On the basis of how the materials interact with water, antifouling polymers are generally classified into two types, hydrophilic polymer and zwitterionic polymer. The hydrophilic polymers interact with water via hydrogen bond, whereas the zwitterionic polymers interact with water via ionic bond. Typical functional groups responsible for the fouling resistance of hydrophilic antifouling polymers are ether, hydroxyl, amide, peptoid, 𝛽-peptoid, and open-ring oxazoline (Figure 1). Antifouling polymers of this type include ethylene glycol-based polymers,11–15 poly(2-hydroxyethyl methacrylate) (pHEMA),16,17 poly(hydroxypropyl methacrylate) (pHPMA),17,18 polysaccharides such as dextran and cellulose,19–22 polyacrylamide,23 polypeptoids,24–26 poly(𝛽-peptoid)s,27,28 and polyalkyloxazoline.29–31
© 2014 Wiley Periodicals, Inc.
599
wires.wiley.com/nanomed
Focus Article
Hydroxyl
OH
Ether
CH2
Amide
C
CH2
O
NH2
C
O Peptoid
NH
O
C
CH2
N
R = methyl hydroxyethyl
R
O
CH3 CH2
hydroxypropyl
CH2
CH2 CH
OH OH
CH3 β-peptoid
CH2
C O
Oxazoline (open ring)
N
R = methyl, ethyl
R CH2
N C
2
CH2
R = methyl, ethyl, propyl
O
R
FIGURE 1 | Typical hydrophilic functional groups that provide fouling resistance.
The antifouling functional groups could be a part of the polymer backbone or the side chain. Zwitterionic groups that provide antifouling properties of zwitterionic polymers include betaine (with positive and negative charges in series on the same side chain), equimolar mixed cationic-anionic pairs (with positive and negative charges on two different side chains), and Bingdi cationic-anionic pairs (with positive and negative charges in parallel on the same side chain) (Figure 2). The word ‘Bingdi’ originates from Chinese Bingdi lotuses which have two flowers in one stalk. Three mostly widely studied betaines are sulfobetaine (SB), carboxybetaine (CB), and phosphorylcholine (PC). Antifouling polymers of zwitterionic type include poly(carboxybetaine methacrylate) poly(sulfobetaine methacrylate) (pCBMA),32,33 (pSBMA),32,34 poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC),35,36 poly(serine methacrylate) (pSerMA),37 poly(lysine methacrylamide) (pLysAA),38 poly(ornithine methacrylamide) (pOrnAA),38 and polyampholyte mixed-charge copolymers composed of positively charged quaternary amine monomers (e.g., [2-(acryloyloxy) ethyl] trimethyl ammonium chloride, or [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride) and negatively charged monomers (e.g., 2-carboxy ethyl acrylate, or 3-sulfopropyl methacrylate potassium salt).39–41 600
Some antifouling polymers possess antifouling functional groups of both types.42,43 For example, poly(carboxybetaine acrylamide) (pCBAA) have both zwitterionic CB and hydrophilic amide groups. The optimized pCBAA-grafted film can achieve close-to-zero (
Recent development of antifouling polymers: structure, evaluation, and biomedical applications in nano/micro-structures Lingyun Liu,∗ Wenchen Li and Qingsheng Liu Antifouling polymers have been proven to be vital to many biomedical applications such as medical implants, drug delivery, and biosensing. This review covers the major development of antifouling polymers in the last 2 decades, including the material chemistry, structural factors important to antifouling properties, and how to challenge or evaluate the antifouling performances. We then discuss the applications of antifouling polymers in nano/micro-biomedical applications in the form of nanoparticles, thin coatings for medical devices (e.g., artificial joint, catheter, wound dressing), and nano/microscale fibers. © 2014 Wiley Periodicals, Inc. How to cite this article:
WIREs Nanomed Nanobiotechnol 2014, 6:599–614. doi: 10.1002/wnan.1278
INTRODUCTION
A
ntifouling materials, which can resist adsorption of biomolecules, cells, and microorganisms, are critical to many biomedical and engineering applications such as medical implants, drug delivery, biosensing, bioseparation, and marine coatings.1–7 Surfaces or materials that resist biofouling have been described with different terms in current literature, including ‘nonfouling’, ‘superlow fouling’, ‘ultra-low fouling’, ‘low fouling’, ‘antifouling’, or ‘bioinert’. In this review, the term ‘antifouling’ is used to illustrate materials that can prevent the undesirable adhesion from proteins, cells, or microorganisms. This article will first briefly go over the available antifouling materials, discuss structural factors (other than material composition) critical to antifouling performances, followed by how to evaluate antifouling performances (i.e., challenge the antifouling materials). Second part of the article focuses on the applications of antifouling materials in nano- or micro-biomedical engineering. The review focuses ∗ Correspondence
to: [email protected]
Department of Chemical and Biomolecular Engineering, University of Akron, Akron, OH, USA Conflict of interest: The authors have declared no conflicts of interest for this article.
Volume 6, November/December 2014
on the practical aspects and nano/micro-biomedical applications of antifouling polymers from an experimentalist’s point of view. For reviews more toward particular types of antifouling materials or antifouling mechanisms, readers can refer to references.4,8–10
MATERIAL CHEMISTRY (TYPE OF MATERIALS) Surface hydration is commonly considered the key to the antifouling performances of polymers.4,10 On the basis of how the materials interact with water, antifouling polymers are generally classified into two types, hydrophilic polymer and zwitterionic polymer. The hydrophilic polymers interact with water via hydrogen bond, whereas the zwitterionic polymers interact with water via ionic bond. Typical functional groups responsible for the fouling resistance of hydrophilic antifouling polymers are ether, hydroxyl, amide, peptoid, 𝛽-peptoid, and open-ring oxazoline (Figure 1). Antifouling polymers of this type include ethylene glycol-based polymers,11–15 poly(2-hydroxyethyl methacrylate) (pHEMA),16,17 poly(hydroxypropyl methacrylate) (pHPMA),17,18 polysaccharides such as dextran and cellulose,19–22 polyacrylamide,23 polypeptoids,24–26 poly(𝛽-peptoid)s,27,28 and polyalkyloxazoline.29–31
© 2014 Wiley Periodicals, Inc.
599
wires.wiley.com/nanomed
Focus Article
Hydroxyl
OH
Ether
CH2
Amide
C
CH2
O
NH2
C
O Peptoid
NH
O
C
CH2
N
R = methyl hydroxyethyl
R
O
CH3 CH2
hydroxypropyl
CH2
CH2 CH
OH OH
CH3 β-peptoid
CH2
C O
Oxazoline (open ring)
N
R = methyl, ethyl
R CH2
N C
2
CH2
R = methyl, ethyl, propyl
O
R
FIGURE 1 | Typical hydrophilic functional groups that provide fouling resistance.
The antifouling functional groups could be a part of the polymer backbone or the side chain. Zwitterionic groups that provide antifouling properties of zwitterionic polymers include betaine (with positive and negative charges in series on the same side chain), equimolar mixed cationic-anionic pairs (with positive and negative charges on two different side chains), and Bingdi cationic-anionic pairs (with positive and negative charges in parallel on the same side chain) (Figure 2). The word ‘Bingdi’ originates from Chinese Bingdi lotuses which have two flowers in one stalk. Three mostly widely studied betaines are sulfobetaine (SB), carboxybetaine (CB), and phosphorylcholine (PC). Antifouling polymers of zwitterionic type include poly(carboxybetaine methacrylate) poly(sulfobetaine methacrylate) (pCBMA),32,33 (pSBMA),32,34 poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC),35,36 poly(serine methacrylate) (pSerMA),37 poly(lysine methacrylamide) (pLysAA),38 poly(ornithine methacrylamide) (pOrnAA),38 and polyampholyte mixed-charge copolymers composed of positively charged quaternary amine monomers (e.g., [2-(acryloyloxy) ethyl] trimethyl ammonium chloride, or [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride) and negatively charged monomers (e.g., 2-carboxy ethyl acrylate, or 3-sulfopropyl methacrylate potassium salt).39–41 600
Some antifouling polymers possess antifouling functional groups of both types.42,43 For example, poly(carboxybetaine acrylamide) (pCBAA) have both zwitterionic CB and hydrophilic amide groups. The optimized pCBAA-grafted film can achieve close-to-zero (
