Nanocomposite hydrogels for biomedical applications

Abstract

Hydrogels mimic native tissue microenvironment due to their porous and hydrated molecular structure. An emerging approach to reinforce polymeric hydrogels and to include multiple functionalities focuses on incorporating nanoparticles within the hydrogel network. A wide range of nanoparticles, such as carbon-based, polymeric, ceramic, and metallic nanomaterials can be integrated within the hydrogel networks to obtain nanocomposites with superior properties and tailored functionality. Nanocomposite hydrogels can be engineered to possess superior physical, chemical, electrical, and biological properties. This review focuses on the most recent developments in the field of nanocomposite hydrogels with emphasis on biomedical and pharmaceutical applications. In particular, we discuss synthesis and fabrication of nanocomposite hydrogels, examine their current limitations and conclude with future directions in designing more advanced nanocomposite hydrogels for biomedical and biotechnological applications.

Keywords: biomedical applications; drug delivery; nanocomposite hydrogels; nanoparticles; tissue engineering.

Figure 1

Number of publications related to (a) hydrogels and (b) nanocomposite hydrogels according to ISI Web of Science (data obtained November 2013). A steady increase in the number of publication indicates growing interest in the field of nancomposite hydrogels.

Figure 2

Engineered nanocomposite hydrogels. A range of nanoparticles such as carbon-based nanomaterials, polymeric nanoparticles, inorganic nanoparticles, and metal/metal-oxide nanoparticles are combined with the synthetic or natural polymers to obtain nanocomposite hydrogels with desired property combinations. These nanocomposite networks are either physically or chemically crosslinked. By controlling the polymer-polymer or polymer-nanoparticles interactions, the physical, chemical, and biological properties of the nanocomposite hydrogels can be tailored.

Figure 3

Nanocomposite hydrogels from CNTs and GelMA. a: Schematic showing synthesis of nanocomposite network. First, CNTs are coated with GelMA and then the composite is subjected to UV radiation to obtain photocrosslinked network. b: Due to photocrosslinking ability of the nanocomposite network, microfabrication technologies can be used to control cellular interactions. c: Cardiac cells that were seeded on CNTs-GelMA nanocomposites retained their phenotype as determined by the expression of sarcomeric α-actinin and troponin I. d: The engineered cardiac patch obtained by seeding cardiac cells on CNTs-GelMA surface showed macroscopic mechanical displacement due to continuous contraction and relaxation of the patch. Adapted with permission from Shin et al. (2011, . Copyright (2013) American Chemical Society.

Figure 4

Nanocomposite hydrogels from hyperbranched polyester (HPE) nanoparticles. a: HPE nanoparticles are surface functionalized with photocrosslinkable moieties. When the precursor solution containing functionalized HPE and photoinitiator is subjected to UV radiation, a covalently crosslinked network is obtained. This covalently crosslinked hydrogel is mechanically stable and can maintain its shape in physiological conditions. b: Due to the presence of hydrophobic cavities within the HPE nanoparticles, hydrophobic drugs such as dexamethasone can be entrapped. A sustain release of drug from the hydrogels network was observed over a week. c: By controlling the crosslinking density of the HPE hydrogels, physical properties and cell adhesion characteristics can be tuned. d: Photolithography technique can be used to fabricated micropatterned hydrogel structure to control the cellular interactions. Adapted with permission from Zhang et al. (2013). Copyright (2011) American Chemical Society.

Figure 5

Highly elastomeric hydrogel network was obtained from PEG-Silicate nanocomposites. a: Precursor solution containing silicate nanoplatelets and acrylated PEG when subjected to UV radiation results in the formation of a covalently crosslinked nanocomposite network. The nanocomposite hydrogels stick to soft tissues (b) and undergoes high deformation (c) and (d). e: The addition of synthetic silicate results in significant increase in mechanical stiffness and elongation of the nanocomposite network compared to polymeric hydrogels. f: Moreover addition of silicate also promotes cells adhesion on the nanocomposite hydrogels. Adapted with permission from Gaharwar et al. (2011b). Copyright (2013), with permission from Elsevier.

Figure 6

Nanocomposite hydrogels containing gold nanowire and alginate. a: The distribution of gold nanowires determined using TEM indicates an average length of ~1 μm and an average diameter of 30 nm. The uniform distribution of nanowire within the alginate scaffolds was also observed. b: The topographic mapping of nanocomposite detects the presence of nanowires. In nanocomposite, the current increased with bias voltage over the range −1 to 1V, while negligible current was passed through alginate (without nanowire) over that same range. c: Calcium transient was determined at various locations using calcium dye. The number indicates location of on the Alg-gold nanowire scaffold and the corresponding curves indicate calcium transport at those points. Adapted with permission from Dvir et al. (2011). Copyright (2013) Nature.