Poly(N-isopropylacrylamide)-Based Thermoresponsive Composite Hydrogels for Biomedical Applications

Abstract

Poly(N-isopropylacrylamide) (PNIPAM)-based thermosensitive hydrogels demonstrate great potential in biomedical applications. However, they have inherent drawbacks such as low mechanical strength, limited drug loading capacity and low biodegradability. Formulating PNIPAM with other functional components to form composited hydrogels is an effective strategy to make up for these deficiencies, which can greatly benefit their practical applications. This review seeks to provide a comprehensive observation about the PNIPAM-based composite hydrogels for biomedical applications so as to guide related research. It covers the general principles from the materials choice to the hybridization strategies as well as the performance improvement by focusing on several application areas including drug delivery, tissue engineering and wound dressing. The most effective strategies include incorporation of functional inorganic nanoparticles or self-assembled structures to give composite hydrogels and linking PNIPAM with other polymer blocks of unique properties to produce copolymeric hydrogels, which can improve the properties of the hydrogels by enhancing the mechanical strength, giving higher biocompatibility and biodegradability, introducing multi-stimuli responsibility, enabling higher drug loading capacity as well as controlled release. These aspects will be of great help for promoting the development of PNIPAM-based composite materials for biomedical applications.

Keywords: biomedical applications; hydrogels; mechanical strength; poly(N-isopropylacrylamide) (PNIPAM); thermosensitivity.

Scheme 1

The application areas of Poly(N-isopropylacrylamide) (PNIPAM)-based composite hydrogels as well as the required properties that can be modulated by composite formulation.

Figure 1

Schematic representation of the structures of (A) pure PNIPAM and (B) GO/PNIPAM composite gels. (C) Equilibrium mass swelling degree in pure water at 20 °C and the elastic modulus of GO/PNIPAM composite gels. Adapted with permission from Ref. [72]. Copyright (2016) The Royal Society of Chemistry. Note that in the source article, PNIPAM is referred to as PNIPA.

Figure 2

(A) Preparation of the thermoreversible peptide/PNIPAM mixed hydrogels and loading of antibacterial peptide G(IIKK)₃I-NH₂ for controlled release. (B) Schematic diagrams of the proposed states of the I₃K/PNIPAM networks at temperature either below or above the PNIPAM LCST. Adapted with permission from Ref. [92]. Copyright (2019) American Chemical Society.

Figure 3

(A) Formation of (a) baicaleinliposome (BL) cystic structures and (B) chitosan-coated baicalein liposomes. Adapted with permission from Ref. [94]. Copyright (2018) John Wiley and Sons Ltd.

Figure 4

(A) Schematic illustration of approaches to make injectable hydrogels for cartilage- and bone tissue-engineering applications. Adapted with permission from Ref. [113]. Copyright (2017) Nature Publishing Group. (B) The synthetic routes of NIPAAm-g-Chitosan copolymer and its thiolation as well as the temperature-triggered gelation by disulfide bond formation. Adapted with permission from Ref. [44]. Copyright (2018) Elsevier Ltd.

Figure 5

(A) Schematic illustration of the formation of the f-BNNS/clay/PNIPAM ternary network hydrogel. (B) Hydrogel adhesion on the arm, aluminum, copper, iron, plastics, glasses, polythene and rubbers. Adapted with permission from Ref. [133]. Copyright (2018) The Royal Society of Chemistry.