Click hydrogels, microgels and nanogels: Emerging platforms for drug delivery and tissue engineering

The furan/maleimide Diels–Alder reaction: A versatile click–unclick tool in macromolecular synthesis

Degradable and cell-compatible hydrogels can be designed to mimic the physical and biochemical characteristics of native extracellular matrices and provide tunability of degradation rates and related properties under physiological conditions. Hence, such hydrogels are finding widespread application in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled three-dimensional culture, and tissue engineering. Cellular processes, such as adhesion, proliferation, spreading, migration, and differentiation, can be controlled within degradable, cell-compatible hydrogels with temporal tuning of biochemical or biophysical cues, such as growth factor presentation or hydrogel stiffness. However, thoughtful selection of hydrogel base materials, formation chemistries, and degradable moieties is necessary to achieve the appropriate level of property control and desired cellular response. In this review, hydrogel design considerations and materials for hydrogel preparation, ranging from natural polymers to synthetic polymers, are overviewed. Recent advances in chemical and physical methods to crosslink hydrogels are highlighted, as well as recent developments in controlling hydrogel degradation rates and modes of degradation. Special attention is given to spatial or temporal presentation of various biochemical and biophysical cues to modulate cell response in static (i.e., non-degradable) or dynamic (i.e., degradable) microenvironments. This review provides insight into the design of new cell-compatible, degradable hydrogels to understand and modulate cellular processes for various biomedical applications.

https://pubs.rsc.org/en/content/articlepdf/2013/cs/c3cs60040h

Designing degradable hydrogels for orthogonal control of cell microenvironments

Diels–Alder “click” reactions: recent applications in polymer and material science

Natural molecular biomass plays an important role in the field of renewable polymers, as they can be directly used or derivatized as monomers for controlled polymerization, in a way similar to many petroleum-derived monomers. We deliver this perspective primarily based on a monomer approach. Biomass-derived monomers are separated into four major categories according to their natural resource origins: (1) oxygen-rich monomers including carboxylic acids (lactic acid, succinic acid, itaconic acid, and levulinic acid) and furan; (2) hydrocarbon-rich monomers including vegetable oils, fatty acids, terpenes, terpenoids and resin acids; (3) hydrocarbon monomers (bio-olefins); and (4) non-hydrocarbon monomers (carbon dioxide). A variety of emerging synthetic tools (controlled polymerization and click chemistry) are particularly summarized. An overview on future opportunities and challenges, which are critical to promote biorefinery in the production of renewable chemicals and polymers, is given.

Controlled Polymerization of Next-Generation Renewable Monomers and Beyond

Thermosensitive hydrogels synthesized by fast Diels–Alder reaction in water

Facile preparation of poly(N-isopropylacrylamide)-based hydrogels via aqueous Diels–Alder click reaction

Characterisation of N-vinyl-2-pyrrolidone-based hydrogels prepared by a Diels–Alder click reaction in water

Because the properties and applications of hydrogels are determined by the formation principle and conditions of the hydrogels, novel methods for preparing hydrogels have increasingly triggered scientists' interest. Here the Diels–Alder reaction was applied to the preparation of hydrogels. For the resultant polymeric diene and dienophile, the Diels–Alder reaction could be performed in water. The gelation time was found to be closely related to the temperature. The gelation time decreased with the temperature increasing. Moreover, the hydrogels were stable in water, and the retro-Diels–Alder reaction could be performed in N,N-dimethylformamide easily. A study of the swelling ratio indicated that the hydrogels were responsive to the temperature. The hydrogel formation method described here provides several advantages, such as mild reaction conditions, no initiator or catalyst, a tunable gelation rate, and thermal reversibility, and it has great potential for the preparation of biomaterials. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Diels–Alder reaction in water for the straightforward preparation of thermoresponsive hydrogels

The tandem physical and chemical crosslinking was used to prepare injectable hydrogels. First, the terpolymers with diene groups were synthesized by the free radical copolymerization of N-isopropylacrylamide (NIPA), N,N-dimethylacrylamide (DMA) and furfuryl methacrylate (FM). Second, dienophile-functionalized terpolymers were obtained from the terpolymers of NIPA, DMA, and 2-hydroxyethyl methacrylate (HEMA) and N-maleoyl alanine (AMI) by a coupling reaction under N,N′-dicyclohexylcarbodiimide (DCC). When the screened diene-functionalized terpolymer and dienophile-functionalized terpolymer were dissolved separately in water and mixed, physically cross-linked hydrogels formed rapidly within 10 s at 37 °C. Subsequently, the physically crosslinked hydrogels could change gradually into chemically cross-linked hydrogels by a Diels-Alder reaction and the mechanical strength of the hydrogels could be improved. The swelling behavior study suggests that the hydrogels possess thermosensitivity and good reproducibility at different temperatures. The strategy described, i.e. incorporating the advantages of physically crosslinked hydrogels and chemically crosslinked hydrogels, has potential applications in the preparation of injectable hydrogels.

Zhe Yang

Papers

Thermosensitive hydrogels synthesized by fast Diels–Alder reaction in water

Facile preparation of poly(N-isopropylacrylamide)-based hydrogels via aqueous Diels–Alder click reaction

Characterisation of N-vinyl-2-pyrrolidone-based hydrogels prepared by a Diels–Alder click reaction in water

Diels–Alder reaction in water for the straightforward preparation of thermoresponsive hydrogels

Preparation of Thermosensitive Hydrogels by means of Tandem Physical and Chemical Crosslinking