Hybrid hydrogels for biomedical applications

Abstract

The use of hydrogels in biomedical applications dates back multiple decades, and the engineering potential of these materials continues to grow with discoveries in chemistry and biology. The approaches have led to increasing complex hydrogels that incorporate both synthetic and natural polymers and functional domains for tunable release kinetics, mediated cell response, and ultimately use in clinical and research applications in biomedical practice. This review focuses on recent advances in hybrid hydrogels that incorporate nano/microstructures, their synthesis, and applications in biomedical research. Examples discussed include the implementation of click reactions, photopatterning, and 3D printing for the facile production of these hybrid hydrogels, the use of biological molecules and motifs to promote a desired cellular outcome, and the tailoring of kinetic and transport behavior through hybrid-hydrogel engineering to achieve desired biomedical outcomes. Recent progress in the field has established promising approaches for the development of biologically relevant hybrid hydrogel materials with potential applications in drug discovery, drug/gene delivery, and regenerative medicine.

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

“…PNIPAM hydrogel is a promising material for drug delivery that can encapsulate drugs easily and give a temperature-dependent drug release in a slow and linear profile [9,[87][88][89]. Recently, PNIPAM-based composite hydrogels have been developed for applications of controlled drug delivery systems, which can overcome the drawbacks of the conventional drug delivery systems by enhancing drug solubility, sustained release time and reducing side effects [14,90,91].…”

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

“…Processing methods include [1]: solution casting/drying, theta gelation, freezing or freezing/pressurizing, freeze drying, emulsion freeze drying, inverse microemulsion polymerization technique, solution blowing, electrospinning, coagulation treatment, CO 2 -in-water emulsion, sol-gel method/thermal annealing, CO 2 bubbles template freeze drying, high hydrostatic pressure [HHP] method, supercritical gel-drying. Other new synthesis methods include the implementation of click chemistry reactions [99], photo-patterning, and rapid prototyping, 3D printing for the facile production of hybrid hydrogels, self-assembly [100,101], the use of biological molecules and motifs to promote a desired cellular outcome, and the tailoring of kinetics and transport behavior to obtain desired biomedical outcomes [102]. 3D bioprinting of hydrogels is performed in accordance with the native tissue architecture therefore it is expected to result in a new generation of engineered tissues.…”

“…Other important applications are [102] Particularized examples of medical applications of hybrid hydrogels are described in the following sections.…”

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

“…Noncovalent interactions include electrostatic interactions such as heparin and heparin binding proteins (Liang and Kiick, 2014;Freudenberg et al, 2016), or hydrophobic associations such as cyclodextrin and hydrophobic drugs (Mateen and Hoare, 2014). Otherwise, covalent interactions can be designed using noncleavable and cleavable linkages between drugs and hydrogels that are incorporated via reactions such as click chemistries (e.g., copper-free click, thiol-ene, Diels-Alder reactions, and oxime and hydrazine ligation) and photochemistries (e.g., nitrobenzyl and coumarin photocleavage reactions); these reactions also are employed for hydrogel crosslinking (Christman et al, 2011;Yigit et al, 2011;Phelps et al, 2012;Ulrich et al, 2014;Kolmel and Kool, 2017;Ruskowitz and DeForest, 2018;Palmese et al, 2019). Thus, the chemical tunability of hydrogels, particularly their mesh size, crosslinking chemistry, and drug interactions, enables fine-tuned control over drug transport through the hydrogel.…”