Methods for producing microstructured hydrogels for targeted applications in biology

Abstract

Hydrogels have been broadly studied for applications in clinically motivated fields such as tissue regeneration, drug delivery, and wound healing, as well as in a wide variety of consumer and industry uses. While the control of mechanical properties and network structures are important in all of these applications, for regenerative medicine applications in particular, matching the chemical, topographical and mechanical properties for the target use/tissue is critical. There have been multiple alternatives developed for fabricating materials with microstructures with goals of controlling the spatial location, phenotypic evolution, and signaling of cells. The commonly employed polymers such as poly(ethylene glycol) (PEG), polypeptides, and polysaccharides (as well as others) can be processed by various methods in order to control material heterogeneity and microscale structures. We review here the more commonly used polymers, chemistries, and methods for generating microstructures in biomaterials, highlighting the range of possible morphologies that can be produced, and the limitations of each method. With a focus in liquidliquid phase separation, methods and chemistries well suited for stabilizing the interface and arresting the phase separation are covered. As the microstructures can affect cell behavior, examples of such effects are reviewed as well.

Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering

“…Hydrogels consist of a cross-linked polymer network, and open spaces (that is, meshes) between polymer chains; the meshes allow for liquid and small solute diffusion. Typical mesh sizes reported for hydrogels range from 5-100 nm, (Garcia and Kiick, 2019 ) and a number of approaches exist to determine the mesh size. Mesh size also play a key role in controlling diffusion and release of the bioactives from hydrogel system (Burczak et al, 1994 ).…”

“…Several methods have been used to generate hydrogels that involve micronized domains such as emulsion stabilization, photopatterning, and liquid-liquid phase separation, rather than the manufacturing and eventual microparticles incorporation in hydrogels (Garcia and Kiick, 2019 ). Although all these techniques can create desirable microstructures with different degrees of control, the phase separation has specific advantages due to the one-step manufacture, specificity of the actions, and tunability (Lau et al, 2018 ).…”

Synthetic biology as driver for the biologization of materials sciences

“…Methods for fabrication and biomedical applications. [ 106 ] ELPs Design and representative biomedical applications of ELPs, focus on tissue engineering and drug delivery [ 100 ] Elastin Elastin-related biomaterials and their benefit on wound healing [ 107 ] ELRs Elastin-like hydrogels for tissue engineering applications, general use in different biomedical fields [ 108 ] Elastin, silk, collagen, resilin Recombinant biomaterials and applications [ 109 ] Elastin, collagen, silk, resilin & -like proteins Proteins in nanomaterials, modular design, applications in tissue engineering and drug delivery [ 110 ] Tropoelastin & resilin Tropoelastin & resilin-based biomaterials, applications in tissue engineering, (composite materials with silk) [ 111 ] RLPs Liquid–liquid phase separation to generate microstructured hydrogels (applications in tissue engineering and drug delivery) [ 112 ] RLPs Genetic control of material properties through modular design of RLPs and via chemical crosslinking (responsiveness to multiple stimuli, mechanical properties, cell adhesion, and proliferation) [ 113 ] RLPs Engineering mechanical properties, self-assembly, and phase separation, autofluorescence (applications as multifunctional materials in tissue engineering or nanomaterials) [ 114 ] β-hairpin, α-helical coiled coil peptides, ELPs, silk fibroin &resilin Hydrogels with (natural/engineered) peptides or proteins in biomedicine [ 115 ] RLPs Elastomeric and cell-adhesive material based on RLPs (potential for growth factor delivery and proteolytic remodeling) [ 116 ] RLPs Hydrogels for tissue engineering [ 117 ] …”

Hybrid hydrogels for biomedical applications

“…Rather than the fabrication and subsequent incorporation of microparticles in hydrogels, a variety of other approaches have been used to produce hydrogels that include micron-sized domains such as liquid-liquid phase separation, emulsion stabilization, and photopatterning [67]. While all of these methods can yield desirable microstructure with various levels of control, the exploitation of phase separation has particular benefits, owing to the one-step fabrication, tunability, and specificity of the behavior [62].…”