Hydrogels for tissue engineering: scaffold design variables and applications.

Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.

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Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology†

Following Sharpless' visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol-ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol-ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.

Thiol–Ene Click Chemistry

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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Hydrogels in regenerative medicine

This work investigates the cytocompatibility of several photoinitiating systems for potential cell encapsulation applications. Both UV and visible light initiating schemes were examined. The UV photoinitiators included 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184), 2-methyl-1-[4-(methylthio) phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure 907), and 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Darocur 2959). The visible light initiating systems included camphorquinone (CQ) with ethyl 4-N, N-dimethylaminobenzoate (4EDMAB) and triethanolamine (TEA) and the photosensitizer isopropyl thioxanthone. A cultured fibroblast cell line, NIH/3T3, was exposed to the photoinitiators at varying concentrations from 0.01% (w/w) to 0.1% (w/w) with and without the presence of initiating light. The results demonstrated that at low photoinitiator concentrations (6 0.01% (w/w)), all of the initiator molecules were cytocompatible with the exception of CQ, Irgac...

Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro

Synthetic hydrogels with engineered, cell-mediated degradation sites are an important category of biomimetic materials. Here, hydrogels are synthesized by a step-growth reaction mechanism via a radically mediated thiol-norbornene (thiol-ene) photopolymerization. This reaction combines the advantages of ideal, homogeneous polymer network formation, facile incorporation of peptides without post-synthetic modification, and spatial and temporal control over the network evolution into a single system to produce proteolytically degradable poly(ethylene glycol) (PEG) peptide hydrogels. Using a thiol-ene photopolymerization, rapid gelation times are achieved, while maintaining high cell viability for cell encapsulation. The enzyme- and cellresponsive characteristics are demonstrated by tailoring the rate of spreading of human mesenchymal stem cells (hMSCs) through both the selection of proteolytically degradable crosslinkers and the density of the adhesion peptide RGDS. Furthermore, cellular function is manipulated spatially within the thiol-ene hydrogels through biochemical photopatterning. The high degree of spatial and temporal control over gelation, combined with robust material properties, makes thiol-ene hydrogels an excellent tool for a variety of medical and biological applications.

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A Versatile Synthetic Extracellular Matrix Mimic via Thiol‐Norbornene Photopolymerization

Synthetic hydrogel niches that promote hMSC viability.

Hydrogels have been used in biology and medicine for many years, and they possess many properties that make them advantageous for tissue engineering applications. Their high water content and tissue-like elasticity are similar to the native extracellular matrix of many tissues. In this work, we investigated the potential of a modified poly(vinyl alcohol) (PVA) hydrogel as a biomaterial for tissue engineering applications. First, the ability of NIH3T3 fibroblast cells to attach to PVA hydrogels was evaluated. Because of PVA's extremely hydrophilic nature, important cell adhesion proteins do not adsorb to PVA hydrogels, and consequently, cells are unable to adhere to the hydrogel. By covalently attaching the important cell adhesion protein fibronectin onto the PVA hydrogel surface, the rate of fibroblast attachment and proliferation was dramatically improved, and promoted two-dimensional cell migration. These studies illustrate that a fibronectin-modified PVA hydrogel is a potential biomaterial for tissue engineering applications.

Charles R. Nuttelman

Papers

Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro

A Versatile Synthetic Extracellular Matrix Mimic via Thiol‐Norbornene Photopolymerization

Synthetic hydrogel niches that promote hMSC viability.

Attachment of fibronectin to poly(vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation, and migration.

Synthesis and characterization of photocrosslinkable, degradable poly(vinyl alcohol)-based tissue engineering scaffolds.