Christopher N. Bowman

Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis

The merits of thiol-click chemistry and its potential for making new forays into chemical synthesis and materials applications are described. Since thiols react to high yields under benign conditions with a vast range of chemical species, their utility extends to a large number of applications in the chemical, biological, physical, materials and engineering fields. This critical review provides insight into emerging venues for application as well as new mechanistic understanding of this exceptional chemistry in its many forms (81 references).

Mechanical properties of hydrogels and their experimental determination

SUMMARY ia The prediction and control of mechanical properties in hydrogels is of great importance in assessing the applicability of hydrogels. In this work we have shown that the mechanical properties are highly dependent on the polymer structure, especially the cross-linking density and the degree of swelling. Methods for measuring the elastic and viscoelastic properties of hydrogels were presented along with mechanisms for controlling the properties. Through variations in the polymer composition, the cross-linking density, and the polymerization conditions, it is remarkably facile to control the mechanical properties of hydrogels. REFERENCES 1 2 3 4 5 6 7 a 9 10 11 12 13 14 15 16 17 19 20 21 Aklonis JJ, MacKnight WJ. Introduction to Polymer Viscoelasficify. New York: Wiley-Interscience, 1983. Ward IM, Hadley PW. An Introduction to the Mechanical Properties of Solid Polymers. New York: Wiley,

In situ forming degradable networks and their application in tissue engineering and drug delivery

Multifunctional macromers based on poly(ethylene glycol) and poly(vinyl alcohol) were photopolymerized to form degradable hydrogel networks. The degradation behavior of the highly swollen gels was characterized by monitoring changes in their mass loss, degree of swelling, and compressive modulus. Experimental results show that the modulus decreases exponentially with time, while the volumetric swelling ratio increases exponentially. A degradation mechanism assuming pseudo first-order hydrolysis kinetics and accounting for the structure of the crosslinked networks successfully predicted the experimentally observed trends in these properties with degradation. Once verified, the proposed degradation mechanism was extended to correlate network degradation kinetics, and subsequent changes in network structure, with release behavior of bioactive molecules from these dynamic systems. A theoretical model utilizing a statistical approach to predict the cleavage of crosslinks within the network was used to predict the complex erosion profiles produced by these hydrogels. Finally, the application of these macromers as in situ forming hydrogel constructs for cartilage tissue engineering is demonstrated.

Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility

Due to mild reaction conditions and temporal and spatial control over material formation, photopolymerization has become a valuable technique for the encapsulation of living cells in three dimensional, hydrated, biomimetic materials. For such applications, 2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone (I2959) is the most commonly used photoinitiator (by virtue of its moderate water solubility), yet this initiator has an absorption spectrum that is poorly matched with wavelengths of light generally regarded as benign to living cells, limiting the rate at which it may initiate polymerization in their presence. In contrast, acylphosphine oxide photoinitiators, generally exhibit absorption spectra at wavelengths suitable for cell encapsulation, yet commercially available initiators of this class have low water solubility. Here, a water soluble lithium acylphosphinate salt is evaluated for its ability to polymerize diacrylated poly(ethylene glycol) (PEGDA) monomers rapidly into hydrogels, while maintaining high viability during direct encapsulation of cells. Through rheometric measurements, the time to reach gelation of a PEGDA solution with the phosphinate initiator is one tenth the time for that using I2959 at similar concentrations, when exposed to 365 nm light. Further, polymerization with the phosphinate initiator at 405 nm visible light exposure is achieved with low initiator concentrations and light intensities, precluded in polymerizations initiated with I2959 by its absorbance profile. When examined 24h after encapsulation, survival rates of human neonatal fibroblasts encapsulated in hydrogels polymerized with the phosphinate initiator exceed 95%, demonstrating the cytocompatibility of this initiating system.

A Versatile Synthetic Extracellular Matrix Mimic via Thiol‐Norbornene Photopolymerization

Step-growth, radically mediated thiol-norbornene photopolymerization is used to create versatile, stimuli-responsive poly(ethylene glycol)-co-peptide hydrogels The reaction is cytocompatible and allows for the encapsulation of human mesenchymal stem cells with a viability greater than 95%. Cellular spreading is dictated via three-dimensional biochemical photopatterning.

Recent Advances and Developments in Composite Dental Restorative Materials

Composite dental restorations represent a unique class of biomaterials with severe restrictions on biocompatibility, curing behavior, esthetics, and ultimate material properties. These materials are presently limited by shrinkage and polymerization-induced shrinkage stress, limited toughness, the presence of unreacted monomer that remains following the polymerization, and several other factors. Fortunately, these materials have been the focus of a great deal of research in recent years with the goal of improving restoration performance by changing the initiation system, monomers, and fillers and their coupling agents, and by developing novel polymerization strategies. Here, we review the general characteristics of the polymerization reaction and recent approaches that have been taken to improve composite restorative performance.

Thiol-yne click chemistry: A powerful and versatile methodology for materials synthesis

Radical mediated thiol-yne polymerization reactions complement the more well-known thiol-ene radical polymerization processes, with the added advantage of increased functionality. In one system studied, the rate constant for the addition of the thiol to the vinyl sulfide created by the initial reaction of the thiol with the alkyne is three times faster than the initial reaction. When hydrocarbon based dialkynes and dithiols were copolymerized, the resulting thiol-alkyne networks containing only hydrocarbon and sulfide linking groups exhibited refractive index values tunable above 1.65, with the refractive index directly related to the sulfur content. The thiol-yne reaction was also found to be useful in functionalizing thiol-terminated polymer chain ends via sequential Michael thiol-ene addition followed by the thiol-yne reaction: the result is the dual functionalization of the polymer chain end. A thermally responsive polymer hydrogel network was formed when an yne terminated water-soluble homopolymer was polymerized with a tetrafunctional thiol.

Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel

The degradation behavior of highly swollen, chemically cross-linked hydrogels was characterized by monitoring changes in their mass loss, degree of swelling and compressive modulus. The hydrogels were used as model systems to investigate the hydrolytic degradation process in cross-linked networks. The trends of the three measured properties differ substantially from those seen for linear degradable systems; however, they can still be predicted accurately using hydrolysis kinetics and network structure. Experimental results show that the modulus decreases exponentially with time while the volumetric swelling ratios for these gels increase exponentially. The characteristic exponential time constants for these two functions, as well as the overall degradation timescale, are influenced greatly by the network structure. Thermodynamic relationships are used to explain these trends as well as relating the observed tradeoff between the two desirable properties of mechanical strength and water content.

Mechanical Properties of Cellularly Responsive Hydrogels and Their Experimental Determination

Hydrogels are increasingly employed as multidimensional cell culture platforms often with a necessity that they respond to or control the cellular environment. Specifically, synthetic hydrogels, such as poly(ethylene glycol) (PEG)-based gels, are frequently utilized for probing the microenvironments influence on cell function, as the gel properties can be precisely controlled in space and time. Synthetically tunable parameters, such as monomer structure and concentration, facilitate initial gel property control, while incorporation of responsive degradable units enables cell- and/or user-directed degradation. Such responsive gel systems are complex with dynamic changes occurring over multiple time-scales, and cells encapsulated in these synthetic hydrogels often experience and dictate local property changes profoundly different from those in the bulk material. Consequently, advances in bulk and local measurement techniques are needed to monitor property evolution quantatively and understand its effect on cell function. Here, recent progress in cell-responsive PEG hydrogel synthesis and mechanical property characterization is reviewed.

The Effects of Light Intensity, Temperature, and Comonomer Composition on the Polymerization Behavior of Dimethacrylate Dental Resins

One of the most common combinations for the organic phase of dental restorative materials is BisGMA (2,2 bis[4-(2-hydroxy-3-methacryloyloxypropoxy) phenylJpropane) and TEGDMA (triethylene glycol dimethacrylate). However, this copolymer has some drawbacks, such as volume shrinkage during cure and lack of complete double-bond conversion. If the properties of this system are to be improved, an attempt must be made to understand the underlying kinetics of the reaction. This work examines the effects of light intensity, temperature, and composition on the polymerization behavior of BisGMA/TEGDMA copolymerizations. Using differential scanning calorimetry, we monitored the rates of photopolymerization for various experimental conditions. The BisGMA/TEGDMA copolymerization behaved similarly to other dimethacrylate systems and exhibited diffusion-controlled kinetics. It was found that the maximum rate of polymerization was significantly affected by the intensity of the light, and the temperature of the polymerization affected the conversion at which the maximum rate occurred. When the composition of the mixture was varied, it was discovered that the viscosity of the system played a significant role in the polymerization rate and the onset of reaction-diffusion-controlled termination. Mixtures which contained from 50 wt% to 75 wt% BisGMA displayed the highest maximum rate. This feature suggests that TEGDMA is an excellent diluent, since it increases the mobility of the reacting medium; however, the high reactivity is due to the presence of BisGMA. Therefore, based on compositional dependence, we conclude that the BisGMA portion of the mixture largely controls the polymerization mechanisms and kinetics.