Photoselective Delivery of Model Therapeutics from Hydrogels

Griffin, Donald R.; Kasko, Andrea M.

doi:10.1021/mz300366s

Cited by 83 publications

(92 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Azagarsamy et al demonstrated the high level of on/off control that photo-degradable nanoparticles provide [312]. Griffin and Kasko took this work a step further by including multiple therapeutics that released in response to different wavelengths of light [313]. They included three alternatively modified nitrobenzene linkers that connected the drugs into the backbone of the hydrogel.…”

Section: Photo-responsive Hydrogelsmentioning

confidence: 99%

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Koetting

Peters

Steichen

et al. 2015

Materials Science and Engineering: R: Reports

866

688

View full text Add to dashboard Cite

Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry.

show abstract

Section: Photo-responsive Hydrogelsmentioning

confidence: 99%

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Koetting

Peters

Steichen

et al. 2015

Materials Science and Engineering: R: Reports

866

688

View full text Add to dashboard Cite

show abstract

“…Furthermore, each new therapeutic agent of interest would require independent synthesis. We next reported a series of o -NB linkers with different rates of photodegradation to allow the multistaged release of cells 15 and model therapeutics 16 . Although these reports resolved some of the issues noted above, the variety of functional groups that could be incorporated was still limited.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Photodegradable Macromers for Conjugation and Release of Bioactive Molecules

et al. 2013

Self Cite

View full text Add to dashboard Cite

Hydrogel scaffolds are used in biomedicine to study cell differentiation and tissue evolution, where it is critical to control the delivery of chemical cues both spatially and temporally. While large molecules can be physically entrapped in a hydrogel, moderate molecular weight therapeutics must be tethered to the hydrogel network through a labile linkage to allow controlled release. We synthesized and characterized a library of polymerizable ortho-nitrobenzyl (o-NB) macromers with different functionalities at the benzylic position (alcohol, amine, BOC-amine, halide, acrylate, carboxylic acid, activated disulfide, N-hydroxysuccinyl ester, biotin). This library of polymerizable macromers containing o-NB groups should allow direct conjugation of nearly any type of therapeutic agent and its subsequent controlled photorelease from a hydrogel network. As proof-of-concept, we incorporated the N-hydroxysuccinyl ester macromer into hydrogels, and then reacted phenylalanine with the NHS ester. Upon exposure to light (λ=365 nm. 10 mW/cm2, 10 min) 81.3% of the phenylalanine was released from the gel. Utilizing the photodegradable macromer incorporating an activated disulfide, we conjugated a cell-adhesive peptide (GCGYGRGDSPG), a protein that exhibits enzymatic activity (bovine serum albumin (BSA)), and a growth factor (transforming growth factor-β1 (TGF-β1)) into hydrogels, controlled their release with light (λ=365 nm. 10 mW/cm2, 0–20 min), and verified the bioactivity of the photoreleased molecules. The photoreleasable peptide allows real-time control over cell adhesion. BSA maintains full enzymatic activity upon sequestration and release from the hydrogel. Photoreleased TGF-β1 is able to induce chondrogenic differentiation of human mesenchymal stem cells comparable to native TGF-β1. Through this approach, we have demonstrated that photodegradable tethers can be used to sequester peptides and proteins into hydrogel depots and release them in an externally controlled, predictable manner without compromising biological function.

show abstract

“…[11] The o -NB cage prevents the FXIIIa catalyzed attachment of the glutaminyl peptide residue in the Q-peptide. The o-NB cage was chosen for its high absorption spectra (λpeak~350nm) and fast degradation time (t 1/2 ~7–8m at 10 mW/cm 2 ), [11–12] which minimizes the risk of damage to present biomolecules (e.g. DNA).…”

Section: Resultsmentioning

confidence: 99%

“…Using a simplified equation for exponential degradation [14] (equation 1) we determined the intensity dependent degradation constant of the caged K-peptide (k = 0.00024 sec −1 (mW/cm 2 ) −1 ), which is comparable to previously published results of o-NB groups derived from vanillin (k = 0.00015; k = 0.00026). [11–12] At 20 mW/cm 2 , this degradation constant results in a t 1/2 of ~208 s, which can be increased by lowering the light intensity (e.g. 10 mW/cm 2 : t 1/2 = 416 s) or decreased by increasing the light intensity.…”

Section: Resultsmentioning

confidence: 99%

Hybrid Photopatterned Enzymatic Reaction (HyPER) for in Situ Cell Manipulation

et al. 2014

Self Cite

View full text Add to dashboard Cite

The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fate in vitro and to guide tissue repair in vivo. One main component of the design of artificial extracellular matrices is the incorporation of biochemical cues to guide cell phenotype and multicellular organization. The extracellular matrix is composed of a heterogeneous mixture of proteins that present a variety of spatially discrete signals to residing cell populations. In contrast, most engineered ECMs do not mimic this heterogeneity. In recent years the use of photodeprotection has been used to achieve spatial immobilization of signals. However, these approaches have been limited mostly to small peptides. Here we combine photodeprotection with enzymatic reaction to achieve spatially controlled immobilization of active bioactive signals that range from small molecules to large proteins. A peptide substrate for transglutaminase factor XIII (FXIIIa) is caged with a photodeprotectable group, which is then immobilized to the bulk of a cell compatible hydrogel. With the use of focused light the substrate can be deprotected and used to immobilize patterned bioactive signals. This approach offers an innovative strategy to immobilize delicate bioactive signals, such as growth factors, without loss of activity and enables In situ cell manipulation of encapsulated cells.

show abstract

Photoselective Delivery of Model Therapeutics from Hydrogels

Cited by 83 publications

References 28 publications

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Stimulus-responsive hydrogels: Theory, modern advances, and applications

Synthesis of Photodegradable Macromers for Conjugation and Release of Bioactive Molecules

Hybrid Photopatterned Enzymatic Reaction (HyPER) for in Situ Cell Manipulation

Contact Info

Product

Resources

About