In this paper, Tobin Brown and I developed and characterized a synthetically tractable photodegradable hydrogel and demonstrated the ability to control the extension of motor axons. Check it out at http://pubs.acs.org/doi/abs/10.1021/bm500731b. The abstract appears below:
Hydrogels with photocleavable units incorporated into the cross-links have provided researchers with the ability to control mechanical properties temporally and study the role of matrix signaling on stem cell function and fate. With a growing interest in dynamically tunable cell culture systems, methods to synthesize photolabile hydrogels from simple precursors would facilitate broader accessibility. Here, a step-growth photodegradable poly(ethylene glycol) (PEG) hydrogel system cross-linked through a strain promoted alkyne–azide cycloaddition (SPAAC) reaction and degraded through the cleavage of a nitrobenzyl ether moiety integrated into the cross-links is developed from commercially available precursors in three straightforward synthetic steps with high yields (>95%). The network evolution and degradation properties are characterized in response to one- and two-photon irradiation. The PEG hydrogel is employed to encapsulate embryonic stem cell-derived motor neurons (ESMNs), and in situ degradation is exploited to gain three-dimensional control over the extension of motor axons using two-photon infrared light. Finally, ESMNs and their in vivo synaptic partners, myotubes, are coencapsulated, and the formation of user-directed neural networks is demonstrated.
My ACS Macro Letters paper where I, along with Malar Azagarsamy, characterized the gelation and degradation behavior of a PEG hydrogel containing a photodegradable coumarin moiety in the crosslinker. We found the coumarin molecule enables extremely rapid degradation at both visible and ultraviolet wavelengths behaves very nicely in accordance with established theories. Have a read at http://pubs.acs.org/doi/abs/10.1021/mz500230p. The abstract is pasted below:
The design, synthesis, and characterization of a new class of coumarin-based photodegradable hydrogels are reported. Hydrogel formation was achieved rapidly and efficiently under aqueous conditions using copper-catalyzed click chemistry, which afforded excellent control over the rate of network formation. Rapid photodegradation, to the point of reverse gelation, was observed using both 365 and 405 nm light, and micrometer-scale features were eroded using two-photon irradiation at wavelengths as long as 860 nm.
On May 2nd, I successfully defended my thesis in front of my committee consisting of Kristi Anseth, my advisor, Stephanie Bryant, Jen Cha, Curt Freed, and Joel Kaar. They were very satisfied with my doctoral work and I ended up with no revisions, although I will still be submitting two papers. A week later, I walked with my class, in which twelve Chemical Engineering PhDs were awarded. Here we all are after the ceremony.
After several hard months of work, my PhD thesis is complete and in the hands of my committee members. 222 pages of pure knowledge (that must be a lucky number)! I look forward to defending May 2 and immediately beginning work full time with Agribotix (www.agribotix.com) to ensure our first customers are satisfied this summer.
Less than a week ago I have my last talk as a graduate student to a very receptive audience at the Society for Biomaterials Spring meeting in Denver. My talk, entitled “Cytocompatible Covalently Adaptable Networks to Probe Biophysical Behavior of Encapsulated Cells” detailed the work I’ve done developing the bis-aliphatic hydrazone crosslinked gel and it’s applications in biomaterials. I look forward to submitting another paper or two on the subject and then defending my thesis and moving on to the next.
My article, written with Dylan Domaille, appears in Chemistry of Materials. Check it out here: http://pubs.acs.org/doi/abs/10.1021/cm5007789. We demonstrated predictable control of the material properties of the hydrazone crosslinked hydrogel by varying bath pH. The abstract is below:
Rheological and small molecule kinetic studies were performed to study the formation and hydrolysis of the bis-aliphatic hydrazone bond. The rate of gelation was found to correspond closely with the rate of bond formation and the rate of gel relaxation with the rate of hydrolysis, indicating that small molecule kinetic studies can play an important role in material design. Furthermore, unlike aryl or acyl hydrazone bonds, the bis-aliphatic hydrazone bond forms rapidly under physiological conditions without requiring aniline catalysis yet maintains a pH-dependent rate of hydrolysis. These results suggest the bis-aliphatic hydrazone bond should find use alongside existing bioorthogonal click chemistries for bioconjugation, biomaterial synthesis, and controlled release applications.
I was pleasantly surprised to see that the abstract I submitted to the 2014 Society of Biomaterials meeting was recognized with a STAR (Student Travel Achievement Recognition) Award by the Education and Professional Development Committee of the Society. As an awardee, I get $250, a certificate I can hang on my fridge, and a star next to my name in the abstract booklet so more people will show up. My talk will be at 9:45 am on Thursday, April 17th and is entitled “Cytocompatible Covalently Adaptable Networks to Probe Biophysical Behavior of Encapsulated Cells.” Please show up and say hi if you’re planning on attending the conference.
After a lot of hard work and preparation, Agribotix came to the Cleantech Finals of the University of Colorado New Venture Challenge ready to compete. Seven other excellent teams were invited, but thanks invaluable feedback from our mentors we were able to win the overall prize of $2,500 and an invitation to compete for the overall best business in April. The judges gave us outstanding feedback and we look forward to the next round. Check out our website at www.agribotix.com.
From left to right: Tom McKinnon, Paul Hoff, Wayne Greenberg, me, Phil Calabrese, and Steve Berens, one of our judges
My Advanced Materials paper, describing the synthesis and application of a step-growth PEG hydrogel crosslinked by hydrazone bonds, was awarded the front cover of issue Volume 26, Issue 6. Michael Brasino, a colleague in the Cha Lab, designed the cover for us in Maya, trying to show a cell pushing through the hydrogel. I think it looks great and I’m thrilled that a prestigious journal is recognizing our work through a front cover. Check it out at http://onlinelibrary.wiley.com/doi/10.1002/adma.201470033/abstract.
My first paper, published in Biomaterials Science, was one of 2013′s most-accessed papers. In that work, I showed a synthetic niche capable of supported the viability and axon extension of embryonic stem cell-derived motor neurons and demonstrated the importance of matrix biochemical functionalization and mechanics. The full list can be seen at http://pubs.rsc.org/en/journals/articlecollectionlanding?sercode=bm&themeid=993f9821-cb39-4208-91fe-b41c0fc25970.