Arthritis-attributable medical expenditures and earnings losses in the United States were recently estimated to be >$300 billion annually.  This financial burden falls disproportionately on ~8 million people who suffer advanced symptomatic osteoarthritis in load-bearing joints.  Fortunately, tissue engineering strategies such as matrix-assisted autologous chondrocyte transplantation (MACT) have emerged to address the limitations of traditional treatment options, potentially offering low cost and non-invasive cartilage regeneration.
Covalently crosslinked hydrogels are attractive scaffolds for cartilage regeneration because they provide robust mechanical support for chondrocytes in articulating joints. However, these materials typically demonstrate purely elastic responses to deformation despite the dynamic viscoelastic properties of native tissue. I am interested in using dynamic covalent chemistries to develop viscoelastic materials for cartilage tissue engineering. To this end, I use imine crosslink equilibria to form covalent adaptable networks (CANs). By tuning the identity of adjacent chemical moieties and altering the connectivity of network architectures, I study how crosslink adaptation can influence the development of cartilage neotissue in vitro.
Figure 1. Equilibrium reactions of hydrazine with alkyl (a) and benzyl (b) aldehyde forming different hydrazone (Hz) bonds to test chondrocyte response to distinct levels covalent architecture adaptatation. To the right, histological sections show the spatial distribution of collagen deposited by chondrocytes in hydrazone crosslinked poly(ethylene glycol) hydrogels after 28 days of cell culture. The total collagen content as a function of time is show with significance representing 2-way ANOVA with Dunnett's multiple comparison test (n=4), w.r.t 100% bHz P < 0.05 = *, P < 0.01 = **, P < 0.001 = ***, P < 0.0001 = **** and w.r.t day 1 P < 0.05 = +, P < 0.01 = ++, P < 0.001 = +++, P < 0.0001 = ++++. 
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