The meniscus is a fibrous tissue with multiple levels of architecture, including a fibrous aligned region which transitions to a less fibrous, more vascularized region. To effectively study this environment, we aim to synthesize scaffolds which can mimic these structures and expose cells to similar mechanical and chemical signals found in the body. To make these fibrous regions, we primarily use electrospinning. This is a technique where a voltage is applied to a polymer solution as it is extruded, which creates a charged jet that whips through the air until contacting a grounded collection target. Other ongoing projects examine how a modified chemistry can be used to create hydrogels with varying mechanical properties to mimic the more vascular and less fibrous regions of the meniscus. 

We have designed a hyaluronic acid-based hydrogel system with tunable mechanical properties. This system involves the functionalization of hyaluronic acid with pentenoic anhydride. This pentenoate-functionalized hyaluronic acid (PHA) has reactive -ene groups along its backbone that participate in a photoinitiated thiol-ene crosslinking reaction using dithiothreitol as the crosslinker. By altering the molar ratio of the reactants in the PHA functionalization reaction, we are able to control degree of -ene group substitution (DoS), which allows control over crosslinking density and, subsequently, the mechanical properties of the hydrogels.

Some ongoing studies with these materials examine variance in response to stiffer or softer hydrogels between male and female cells and similar variances in response or activation of mechanotransduction pathways of male and female cells when cultured on aligned versus unaligned electrospun fibers.
Process of PHA hydrogel fabrication.

 

Selected Publications:

Burkey K, Castillo K, Elrod P, et al. Modulating pentenoate-functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction. J Biomed Mater Res. 2023; 111(10): 1525-1537. DOI: 10.1002/jbm.a.37551 (https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.37551)