PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon...

Marrow stromal cells (MSCs) have been suggested as a means to improve healing in tendon overuse injuries (tendinopathy), but optimal delivery methods for these cells have yet to be determined. In this study novel degradable hydrogels based on oligo(poly(ethylene glycol) fumarate) (OPF) and acrylated poly(ethylene glycol)-dithiothreitol (Ac PEG-DTT) with tunable degradation times ranging from a few days to >1 month were synthesized as MSC carriers for tendon overuse injuries. The addition of higher amounts of OPF or higher dithiothreitol (DTT) concentrations resulted in enhanced fold swelling and degradation. Three formulations, including non-degrading, slower degrading (degraded in ∼10 days) and faster degrading (degraded in ∼5 days) hydrogels were selected for studies with MSCs in tendon tissue explants that had been treated with collagenase as a reproducible model of tendinopathy. Quantitative analysis of the resulting histology images indicated that cell delivery from the hydrogels was dependent on the degradation rate, with cells present in the tissue only after hydrogel dissolution. In addition, significantly more cells were found in the tendon after 14 days with the fast degrading (53±19) vs. slow degrading (20±6) hydrogels. Based on these results, OPF/Ac PEG-DTT hydrogels provide a versatile biomaterial platform to control cell delivery and thus better identify dosing regimens required for MSC-based therapies for tendinopathy.