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Published in Journal of Controlled Release: Injectable starPEG–heparin hydrogels deliver mesenchymal stromal cell secretome for two weeks of sustained immunomodulation
Maria Rossello-Gelabert, Lucas Schirmer and co-workers report an injectable starPEG–heparin hydrogel that stabilises a lyophilised, immunomodulatory secretome of mesenchymal stromal cells (MSCs) and releases its bioactive factors over 14 days.
The MSC secretome is a promising cell-free therapeutic, but its clinical use is limited by the poor stability and short half-life of its cytokines and growth factors, which usually requires repeated administration. In the hydrogel, the heparin building block binds and protects secretome components, while matrix-metalloproteinase-cleavable peptide crosslinks allow the network to be remodelled – in this case by proteases contained in the secretome itself. The interplay of affinity-based retention and enzyme-responsive degradation yielded a sustained and compositionally balanced release of regenerative and immunomodulatory factors including VEGF, PDGF-AA/BB, IL-1Ra, IL-4, IL-10, Gal-9 and TIMP-1.
The released secretome retained its bioactivity throughout the two-week period: it suppressed the proliferation of stimulated peripheral blood mononuclear cells and partially repolarised pro-inflammatory M1 macrophages towards an anti-inflammatory phenotype. The platform therefore addresses a central bottleneck of cell-free MSC-based therapies and offers a tunable matrix for delivering complex paracrine formulations over clinically meaningful timescales.
The work was carried out together with the NanoBioCel Research Group at the University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
The article can be accessed at https://doi.org/10.1016/j.jconrel.2026.115196
04.08.2026