RT Journal Article
T1 Cardiac extracellular matrix hydrogel enriched with polyethylene glycol presents improved gelation time and increased on-target site retention of extracellular vesicles
A1 Gomez Cid, Lidia
A1 López-Donaire, María Luisa
A1 Velasco Bayón, Diego
A1 Marín Calahorrano, Víctor-Jesús
A1 González, María Isabel
A1 Salinas Rodríguez, Beatriz
A1 Cusso Mula, Lorena
A1 García, Ángel
A1 Bravo, Susana Belén
A1 Fernández-Santos, María Eugenia
A1 Elvira, Carlos
A1 Sierra, Johanna
A1 Arroba, Ester
A1 Bañares, Rafael
A1 Grigorian-Shamagian, Lilian
A1 Fernández-Avilés, Francisco
AB Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs–PEG–cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs–PEG–cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.
PB MDPI
SN 1422-0067
YR 2021
FD 2021-09-01
LK https://hdl.handle.net/10016/33348
UL https://hdl.handle.net/10016/33348
LA eng
NO This article belongs to the Special Issue Extracellular Matrix in Development and Disease 3.0
NO This study was supported by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain. PI16/01123; PI19/00161; Red de Terapia Celular (RD16.0011.0029) and CIBERCV (CB16.11.00292). It has also been partially supported by Comunidad de Madrid, projects S2017/BMD-3867 and EXOHEP-CM S2017/BMD-3727, co-funded by European Structural and Investment Fund, FSE, to RB and by Instituto de Salud Carlos III through the project PT20/00044, co-funded by European Regional Development Fund "A way to make Europe".
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