Open AccessAdaptable Hydrogels Mediate Cofactor‐Assisted Activation of Biomarker‐Responsive Drug Delivery via Positive Feedback for Enhanced Tissue Regeneration
Author(s) -
Zhang Kunyu,
Jia Zhaofeng,
Yang Boguang,
Feng Qian,
Xu Xiao,
Yuan Weihao,
Li Xingfu,
Chen Xiaoyu,
Duan Li,
Wang Daping,
Bian Liming
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201800875
Subject(s) - self healing hydrogels , regeneration (biology) , dephosphorylation , chemistry , hyaluronic acid , drug delivery , alkaline phosphatase , biophysics , materials science , nanotechnology , microbiology and biotechnology , biochemistry , phosphatase , enzyme , polymer chemistry , organic chemistry , anatomy , medicine , biology
The targeted and simultaneous delivery of diverse cargoes with vastly different properties by the same vehicle is highly appealing but challenging. Here, a bioactive nanocomposite hydrogel based on hyaluronic acid and self‐assembled pamidronate‐magnesium nanoparticles for the localized elution and on‐demand simultaneous release of bioactive ions and small molecule drugs is described. The obtained nanocomposite hydrogels exhibit excellent injectability and efficient stress relaxation, thereby allowing easy injection and consequent adaptation of hydrogels to bone defects with irregular shapes. Magnesium ions released from the hydrogels promote osteogenic differentiation of the encapsulated human mesenchymal stem cells (hMSCs) and activation of alkaline phosphatase (ALP). The activated ALP subsequently catalyzes the dephosphorylation (activation) of Dex phosphate, a pro‐drug of Dex, and expedites the release of Dex from hydrogels to further promote hMSC osteogenesis. This positive feedback circuit governing the activation and release of Dex significantly enhances bone regeneration at the hydrogel implantation sites. The findings suggest that these injectable nanocomposite hydrogels mediate optimized release of diverse therapeutic cargoes and effectively promote in situ bone regeneration via minimally invasive procedures.