4.8 Article

A modular, injectable, non-covalently assembled hydrogel system features widescale tunable degradability for controlled release and tissue integration

Journal

BIOMATERIALS
Volume 269, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.120637

Keywords

Biocompatibility; MMP-cleavable peptide; Modular building blocks; Small animal imaging; Sulphated hyaluronic acid

Funding

  1. Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center [Transregio 67, CRC/TRR 67/3]
  2. Helmholtz Association through the Helmholtz Cross-Programme Initiative Technology and Medicine - Adaptive Systems
  3. China Scholarship Council
  4. German Federal Ministry of Research and Education (BMBF) [03Z2EN12, 03Z2E511]

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This study presents an injectable hydrogel system based on oligopeptides interacting with sulphated polysaccharides, showing high tolerability and biocompatibility in mice. The degradation rate of the hydrogels can be varied by altering components, allowing for sustained release of growth factors.
Biomaterials with attenuated adverse host tissue reactions, and meanwhile, combining biocompatibility with mimicry of mechanical and biochemical cues of native extracellular matrices (ECM) to promote integration and regeneration of tissues are important for many biomedical applications. Further, the materials should also be tailorable to feature desired application-related functions, like tunable degradability, injectability, or controlled release of bioactive molecules. Herein, a non-covalently assembled, injectable hydrogel system based on oligopeptides interacting with sulphated polysaccharides is reported, showing high tolerability and biocompatibility in immunocompetent hairless mice. Altering the peptide or polysaccharide component considerably varies the in vivo degradation rate of the hydrogels, ranging from a half-life of three weeks to no detectable degradation after three months. The hydrogel with sulphated low molecular weight hyaluronic acid exhibits sustained degradation-mediated release of heparin-binding molecules in vivo, as shown by small animal magnetic resonance imaging and fluorescence imaging, and enhances the expression of vascular endothelial growth factor in hydrogel surrounding. In vitro investigations indicate that M2-macrophages could be responsible for the moderate difference in pro-angiogenic effects. The ECM-mimetic and injectable hydrogels represent tunable bioactive scaffolds for tissue engineering, also enabling controlled release of heparin-binding signalling molecules including many growth factors.

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