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Biomaterials. 2019 Oct;217:119294. doi: 10.1016/j.biomaterials.2019.119294. Epub 2019 Jun 20.

Enzymatically-degradable alginate hydrogels promote cell spreading and in vivo tissue infiltration.

Author information

1
Julius Wolff Institute & Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
2
Julius Wolff Institute & Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, 14476 Potsdam, Germany.
3
School of Engineering and Applied Sciences - Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
4
Julius Wolff Institute & Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
5
Julius Wolff Institute & Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, 14476 Potsdam, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany. Electronic address: amaia.cipitria@mpikg.mpg.de.

Abstract

Enzymatically-degradable materials recapitulate the dynamic and reciprocal interactions between cells and their native microenvironment by allowing cells to actively shape the degradation process. In order to engineer a synthetic 3D environment enabling cells to orchestrate the degradation of the surrounding material, norbornene-modified alginate was crosslinked with two different peptide crosslinkers susceptible to cleavage by matrix metalloproteinases using UV-initiated thiol-ene chemistry. Resulting hydrogels were characterized for their initial mechanical and rheological properties, and their degradation behavior was measured by tracking changes in wet weight upon enzyme incubation. This process was found to be a function of the crosslinker type and enzyme concentration, indicating that degradation kinetics could be controlled and tuned. When mouse embryonic fibroblasts were encapsulated in 3D, cell number remained constant and viability was high in all materials, while cell spreading and extensive filopodia formation was observed only in the degradable gels, not in non-degradable controls. After implanting hydrogels into the backs of C57/Bl6 mice for 8 weeks, histological stainings of recovered gel remnants and surrounding tissue revealed higher tissue and cell infiltration into degradable materials compared to non-degradable controls. This alginate-based material platform with cell-empowered enzymatic degradation could prove useful in diverse tissue engineering contexts, such as regeneration and drug delivery.

KEYWORDS:

Alginate hydrogel; Enzymatic degradation; In vivo hydrogel degradation; In vivo tissue infiltration; Peptide crosslinking; Thiol-ene chemistry

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