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Biomaterials. 2019 Jan;189:1-10. doi: 10.1016/j.biomaterials.2018.10.024. Epub 2018 Oct 22.

Defining hydrogel properties to instruct lineage- and cell-specific mesenchymal differentiation.

Author information

1
Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA.
2
Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA 95817, USA.
3
Department of Surgery, Division of Plastic Surgery, UC Davis Health, Sacramento, CA 95817, USA.
4
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA.
5
Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA; Department of Orthopaedic Surgery, UC Davis Health, Sacramento, CA 95817, USA. Electronic address: jkleach@ucdavis.edu.

Abstract

The maintenance and direction of stem cell lineage after implantation remains challenging for clinical translation. Aggregation and encapsulation into instructive biomaterials after preconditioning can bolster retention of differentiated phenotypes. Since these procedures do not depend on cell type or lineage, we hypothesized we could use a common, tunable platform to engineer formulations that retain and enhance multiple lineages from different cell populations. To test this, we varied alginate stiffness and adhesive ligand content, then encapsulated spheroids of varying cellularity. We used Design-of-Experiments to determine the effect of these parameters and their interactions on phenotype retention. The combination of parameters leading to maximal differentiation varied with lineage and cell type, inducing a 2-4-fold increase over non-optimized levels. Phenotype was also retained for 4 weeks in a murine subcutaneous model. This widely applicable approach can facilitate translation of cell-based therapies by instructing phenotype in situ without prolonged induction or costly growth factors.

KEYWORDS:

Alginate; Design-of-Experiments; Phenotype retention; Spheroid

PMID:
30384124
PMCID:
PMC6237198
[Available on 2020-01-01]
DOI:
10.1016/j.biomaterials.2018.10.024

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