Cell biology

Mathematics education

Biotechnology

Polymer chemistry

Biology

Mesenchymal stem cell

Microfluidics

Biomedical engineering

Materials science

Cell encapsulation

Stromal cell

Tissue engineering

Biochemistry

In vivo

Nanotechnology

Self-healing hydrogels

Mathematics

Microscale chemistry

Regenerative medicine

Medicine

Chemistry

Cell

Biophysics

Pathology

Nature Materials

Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel's mechanical properties. Here, we report a microfluidic-based method for encapsulating single cells in an approximately six-micrometre layer of alginate that increases the proportion of cell-containing microgels by a factor of ten, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that, for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.

Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery