Enhanced Osteogenesis of Mesenchymal Stem Cells Encapsulated in Injectable Microporous Hydrogel

TL;DR

This study shows that an injectable microporous hydrogel improves bone formation by human stem cells compared to a nonporous hydrogel.

Contribution

The novel contribution is the development of a microporous hydrogel that enhances stem cell osteogenesis for bone repair.

Findings

MSCs in microporous hydrogel spread rapidly and formed cell-cell connections.

Microporous hydrogel promoted stronger osteogenic differentiation and calcium deposition.

RNA-seq revealed upregulated genes related to cell spreading and osteogenesis in the microporous hydrogel.

Abstract

Delivery of therapeutic stem cells to treat bone tissue damage is a promising strategy that faces many hurdles to clinical translation. Among them is the design of a delivery vehicle which promotes desired cell behavior for new bone formation. In this work, we describe the use of an injectable microporous hydrogel, made of crosslinked gelatin microgels, for the encapsulation and delivery of human mesenchymal stem cells (MSCs) and compared it to a traditional nonporous injectable hydrogel. MSCs encapsulated in the microporous hydrogel showed rapid cell spreading with direct cell-cell connections whereas the MSCs in the nonporous hydrogel were entrapped by the surrounding polymer mesh and isolated from each other. Microporous hydrogel induced more robust osteogenic differentiation of MSCs and calcium mineral deposition than the nonporous hydrogel confirmed by alkaline phosphatase (ALP) assay and calcium assay. RNA-seq confirmed the upregulation of the genes and pathways that are associated with cell spreading and cell-cell connections, as well as the osteogenesis in the microporous hydrogel. These results demonstrate that the microgel-based injectable hydrogels can be useful tools for therapeutic cell delivery for bone tissue repair.