Design of Injectable Materials to Improve Stem Cell Transplantation

Abstract

Stem cell-based therapies are steadily gaining traction for regenerative medicine approaches to treating disease and injury throughout the body. While a significant body of work has shown success in preclinical studies, results often fail to translate in clinical settings. One potential cause is the massive transplanted cell death that occurs post injection, preventing functional integration with host tissue. Therefore, current research is focusing on developing injectable hydrogel materials to protect cells during delivery and to stimulate endogenous regeneration through interactions of transplanted cells and host tissue. This review explores the design of targeted injectable hydrogel systems for improving the therapeutic potential of stem cells across a variety of tissue engineering applications with a focus on hydrogel materials that have progressed to the stage of preclinical testing.

Keywords: cell survival; functional recovery; injectable hydrogels; regenerative medicine; stem cells.

Figure 1. Design of injectable hydrogel delivery platforms for improved stem cell-derived therapeutics

A) Combinatorial regenerative medicine strategies often include encapsulation of stem cell-derived transplants within injectable hydrogels designed to provide cell appropriate mechanical support and biochemical cues along with co-encapsulation of bioactive factors. B) The design of injectable hydrogels must consider four separate phases of hydrogel use. In the first and second, some injectable hydrogels can protect cells during the potentially harmful pre-injection and injection processes, which exposes cells to a variety of crosslinking mechanisms and mechanical forces. Third, some injectable hydrogels can improve acute cell survival and functionality by providing appropriate mechanical and biochemical matrix cues along with soluble bioactive factors. Fourth, carefully developed injectable materials can promote grafted cell function within host tissue as it degrades.

Figure 1. Design of injectable hydrogel delivery platforms for improved stem cell-derived therapeutics

A) Combinatorial regenerative medicine strategies often include encapsulation of stem cell-derived transplants within injectable hydrogels designed to provide cell appropriate mechanical support and biochemical cues along with co-encapsulation of bioactive factors. B) The design of injectable hydrogels must consider four separate phases of hydrogel use. In the first and second, some injectable hydrogels can protect cells during the potentially harmful pre-injection and injection processes, which exposes cells to a variety of crosslinking mechanisms and mechanical forces. Third, some injectable hydrogels can improve acute cell survival and functionality by providing appropriate mechanical and biochemical matrix cues along with soluble bioactive factors. Fourth, carefully developed injectable materials can promote grafted cell function within host tissue as it degrades.