Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) have great therapeutic potential for tissue engineering and regenerative medicine due to their multipotency and paracrine functions. However, shortly after in vivo implantation, MSCs tend to migrate to the lungs and undergo apoptosis, which impairs their clinical efficacy. In addition, the ex vivo two-dimensional expansion of MSCs results in changes in their immunophenotype and functional activities compared to those in vivo. The use of biomaterials to culture and deliver MSCs has the potential to overcome these limitations. MSC-biomaterial constructs retain MSCs in situ and prolong their survival, while the MSCs ameliorate the foreign body reaction and fibrosis caused by the biomaterial. Biomaterial scaffolds can both preserve the tissue architecture and provide a three-dimensional biomimetic milieu for embedded MSCs, which enhance their paracrine functions, including their immunomodulatory potential. The dimensionality, physical characteristics, topographical cues, biochemistry, and microstructure can enhance the immunomodulatory potential of MSCs. Here, we review the link between the properties of biomaterial and the immunomodulatory potential of MSCs. Impact Statement Regeneration of cells, tissues, and whole organs is challenging. Mesenchymal stem cells (MSCs) have therapeutic potential in tissue engineering and regenerative medicine due to their paracrine functions, including immunomodulatory activity. The dimensionality, physical characteristics, topographical cues, biochemistry, and microstructure of biomaterial can be harnessed to enhance the immunomodulatory potential of MSCs for tissue engineering, which will increase their clinical efficacy, particularly for immune-related diseases.