Engineering hydrogels for personalized disease modeling and regenerative medicine

Technological innovations and advances in scientific understanding have created an environment where data can be collected, analyzed, and interpreted at scale, ushering in the era of personalized medicine. The ability to isolate cells from individual patients offers tremendous promise if those cells can be used to generate functional tissue replacements or used in disease modeling to determine optimal treatment strategies. Here, we review recent progress in the use of hydrogels to create artificial cellular microenvironments for personalized tissue engineering and regenerative medicine applications, as well as to develop personalized disease models. We highlight engineering strategies to control stem cell fate through hydrogel design, and the use of hydrogels in combination with organoids, advanced imaging methods, and novel bioprinting techniques to generate functional tissues. We also discuss the use of hydrogels to study molecular mechanisms underlying diseases and to create personalized in vitro disease models to complement existing pre-clinical models. Continued progress in the development of engineered hydrogels, in combination with other emerging technologies, will be essential to realize the immense potential of personalized medicine. STATEMENT OF SIGNIFICANCE: In this review, we cover recent advances in hydrogel engineering strategies with applications in personalized medicine. Specifically, we focus on material systems to expand or control differentiation of patient-derived stem cells, and hydrogels to reprogram somatic cells to pluripotent states. We then review applications of hydrogels in developing personalized engineered tissues. We also highlight the use of hydrogel systems as personalized disease models, focusing on specific examples in fibrosis and cancer, and more broadly on drug screening strategies using patient-derived cells and hydrogels. We believe this review will be a valuable contribution to the Special Issue and the readership of Acta Biomaterialia will appreciate the comprehensive overview of the utility of hydrogels in the developing field of personalized medicine.