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Cell therapy has already had an important impact on healthcare and provided new treatments for previously intractable diseases. Notable examples include mesenchymal stem cells for tissue regeneration, islet transplantation for diabetes treatment, and T cell delivery for cancer immunotherapy. Biomaterials have the potential to extend the therapeutic impact of cell therapies by serving as carriers that provide 3D organization and support cell viability and function. With the growing emphasis on personalized medicine, cell therapies hold great potential for their ability to sense and respond to the biology of an individual patient. These therapies can be further personalized through the use of patient-specific cells or with precision biomaterials to guide cellular activity in response to the needs of each patient. Here, the role of biomaterials for applications in tissue regeneration, therapeutic protein delivery, and cancer immunotherapy is reviewed, with a focus on progress in engineering material properties and functionalities for personalized cell therapies., Juvenile Diabetes Research Foundation (Grant 2-SRA-2019-714-S-B), Leona M. and Harry B. Helmsley Charitable Trust (Grant 2017PG-T1D027)

An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days., National Cancer Institute (Grant P30-CA14051)