Engineering immunomodulatory biomaterials for type 1 diabetes

Abstract

A cure for type 1 diabetes (T1D) would help millions of people worldwide, but remains elusive thus far. Tolerogenic vaccines and beta cell replacement therapy are complementary therapies that seek to address aberrant T1D autoimmune attack and subsequent beta cell loss. However, both approaches require some form of systematic immunosuppression, imparting risks to the patient. Biomaterials-based tools enable localized and targeted immunomodulation, and biomaterial properties can be designed and combined with immunomodulatory agents to locally instruct specific immune responses. In this Review, we discuss immunomodulatory biomaterial platforms for the development of T1D tolerogenic vaccines and beta cell replacement devices. We investigate nano-and microparticles for the delivery of tolerogenic agents and autoantigens, and as artificial antigen presenting cells, and highlight how bulk biomaterials can be used to provide immune tolerance. We examine biomaterials for drug delivery and as immunoisolation devices for cell therapy and islet transplantation, and explore synergies with other fields for the development of new T1D treatment strategies.

Interpenetrating Network of Alginate–Human Adipose Extracellular Matrix Hydrogel for Islet Cells Encapsulation

“…[ 2 ] There are more than 500 000 patients diagnosed with T1DM each year with an annual incidence increment of ≈3% worldwide. [ 3,4 ] Patients with T1DM require lifelong insulin therapy. Currently, insulin administration via subcutaneous insulin injection is the primary mode of treatment.…”

2D and 3D electrospinning technologies for the fabrication of nanofibrous scaffolds for skin tissue engineering: A review

“…To overcome those immunological challenges that are associated with artificial skin grafts derived from autologous cells, allogeneic cells, or xenographic tissues, the patients can receive immunosuppressive treatment (Dixit et al, ). Moreover, immunomodulatory biomaterials (IBMs) can enable localized and targeted immunomodulation to the wound site, promoting specific immune responses, which can prevent the need for immunosuppressive medications, while prolonging the implant's lifetime (Stabler, Li, Stewart, & Keselowsky, ). Common strategies for implementing immunomodulation activity in NFs are the M1/M2 macrophage polarization (Castellano et al, ), glycosaminoglycans (GAGs) (Jiang, Wu, et al, ), and decellularized ECM material (Du et al, ; Gholipourmalekabadi et al, ).…”

Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability

“…Subcutaneous administration would avoid bioavailability issues that plague Rapamune including first pass metabolism, elimination by intestinal cytochrome P450 and p-glycoprotein, and variability associated with food content. Importantly, the subcutaneous route of administration provides the advantage of targeting lymphatic drainage 16 . Unlike intravenous administration, the subcutaneous route allows patients to take their medication from their own home.…”

“…But the subcutaneous route does provide access to antigen presenting cells (APCs), including the aforementioned DCs that can elicit potent tolerogenic responses upon modulation by rapamycin. Tolerogenic DCs (tDCs) constitutively generate regulatory T cells (Tregs) as well as express anti-inflammatory cytokines, both of which have been linked to enhanced survival of transplanted islets 16 .…”