Abstract
Biomaterials hold great promise for vaccines and immunotherapy. One emerging biomaterials technology is microneedle (MNs) delivery. MNs are arrays of micrometer-sized needles that are painless and efficiently deliver cargo to the specialized immunological niche of the skin. MNs typically do not require cold storage and eliminate medical sharps. Nearly all materials exhibit intrinsic properties that can bias immune responses toward either pro-immune or inhibitory effects. Thus, because MNs are fabricated from degradable polymers to enable cargo loading and release, understanding the immunological profiles of these matrices is essential to enable new MN vaccines and immunotherapies. Additionally, understanding the mechanical properties is important because MNs must penetrate the skin and conform to a variety of skin or tissue geometries. Here we fabricated MNs from important polymer classes – including extracellular matrix biopolymers, naturally-derived polymers, and synthetic polymers – with both high- and low-molecular-weights (MW). We then characterized the mechanical properties and intrinsic immunological properties of these designs. The library of polymer MNs exhibited diverse mechanical properties, while causing only modest changes in innate signaling and antigen-specific T cell proliferation. These data help inform the selection of MN substrates based on the mechanical and immunological requirements needed for a specific vaccine or immunotherapy application.
Highlights
Existing pathogens and diseases continue to create challenges for current vaccine and immunotherapy technologies
We began by assessing polymers with three different origins 1) those derived from the extracellular matrix - gelatin and hyaluronic acid (HA), 2) naturally-derived polymers carboxymethyl cellulose (CMC) and dextran, and 3) synthetic polymers - polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP)
Most matrices exhibited fracture forces greater than 4N (Figure 2B), the minimum force required to penetrate the skin for these geometries [24]
Summary
Existing pathogens and diseases continue to create challenges for current vaccine and immunotherapy technologies. The challenges span efficacy and selectivity, and distribution, storage, and compliance [1, 2]. For example, the COVID-19 pandemic highlights the need for vaccines that can be disseminated without the need for refrigeration or complex cold chains [3]. Evident is the need for vaccines that generate potent and durable responses [4]. In cancer immunotherapy – where the target antigens are on Intrinsic Immunogenicity of Polymeric Microneedles cancerous host cells or tissues, there is a great need for safe and selective approaches that generate strong responses against difficult-to-detect tumor antigens. Integrating new engineering technologies to improve the distribution, storage, and performance characteristics of vaccines and immunotherapies could enable next-generation vaccines that are deployed and generate strong and selective outcomes
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