Protein-based microneedles for biomedical applications: A systematic review

Microneedles are minimally-invasive devices with the unique capability of bypassing physiological barriers. Hence, they are widely used for different applications from drug/vaccine delivery to diagnosis and cosmetic fields. Recently, natural biopolymers (particularly carbohydrates and proteins) have garnered attention as safe and biocompatible materials with tailorable features for microneedle construction. Several review articles have dealt with carbohydrate-based microneedles. This review aims to highlight the less-noticed role of proteins through a systematic search strategy based on the PRISMA guideline from international databases of PubMed, Science Direct, Scopus, and Google Scholar. Original English articles with the keyword "microneedle(s)" in their titles along with at least one of the keywords "biopolymers, silk, gelatin, collagen, zein, keratin, fish-scale, mussel, and suckerin" were collected and those in which the proteins undertook a structural role were screened. Then, we focused on the structures and applications of protein-based microneedles. Also, the unique features of some protein biopolymers that make them ideal for microneedle construction (e.g., excellent mechanical strength, self-adhesion, and self-assembly), as well as the challenges associated with them were reviewed. Altogether, the proteins identified so far seem not only promising for the fabrication of "better" microneedles in the future but also inspiring for designing biomimetic structural biopolymers with ideal characteristics.