Fibrous materials have garnered much interest in the field of biomedical engineering due to their high surface-area-to-volume ratio, porosity, and tunability. Specifically, in the field of tissue engineering, fiber meshes have been used to create biomimetic nanostructures that allow for cell attachment, migration, and proliferation, to promote tissue regeneration and wound healing, as well as controllable drug delivery. In addition to the properties of conventional, synthetic polymer fibers, fibers made from natural polymers, such as proteins, can exhibit enhanced biocompatibility, bioactivity, and biodegradability. Of these proteins, keratin, collagen, silk, elastin, zein, and soy are some the most common used in fiber fabrication. The specific capabilities of these materials have been shown to vary based on their physical properties, as well as their fabrication method. To date, such fabrication methods include electrospinning, wet/dry jet spinning, dry spinning, centrifugal spinning, solution blowing, self-assembly, phase separation, and drawing. This review serves to provide a basic knowledge of these commonly utilized proteins and methods, as well as the fabricated fibers’ applications in biomedical research.

The mussel byssus has long been a source of inspiration for the adhesion community. Recently, adhesive synergy between flanking lysine (Lys, K) and 3,4-Dihydroxyphenylalanine (DOPA, Y) residues in the mussel foot proteins (Mfps) has been highlighted. However, the complex topological relationship of DOPA and Lys as well as the interfacial adhesive roles of other amino acids have been understudied. Herein, we study adhesion of Lys and DOPAcontaining peptides to organic and inorganic substrates using single-molecule force spectroscopy (SMFS). We show that a modest increase in peptide length, from KY to (KY) 3 , increases adhesion strength to TiO 2. Surprisingly, further increase in peptide length offers no additional benefit. Additionally, comparison of adhesion of dipeptides containing Lys and either DOPA (KY) or phenylalanine (KF) shows that DOPA is stronger and more versatile. We furthermore demonstrate that incorporating a nonadhesive spacer between (KY) repeats can mimic the hidden length in the Mfp and act as an effective strategy to dissipate energy.

Nanoparticles are particles that range in size from about 1–1000 nanometers in diameter, about one thousand times smaller than the average cell in a human body. Their small size, flexible fabrication, and high surface-area-to-volume ratio make them ideal systems for drug delivery. Nanoparticles can be made from a variety of materials including metals, polysaccharides, and proteins. Biological protein-based nanoparticles such as silk, keratin, collagen, elastin, corn zein, and soy protein-based nanoparticles are advantageous in having biodegradability, bioavailability, and relatively low cost. Many protein nanoparticles are easy to process and can be modified to achieve desired specifications such as size, morphology, and weight. Protein nanoparticles are used in a variety of settings and are replacing many materials that are not biocompatible and have a negative impact on the environment. Here we attempt to review the literature pertaining to protein-based nanoparticles with a focus on their application in drug delivery and biomedical fields. Additional detail on governing nanoparticle parameters, specific protein nanoparticle applications, and fabrication methods are also provided.

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Deformability of injectable nanocarriers impacts rheological behavior, drug loading, and affinity target adhesion. Here, we present atomic force microscopy (AFM) and spectroscopy measurements of nanocarrier Young’s moduli, tune the moduli of deformable nanocarriers with cross-linkers, and demonstrate vascular targeting behavior that correlates with Young’s modulus. Homobifunctional cross-linkers were introduced into lysozyme-dextran nanogels (NGs). Single particle-scale AFM measurements determined NG moduli varying from ∼50–150 kPa for unmodified NGs or NGs with a short hydrophilic cross-linker (2,2′-(ethylenedioxy)­bis­(ethylamine), EOD) to ∼350 kPa for NGs modified with a longer hydrophilic cross-linker (4,9-dioxa-1,12-dodecanediamine, DODD) to ∼10 MPa for NGs modified with a longer hydrophobic cross-linker (1,12-diaminododecane, DAD). Cross-linked NGs were conjugated to antibodies for plasmalemma vesicle associated protein (PLVAP), a caveolar endothelial marker that cannot be accessed by rigid particles larger than ∼100 nm. In previous work, 150 nm NGs effectively targeted PLVAP, where rigid particles of similar diameter did not. EOD-modified NGs targeted PLVAP less effectively than unmodified NGs, but more effectively than DODD or DAD modified NGs, which both yielded low levels of targeting, resembling results previously obtained with polystyrene particles. Cross-linked NGs were also conjugated to antibodies against intracellular adhesion molecule-1 (ICAM-1), an endothelial marker accessible to large rigid particles. Cross-linked NGs and unmodified NGs targeted uniformly to ICAM-1. We thus demonstrate cross-linker modification of NGs, AFM determination of NG mechanical properties varying with cross-linker, and tuning of specific sterically constrained vascular targeting behavior in correlation with cross-linker-modified NG mechanical properties.