Orthogonally “Clickable” Biodegradable Nanofibers: Tailoring Biomaterials for Specific Protein Immobilization

Abstract

Multifunctionalizable polymeric nanofibers can be tailored for various biomedical applications by selective conjugation of small molecules and bioactive ligands. This study reports the design, synthesis, and application of novel biodegradable polyester-based nanofibers bearing metal-free “clickable” handles. Polylactide-based polymers were synthesized using organo-catalyzed ring-opening polymerization to contain “clickable” chain-end functional groups that specifically react through radical or nucleophilic thiol–ene reactions. A furan-protected maleimide-containing hydroxyl-bearing initiator yielded polymers containing strained oxanorbornene unit at their chain end. In addition, postpolymerization thermal treatment provides maleimide end group-containing polymers. Solution electrospinning method was utilized to obtain bead-free nanofibers. Efficient conjugation on these nanofibers was demonstrated using metal-free conjugation reactions. It was observed that polylactide nanofibers undergo extensive biofouling, which limits their possible utilization for specific biomolecular immobilization. To alleviate this problem, polymers were modified to contain two orthogonally reactive functional groups, namely, the oxanorbornene unit and an azide group at their chain ends. The former reactive handle was used for conjugation of poly(ethylene glycol) chains to impart hydrophilicity and thus an antibiofouling ability, whereas the azide group undergoes strain-promoted azide–alkyne cycloaddition to install a protein-binding ligand such as biotin. These nanofibers were able to specifically immobilize the protein streptavidin with minimal nonspecific adsorption.

Multifunctional and Transformable ‘Clickable’ Hydrogel Coatings on Titanium Surfaces: From Protein Immobilization to Cellular Attachment

“…Z1 fluorescence microscope (Carl Zeiss, Jena, Germany). BODIPY derivatives and Alexa Fluor 488 were visualized by filter set 38, TRIT-C conjugated ExtrAvidin was visualized by filter set 43 and DAPI was visualized by filter set 49.…”

“…In particular, the Huisgen 1,3-dipolar cycloaddition [ 29 ], strain-promoted (3+2) azide−alkyne cycloaddition [ 30 , 31 ], radical-mediated thiol-ene [ 32 , 33 ] and thiol-yne [ 34 , 35 ] reactions, Michael additions [ 36 ] and Diels–Alder [ 37 , 38 , 39 , 40 ] reactions have been widely used for immobilization of (bio)molecules on a wide variety of polymeric interfaces. Among all ‘clickable’ units, the maleimide functional group attracts attention due to their facile reaction with thiol- and furan-containing molecules under mild conditions [ 41 , 42 , 43 , 44 ]. We have earlier reported maleimide-containing polymers [ 45 , 46 ], surfaces [ 47 , 48 , 49 , 50 ] and bulk hydrogels [ 51 ] for biomolecular immobilization [ 52 , 53 ].…”

Micropatterned Reactive Nanofibers: Facile Fabrication of a Versatile Biofunctionalizable Interface

“…For many of these applications, nanofibers are functionalized appropriately to render them with specific properties. Over the past decade several efficient chemical transformations have been utilized, many of which are based on the “click” chemistry. − While nanofibers that are stable in aqueous environment can be engineered by using hydrophobic polymers, obtaining hydrophilic nanofibers that are stable in water can be challenging. Stable nanofibers with hydrophilic surfaces can be obtained either through imparting enough physical interactions such as hydrophobic or electrostatic or through the more widely used approach of chemical cross-linking. ,− Chemical cross-linking agents such as glutaraldehyde, glyoxal, and genipin have been extensively used for the cross-linking of various natural and synthetic nanofibers such as collagen, chitosan, poly­(vinyl alcohol), and hybrid fibers such as polycaprolactone/gelatin nanofibers .…”

Electrospinning of Poly(1,4‐Cyclohexanedimethylene Acetylene Dicarboxylate): Study on the Morphology, Wettability, Thermal and Biodegradation Behaviors

“…[22][23][24][25] The importance of fabrication of reactive, clickable and biodegradable polymeric fibers like PCA for several applications has been recently studied and reviewed in the literature. [26][27][28][29] In the light of the all of aforementioned information, herein, PCA fibers were produced from their solutions in chloroform by means of basic electrospinning system under ambient conditions for the first time. The influence of some electrospinning parameters on various properties of PCA is emphasized and the observed results were subsequently compared with non-electrospun PCA sample.…”

“…[ 22–25 ] The importance of fabrication of reactive, clickable and biodegradable polymeric fibers like PCA for several applications has been recently studied and reviewed in the literature. [ 26–29 ]…”