Multifunctional and spatially controlled bioconjugation to melt coextruded nanofibers

Abstract

Polymeric fibers have drawn recent interest for uses in biomedical technologies that span drug delivery, regenerative medicine, and wound-healing patches, amongst others. We have recently reported a new class of fibrous biomaterials fabricated using coextrusion and a photochemical modification procedure to introduce functional groups onto the fibers. In this report, we extend our methodology to control surface modification density, describe methods to synthesize multifunctional fibers, and provide methods to spatially control functional group modification. Several different functional fibers are reported for bioconjugation, including propargyl, alkene, alkoxyamine, and ketone modified fibers. The modification scheme allows for control over surface density and provides a handle for downstream functionalization with appropriate bioconjugation chemistries. Through the use of multiple orthogonal chemistries, fiber chemistry could be differentially controlled to append multiple modifications. Spatial control on the fiber surface was also realized, leading to reverse gradients of small molecule dyes. One application is demonstrated for pH-responsive drug delivery of an anti-cancer therapeutics. Finally, the introduction of orthogonal chemical modifications onto these fibers allowed for modification with multiple cell-responsive peptides providing a substrate for osteoblast differentiation.

A thiol probe for measuring unfolded protein load and proteostasis in cells

“… 59 . In essence, synthesis of 2-(4-(2-(4-bromophenyl)-1,2-diphenylvinyl)phenoxy)ethan-1-ol ( 1 ): 4-(2-Hydroxyethoxy)benzophenone ( 2 ) was synthesised according to previous literature 60 . To a solution of 2 (2 mmol, 484 mg), 4-bromobenzophenone (4 mmol, 1.04 g) and zinc powder (14.4 mmol, 941 mg) in dry THF, TiCl 4 (7.2 mmol, 0.79 ml) was added dropwise at –78 °C.…”

Poly(lactic‐co‐glycolic acid) devices: Production and applications for sustained protein delivery

“…Successful delivery of surface attached proteins requires that the attachment can be released over time via hydrolysis, degradation, or specific enzymatic activity (Kim, Lee, & Pokorski, 2017;Zomer Volpato et al, 2012;Zou, Yang, Chen, & Li, 2011). While surface attachment has been effective, it requires excess protein and extensive washing steps for attachment and the loading of proteins on the surface can suffer from batch-to-batch variability (Kim, Wallat, Harker, Advincula, & Pokorski, 2015;Luo et al, 2010). PLGA micro-and nanoparticles produced via electrospraying are not typically subjected to surface modification and the bioactive agent is encapsulated within the particle.…”

A general strategy for generating gradients of bioactive proteins on electrospun nanofiber mats by masking with bovine serum albumin

“…To fabricate a gradient of covalently immobilized drug or peptide on the surface of extruded polymer nanofibers, Kim et al exposed pre-deposited benzophenone to UV light under a gradient photomask and then immobilized the biochemical cue via a click-chemistry reaction. 29 This particular strategy allows for an unprecedented control over the gradient profile and can incorporate as many different protein gradients as there are orthogonal click-chemistry reactions. As a major drawback, this strategy requires the use of specially functionalized benzophenone compounds and proteins.…”