Modular and Versatile Spatial Functionalization of Tissue Engineering Scaffolds through Fiber‐Initiated Controlled Radical Polymerization

Abstract

Native tissues are typically heterogeneous and hierarchically organized, and generating scaffolds that can mimic these properties is critical for tissue engineering applications. By uniquely combining controlled radical polymerization (CRP), end‐functionalization of polymers, and advanced electrospinning techniques, a modular and versatile approach is introduced to generate scaffolds with spatially organized functionality. Poly‐ε‐caprolactone is end functionalized with either a polymerization‐initiating group or a cell‐binding peptide motif cyclic Arg‐Gly‐Asp‐Ser (cRGDS), and are each sequentially electrospun to produce zonally discrete bilayers within a continuous fiber scaffold. The polymerization‐initiating group is then used to graft an antifouling polymer bottlebrush based on poly(ethylene glycol) from the fiber surface using CRP exclusively within one bilayer of the scaffold. The ability to include additional multifunctionality during CRP is showcased by integrating a biotinylated monomer unit into the polymerization step allowing postmodification of the scaffold with streptavidin‐coupled moieties. These combined processing techniques result in an effective bilayered and dual‐functionality scaffold with a cell‐adhesive surface and an opposing antifouling non‐cell‐adhesive surface in zonally specific regions across the thickness of the scaffold, demonstrated through fluorescent labelling and cell adhesion studies. This modular and versatile approach combines strategies to produce scaffolds with tailorable properties for many applications in tissue engineering and regenerative medicine.

Modulation of Living Cell Behavior with Ultra‐Low Fouling Polymer Brush Interfaces

“…It is generally accepted that the cell adhesion is mediated by a protein preadsorption and correlations between the protein adsorption and cell adhesion were described 22,39–41. Interestingly in our work, even though the fouling resistance from 100% human blood plasma as well as from cell‐free culture medium for all the studied coatings was below the detectable limit of SPR measurements (≈0.1 ng cm −2 ), a certain degree, even very low, of fouling from the cells in culture medium was observed.…”

Architectural Modification of Conformal PEG‐Bottlebrush Coatings Minimizes Anti‐PEG Antigenicity While Preserving Stealth Properties

“…Our work with poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) might offer an alternative, and less disruptive, solution. Specifically, over the past decade, we and others have explored POEGMA as an alternative to linear PEG for biomedical applications . POEGMA is a derivative of PEG with a “bottlebrush” architecture.…”

Cell and Protein Fouling Properties of Polymeric Mixtures Containing Supramolecular Poly(ethylene glycol) Additives

“…2,6,9,11,12 The first proteins to adsorb upon contact with the biomaterial are high mobility proteins, such as albumin. Subsequently, displacement by less abundant proteins with higher affinities occurs, starting with globulin and fibrinogen, and ending with high molecular weight kininogen.…”