Intrinsically stretchable electrode array enabled in vivo electrophysiological mapping of atrial fibrillation at cellular resolution.

Electrophysiological mapping of chronic atrial fibrillation (AF) at high throughput and high resolution is critical for understanding its underlying mechanism and guiding definitive treatment such as cardiac ablation, but current electrophysiological tools are limited by either low spatial resolution or electromechanical uncoupling of the beating heart. To overcome this limitation, we herein introduce a scalable method for fabricating a tissue-like, high-density, fully elastic electrode (elastrode) array capable of achieving real-time, stable, cellular level-resolution electrophysiological mapping in vivo. Testing with acute rabbit and porcine models, the device is proven to have robust and intimate tissue coupling while maintaining its chemical, mechanical, and electrical properties during the cardiac cycle.

Immunological Properties of Protein-Polymer Nanoparticles.

The covalent attachment of polymers to the surface of proteins and nanoparticles has been widely employed in the development of biomedical platforms capable of delaying or diminishing immune surveillance. The most widely employed polymer for these applications has been poly(ethylene glycol) (PEG), yet recent evidence has suggested that other polymer architectures and compositions provide significantly better in vitro and in vivo properties of protein-polymer hybrid materials. Moreover, few direct comparisons of PEG to these polymers have been reported.

Neural stem cell encapsulation and differentiation in strain promoted crosslinked polyethylene glycol-based hydrogels.

Encapsulated cell viability within crosslinked hydrogels is a critical factor to consider in regenerative medicine/cell delivery applications. Herein, a "click" hydrogel system is presented encompassing 4-dibenzocyclooctynol functionalized polyethylene glycol, a four arm polyethylene glycol tetraazide crosslinker, tethered native protein attachment ligands (laminin), and a tethered potent neurogenic differentiation factor (interferon-γ). With this approach, hydrogel formation occurs via strain-promoted, metal-free, azide-alkyne cycloaddition in an aqueous buffer.

2-Hydroxyethylcellulose and Amphiphilic Block Polymer Conjugates Form Mechanically Tunable and Nonswellable Hydrogels.

Herein, we report a family of mechanically tunable, nonswellable hydrogels that are based on a 2-hydroxyethylcellulose (HEC) scaffold grafted with amphiphilic diblock copolymers. Poly[(oligo(ethylene glycol)methyl ether methacrylate]--poly(methyl methacrylate) (POEGMA--PMMA) diblock copolymers of different compositions were created via RAFT polymerization using an alkyne terminated macro chain transfer agent (CTA). 2-Hydroxyethylcellulose (HEC) was modified with azide groups and the diblock copolymers were attached to the backbone via the copper-catalyzed click reaction to yield HEC--(POEGMA--PMMA) graft terpolymers.

Concentration-Dependent hMSC Differentiation on Orthogonal Concentration Gradients of GRGDS and BMP-2 Peptides.

Self-assembled monolayer substrates containing tethered orthogonal concentration profiles of GRGDS (glycine/arginine/glycine/aspartic acid/serine) and BMP-2 (bone morphogenetic protein) peptides are shown to accelerate or decelerate, depending on the concentrations, the proliferation and osteoblastic differentiation of human mesenchymal stem cell (hMSC) populations in vitro without the use of osteogenic additives in culture medium. Concurrently, the single peptide gradient controls (GRGDS or BMP-2 only) induce significantly different proliferation and differentiation behavior from the orthogonal substrates. Bone sialoprotein (BSP) and Runt-related transcription factor 2 (Runx2) PCR data acquired from hMSC populations isolated by laser capture microdissection correspond spatially and temporally to protein marker data obtained from immunofluorescent imaging tracking of the differentiation process.

Post-Electrospinning "Triclick" Functionalization of Degradable Polymer Nanofibers.

4-Dibenzocyclooctynol (DIBO) was used as an initiator for the ring-opening copolymerization of ε-caprolactone and 1,4,8-trioxaspiro[4.6]-9-undecanone (TOSUO) resulting in a series of DIBO end-functionalized copolymers. Following deprotection of the ketone group, the polymers were derivatized with aminooxyl-containing compounds by oxime ligation.

Enhanced Schwann cell attachment and alignment using one-pot "dual click" GRGDS and YIGSR derivatized nanofibers.

Using metal-free click chemistry and oxime condensation methodologies, GRGDS and YIGSR peptides were coupled to random and aligned degradable nanofiber networks postelectrospinning in a one-pot reaction. The bound peptides are bioactive, as demonstrated by Schwann cell attachment and proliferation, and the inclusion of YIGSR with GRGDS alters the expression of the receptor for YIGSR. Additionally, aligned nanofibers act as a potential guidance cue by increasing the aspect ratio and aligning the actin filaments, which suggest that peptide-functionalized scaffolds would be useful to direct SCs for peripheral nerve regeneration.

Dopamine-Based Copper-Free Click Kit for Efficient Surface Functionalization.

Strain-promoted azide-alkyne cycloaddition reactions are combined with a dopamine functional species to generate a highly efficient method for surface modification. The resulting conjugate containing 4-dibenzocyclooctynol (DIBO) and dopamine results in a versatile surface labeling technology that can replicate patterns generated from photolithography and microcontact printing techniques.

Cascading One-Pot Synthesis of Single-Tailed and Asymmetric Multitailed Giant Surfactants.

Rapid and precise synthesis of macromolecules has been a grand challenge in polymer chemistry. In this letter, we describe a convenient, rapid, and robust strategy for a one-pot synthesis of various precisely defined giant surfactants based on polyhedral oligomeric silsesquioxane (POSS). The method combines orthogonal oxime ligation, strain-promoted azide-alkyne cycloaddition (SPAAC), and thiol-ene "click" coupling.

Peptide-functionalized oxime hydrogels with tunable mechanical properties and gelation behavior.

We demonstrate the formation of polyethylene glycol (PEG) based hydrogels via oxime ligation and the photoinitiated thiol-ene 3D patterning of peptides within the hydrogel matrix postgelation. The gelation process and final mechanical strength of the hydrogels can be tuned using pH and the catalyst concentration. The time scale to reach the gel point and complete gelation can be shortened from hours to seconds using both pH and aniline catalyst, which facilitates the tuning of the storage modulus from 0.

Directed differentiation and neurite extension of mouse embryonic stem cell on aligned poly(lactide) nanofibers functionalized with YIGSR peptide.

End-functional PLLA nanofibers were fabricated into mats of random or aligned fibers and functionalized post-spinning using metal-free "click chemistry" with the peptide Tyr-Ile-Gly-Ser-Arg (YIGSR). Fibers that were both aligned and functionalized with YIGSR were found to significantly increase the fraction of mouse embryonic stem cells (mESC) expressing neuron-specific class III beta-tubulin (TUJ1), the level of neurite extension and gene expression for neural markers compared to mESC cultured on random fiber mats and unfunctionalized matrices. Precise functionalization of degradable polymers with bioactive peptides created translationally-relevant materials that capitalize on the advantages of both synthetic and natural systems, while mitigating the classic limitations of each.

Sequential Triple "Click" Approach toward Polyhedral Oligomeric Silsesquioxane-Based Multiheaded and Multitailed Giant Surfactants.

This letter reports a sequential triple "click" chemistry method for the precise synthesis of functional polyhedral oligomeric silsesquioxane (POSS)-based multiheaded and multitailed giant surfactants. A vinyl POSS-based heterobifunctional building block possessing two alkyne groups of distinct reactivity was used as a robust and powerful "clickable" precursor for ready access to a variety of POSS-based shape amphiphiles with complex architectures. The synthetic approach involves sequentially performed strain-promoted azide-alkyne cycloaddition (SPAAC), copper-catalyzed azide-alkyne cycloaddition (CuAAC), and thiol-ene "click" coupling (TECC).

Cascading "Triclick" functionalization of poly(caprolactone) thin films quantified via a quartz crystal microbalance.

A series of mono- and multifunctionalized degradable polyesters bearing various "clickable" groups, including ketone, alkyne, azide, and methyl acrylate (MA) are reported. Using this approach, we demonstrate a cascade approach to immobilize and quantitate three separate bioactive groups onto poly(caprolactone) (PCL) thin films. The materials are based on tunable copolymer compositions of ε-caprolactone and 2-oxepane-1,5-dione.

Facile fabrication of "dual click" one- and two-dimensional orthogonal peptide concentration gradients.

Peptides, proteins, and extracellular matrix act synergistically to influence cellular function at the biotic-synthetic interface. However, identifying the individual and cooperative contributions of the various combinations and concentration regimes is extremely difficult. The confined channel deposition method we describe affords highly tunable orthogonal reactive concentration gradients that greatly expand the dynamic range, spatial control, and chemical versatility of the reactive silanes that can be controllably deposited.

Strain-Promoted Crosslinking of PEG-based Hydrogels via Copper-Free Cycloaddition.

The synthesis of a 4-dibenzocyclooctynol (DIBO) functionalized polyethylene glycol (PEG) and fabrication of hydrogels via strain-promoted, metal-free, azide-alkyne cycloaddition is reported. The resulting hydrogel materials provide a versatile alternative in which to encapsulate cells that are sensitive to photochemical or chemical crosslinking mechanisms.

Post-assembly derivatization of electrospun nanofibers via strain-promoted azide alkyne cycloaddition.

A primary amine-derivatized 4-dibenzocyclooctynol (DIBO) was used to initiate the ring-opening polymerization of poly(γ-benzyl-L-glutamate) (DIBO-PBLG). This initiator yields well-defined PBLG polymers functionalized with DIBO at the chain termini. The DIBO end group further survives an electrospinning process that yields nanofibers that were then derivatized post-assembly with azide-functionalized gold nanoparticles.