Gradient Copolymer Synthesis through Self-Assembly.

Polymerization-induced self-assembly (PISA) is typically performed to produce polymer nanoparticles featuring specific assembly morphologies. Herein, we demonstrate the use of PISA as a synthetic tool to direct gradient copolymer synthesis. Specifically, we leverage hydrophobicity-induced reaction selectivity and the rate acceleration typically associated with polymer compartmentalization upon assembly during PISA to bias reaction selectivity. In the chain extension of a poly(ethylene glycol) macrochain transfer agent, the selectivity of diacetone acrylamide (DAAm) and N,N-dimethylacrylamide (DMA), two monomers with near-identical reactivity in water, can be modulated in situ such that DAAm is preferentially incorporated over DMA upon self-assembly. By increasing the feed ratio of DAAm, monomer differentiation can be further biased toward DAAm due to the locus of polymerization becoming increasingly hydrophobic. This change in selectivity affords the autonomous generation of DAAm-DMA gradient sequences, otherwise inaccessible without outside intervention. Finally, a mild hydrolysis protocol can then be employed to harvest DAAm-DMA sequences, yielding compositionally unique gradient copolymers.

A silicone-based support material eliminates interfacial instabilities in 3D silicone printing.

Among the diverse areas of 3D printing, high-quality silicone printing is one of the least available and most restrictive. However, silicone-based components are integral to numerous advanced technologies and everyday consumer products. We developed a silicone 3D printing technique that produces precise, accurate, strong, and functional structures made from several commercially available silicone formulations. To achieve this level of performance, we developed a support material made from a silicone oil emulsion. This material exhibits negligible interfacial tension against silicone-based inks, eliminating the disruptive forces that often drive printed silicone features to deform and break apart. The versatility of this approach enables the use of established silicone formulations in fabricating complex structures and features as small as 8 micrometers in diameter.

Leveraging ultra-low interfacial tension and liquid-liquid phase separation in embedded 3D bioprinting.

Many recently developed 3D bioprinting strategies operate by extruding aqueous biopolymer solutions directly into a variety of different support materials constituted from swollen, solvated, aqueous, polymer assemblies. In developing these 3D printing methods and materials, great care is often taken to tune the rheological behaviors of both inks and 3D support media. By contrast, much less attention has been given to the physics of the interfaces created when structuring one polymer phase into another in embedded 3D printing applications. For example, it is currently unclear whether a dynamic interfacial tension between miscible phases stabilizes embedded 3D bioprinted structures as they are shaped while in a liquid state. Interest in the physics of interfaces between complex fluids has grown dramatically since the discovery of liquid-liquid phase separation (LLPS) in living cells. We believe that many new insights coming from this burst of investigation into LLPS within biological contexts can be leveraged to develop new materials and methods for improved 3D bioprinting that leverage LLPS in mixtures of biopolymers, biocompatible synthetic polymers, and proteins. Thus, in this review article, we highlight work at the interface between recent LLPS research and embedded 3D bioprinting methods and materials, and we introduce a 3D bioprinting method that leverages LLPS to stabilize printed biopolymer inks embedded in a bioprinting support material.

Hybrid Block Copolymer Synthesis by Merging Photoiniferter and Organocatalytic Ring-Opening Polymerizations.

Access to block copolymers from monomers that do not polymerize via a common mechanism requires initiation from a multifunctional species that allows orthogonal polymerization chemistries. We disclose a strategy to provide well-defined polyacrylamido-b-polyether block copolymers by a one-pot combination of photoiniferter polymerization and organocatalytic ring-opening polymerization (ROP) using a hydroxy-functionalized trithiocarbonate photoiniferter as the dual initiator at ambient temperature. Our results reveal good compatibility between the two polymerization systems and highlight that they can be performed in arbitrary order or simultaneously with good retention of the thiocarbonylthio functionality. We also demonstrate selective temporal control over the photoiniferter polymerization during concurrent ROP. We harnessed the efficiency of combining these polymerization systems to provide tailor-made block copolymers from chemically distinct monomers.

Synthesis of functional 1,2-dithiolanes from 1,3-bis-tert-butyl thioethers.

We report the one-step synthesis of diversely substituted functional 1,2-dithiolanes by reacting readily accessible 1,3-bis-tert-butyl thioethers with bromine. The reaction proceeds to completion within minutes under mild conditions, presumably via a sulfonium-mediated ring closure. Using X-ray crystallography and UV-vis spectroscopy, we demonstrate how substituent size and ring substitution pattern can affect the geometry and photophysical properties of 1,2-dithiolanes.

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly.

Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL-1 ) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.

Block Copolymer Vitrimers.

In this report, we merge block copolymers with vitrimers in an effort to realize the prospect of higher-order, nanoscale control over associative cross-link exchange and flow. We show the use of controlled polymerization as a vital tool to understand fundamental structure-property effects through the precise control of polymer architecture and molecular weight. Vitrimers derived from self-assembling block copolymers exhibit superior resistance to macroscopic deformation in comparison to their analogs generated from statistical copolymers. Our results suggest that the enhanced creep resistance achieved by control over chain topology in block vitrimers can be used to tune viscoelastic properties. The resistance to macroscopic deformation that arises from a microphase-separated structure in this new class of materials differentiates block vitrimers from their statistical counterparts and introduces the potential of topology-control over viscoelastic flow.

Theranostic nanocarriers combining high drug loading and magnetic particle imaging.

We report preparation of theranostic nanocarriers loaded with up to 50 wt% of the anticancer drug doxorubicin that contain magnetic nanoparticles which enable Magnetic Particle Imaging (MPI), an emerging technology for quantitative and unambiguous imaging of the nanocarriers. The nanocarriers, coated with poly(ethylene glycol)-block-poly(lactic acid) (PEG4.9kD-b-PLA6kD) block copolymer for colloidal stability, are composed of a hydrophobic core of precipitated hydrolysable doxorubicin prodrug (proDox) and magnetic nanoparticles. Transmission electron microscopy (TEM) shows evidence of precipitated proDox for nanocarriers with high drug loading of up to 50 wt%. MPI measurements show that the nanocarriers can be quantitatively imaged. The nanocarriers are internalized by MDA-MB-231 cells and their IC50 value via metabolic assay is 1.1 µM, compared to 0.21 µM for free doxorubicin. The release rate from the nanocarriers was dependent on environmental pH. These nanocarriers with high drug loading and quantitative imaging are promising candidates for future applications.

Adaptable Crosslinks in Polymeric Materials: Resolving the Intersection of Thermoplastics and Thermosets.

The classical division of polymeric materials into thermoplastics and thermosets based on covalent network structure often implies that these categories are distinct and irreconcilable. Yet, the past two decades have seen extensive development of materials that bridge this gap through incorporation of dynamic crosslinks, enabling them to behave as both robust networks and moldable plastics. Although their potential utility is significant, the growth of covalent adaptable networks (CANs) has obscured the line between "thermoplastic" and "thermoset" and erected a conceptual barrier to the growing number of new researchers entering this discipline. This Perspective aims to both outline the fundamental theory of CANs and provide a critical assessment of their current status. We emphasize throughout that the unique properties of CANs emerge from the network chemistry, and particularly highlight the role that the crosslink exchange mechanism (i.e., dissociative exchange or associative exchange) plays in the resultant material properties under processing conditions. Predominant focus will be on thermally induced dynamic behavior, as the majority of presently employed exchange chemistries rely on thermal stimulus, and it is simple to apply to bulk materials. Lastly, this Perspective aims to identify current issues and address possible solutions for better fundamental understanding within this field.

Synthesis of functional and boronic acid-containing aliphatic polyesters via Suzuki coupling.

Imparting additional functionalities along the side chains of polyesters remains a challenge due to the laborious nature of monomer synthesis and limited polymer functionalization methods for polyesters. To address this challenge, a carbon-carbon bond forming reaction was studied to introduce pendent functional groups in polylactides. This functionalization approach was applied for preparing boronic acid-containing polylactides, an unexplored class of polymers.

Synthesis of Multifunctional Homopolymers through Using Thiazolidine Chemistry and Post-Polymerization Modification.

Multifunctional homopolymers, defined here as polymers that contain multiple reactive functional groups per repeat unit, are versatile scaffolds for preparing complex macromolecules via post-polymerization modification. However, there are limited methods for preparing multifunctional homopolymers that contain more than one nucleophilic site per repeat unit. Herein, a strategy to synthesize a multifunctional homopolymer using thiazolidine chemistry is demonstrated. Controlled radical polymerization of a thiazolidine-containing acrylamido monomer allows for the synthesis of a polymer with pendent latent nucleophiles. Ring-opening of the thiazolidine affords a homopolymer with two side-chain reactive sites, an amine and a thiol. One-pot functionalization via disulfide formation and acyl substitution is performed to introduce two distinct groups in each repeat unit.

Catalyst-Free Photoinduced End-Group Removal of Thiocarbonylthio Functionality.

An initiator- and catalyst-free method for polymer end-group modification has been designed. Under long-wave ultraviolet irradiation, polymers with thiocarbonylthio end groups undergo photolytic cleavage to reveal an active macroradical capable of irreversible termination with a suitable hydrogen source. This straightforward method was successfully demonstrated by the removal of a range of end groups that commonly result from reversible addition-fragmentation chain transfer or photoiniferter polymerizations, including trithiocarbonate, dithiobenzoate, xanthate, and dithiocarbamate mediating agents. This strategy proved efficient for polymers derived from acrylamido, acrylic, methacrylic, styrenic, and vinylpyrrolidone monomers.