3D Printed Bioactive PLGA Dermal Scaffold for Burn Wound Treatment.

Burn injury represents a major global public healthcare problem and has a significant health-economics impact. In this study, we report on a 3D printed poly(lactic-co-glycolic acid) (PLGA) dermal scaffold containing bioactive PLGA for burn wound healing. Bioactive brush copolymers containing pendant side chains of PLGA and PEGylated Arg-Gly-Asp tripeptide (RGD) or hyaluronic acid (HA) were synthesized by ring-opening metathesis polymerization (ROMP). These copolymers exhibited good thermal stability for material processing using melt-extrusion-based methods. The copolymers were blended with commercial PLGA, extruded into filaments and 3D printed using fused filament fabrication (FFF) methods with incorporated porosities. The 3D printed scaffolds demonstrated good biocompatibility in in vitro cell assays and in vivo murine models. Porcine study based on partial thickness burn wound model showed that these PLGA scaffolds facilitated re-epithelization with reduced inflammation as compared to the clinical gold standard for second-degree burn wound treatment, Biobrane. The bioactive PLGA scaffolds presented herein are beneficial in wound healing and have therapeutic potential in burn wounds treatment.

Bioactive PCL-Peptide and PLA-Peptide Brush Copolymers for Bone Tissue Engineering.

We report the modular synthesis of bioactive brush-type polycaprolactone-peptide and polylactide-peptide copolymers for applications in bone tissue engineering. The brush copolymers containing pendant side chains of polycaprolactone (PCL) or polylactide (PLA) and PEGylated peptides, including linear Arg-Gly-Asp and collagen-like peptide (Gly-Pro-Hyp)3, were synthesized by ring-opening metathesis polymerization with high conversions and low dispersities (<1.5). These PCL-peptide and PLA-peptide copolymers exhibited good thermal stability for material processing using melt-extrusion-based methods. The copolymers were blended with commercial PCL or PLA, extruded into filaments, and 3D printed using fused filament fabrication methods. These bioactive PCL and PLA materials promoted osteogenic differentiation in vitro and showed good biocompatibility in in vivo murine model study. The promising results presented herein will serve as a useful guide for the design and functionalization of PCL or PLA materials for use in bone tissue engineering.

Synthesis of Cyclobutadienoid-Fused Phenazines with Strongly Modulated Degrees of Antiaromaticity.

The streamlined synthesis of a series of regioisomeric azaacene analogues containing fused phenazine and antiaromatic cyclobutadienoids (CBDs), using a catalytic arene-oxanorbornene annulation, followed by aromatization is reported. Controlling the fusion patterns allowed strong modulation of local antiaromaticity. Enhancing antiaromaticity in these regioisomeric azaacenes led to stabilized LUMO, reduced band gap, and quenched fluorescence. This synthetic strategy provides a facile means to fuse CBDs with variable degrees of antiaromaticity onto N-heteroarenes to tune their optoelectronic properties.

Regioselective Synthesis of [3]Naphthylenes and Tuning of Their Antiaromaticity.

Polycyclic conjugated hydrocarbons containing four-membered cyclobutadienoids (CBDs) are of great fundamental and technical interest due to the antiaromaticity brought by CBD circuits. However, their synthesis has been challenging, hampering the exploration and understanding of such systems. We report efficient synthesis of a series of unprecedented [3]naphthylene regioisomers in high yields, where three naphthalenoids are fused through two CBDs in linear, angular, and bent regioconnectivity. Their synthesis was enabled by exclusively regioselective catalytic arene-norbornene annulation (CANAL) between dibromonaphthalenes and benzooxanorbornadienes, followed by aromatization. [3]Naphthylene regioisomers exhibited distinct optoelectronic properties. Nucleus-independent chemical shift calculations, NMR spectroscopy, and X-ray crystallography revealed the strong effect of the fusion pattern on the local antiaromaticity and aromaticity in fused CBDs and naphthalenoids, respectively. Thus, our synthetic strategy allows facile access to extended CBD-fused π-systems with tunable local antiaromaticity and aromaticity.

Synthesis of Ladder Polymers: Developments, Challenges, and Opportunities.

Ladder polymers are unique in that their backbones consist of fused rings with adjacent rings having two or more atoms in common. The restriction of bond rotations in rigid ladder polymers greatly limits their conformational freedom, leading to many intriguing and unique properties. As a non-traditional type of polymers, rigid ladder polymers are of great fundamental interest and technical importance as advanced materials for applications such as membrane gas separation and organic electronics. Ladder polymers can be divided into non-conjugated (with kinked conformations) and conjugated (with planar conformations) structures. Their synthesis can be broadly classified into two general strategies: direct ladder polymerization, and zipping of a linear precursor polymer. This Concept article outlines the historical development of ladder polymers and the chemical strategies used for their synthesis; highlights the challenges associated with their synthesis and characterization, and presents opportunities and outlooks for this unique and intriguing type of polymers.

Streamlined Synthesis of Polycyclic Conjugated Hydrocarbons Containing Cyclobutadienoids via C-H Activated Annulation and Aromatization.

The juxtaposition of fused cyclobutadienoid (CBD) with benzenoid creates intriguing alternating antiaromatic and aromatic conjugation. Synthetic accessibility of such molecules, however, has been challenging and limited in scope. We report a modular and streamlined synthetic strategy to access a large variety of polycyclic conjugated hydrocarbons with fused CBD. Synthesis was achieved through efficient palladium-catalyzed C-H activated annulation between abundant aryl bromides and oxanorbornenes, followed by aromatization under acidic conditions. The influence of four-membered ring was examined using spectroscopy, crystallography, and computation. This strategy will facilitate exploration on the chemical, structural, and electronic properties of such conjugated systems containing CBD.

Functionalized Rigid Ladder Polymers from Catalytic Arene-Norbornene Annulation Polymerization.

Rigid ladder polymers represent a unique polymer architecture but have limited synthetic accessibility and structural diversity. Using catalytic arene-norbornene annulation (CANAL) polymerization, we synthesized ladder polymers consisting of rigid and kinked norbornyl benzocyclobutene backbones and bearing various functional groups, such as alcohol, amine, ester, carbamate, amide, benzyl bromide, azide, and heterocycles. The incorporation of functional groups was achieved by either copolymerization of functionalized ladder-type dinorbornenes or postpolymerization functionalization. Functionalization of ladder polymers allows modification of their solubility, compatibility, and other properties, expanding their utilities. These ladder polymers remain microporous and highly glassy, which are desirable for separation and high-temperature applications.

Efficient synthesis of rigid ladder polymers via palladium catalyzed annulation.

We report a new method to synthesize rigid ladder polymers using efficient palladium catalyzed annulation reactions with low catalyst loading (1 mol %). Rigid ladder polymers with benzocyclobutene backbone linkages can be synthesized from copolymerization of readily accessible aryl dibromides and norbornadiene or polymerization of AB type monomers bearing norbornene and aryl bromide or triflate moieties. High molecular weight (10-40 kDa) rigid ladder polymers can be obtained with complete monomer conversions. Diverse monomers also gave different, fixed ladder polymer conformations. The ladder polymers exhibited excellent thermal stability, high carbonization yield, and large intrinsic porosity.

Amphiphilic methyleneamino synthon through organic dye catalyzed-decarboxylative aminoalkylation.

The utilization of a photo-induced synthon generated from N-phenyl glycine by an organic dye and visible light irradiation is disclosed. The intermediate could be coupled with either a radical or a nucleophile in a simple operation to afford several natural product-like compounds.