Hierarchically Templated Synthesis of 3D-Printed Crosslinked Cyclodextrins for Lycopene Harvesting.

Plants produce a wide range of bioactive phytochemicals, such as antioxidants and vitamins, which play crucial roles in aging prevention, inflammation reduction, and reducing the risk of cancer. Selectively harvesting these phytochemicals, such as lycopene, from tomatoes through the adsorption method is cost-effective and energy efficient. In this work, a templated synthesis of 3D-printed crosslinked cyclodextrin polymers featuring nanotubular structures for highly selective lycopene harvesting is reported. Polypseudorotaxanes formed by triethoxysilane-based telechelic polyethylene glycols and α-cyclodextrins (α-CDs) are designed as the template to (1) synthetically access urethane-based nanotubular structures at the molecular level, and (2) construct 3D-printed architectures with designed macroscale voids. The polypseudorotaxane hydrogels showed good rheological properties for direct ink writing, and the 3D-printed hydrogels were converted to the desired α-CD polymer network through a three-step postprinting transformation. The obtained urethane-crosslinked α-CD monoliths possess nanotubular structures and 3D-printed voids. They selectively adsorb lycopene from raw tomato juice, protecting lycopene from photo- or thermo-degradations. This work highlights the hierarchically templated synthesis approach in developing functional 3D-printing materials by connecting the bottom-up molecular assembly and synthesis with the top-down 3D architecture control and fabrication.

Study on the Friction and Wear Properties of PEEK against Cortical Bone Tissue Under Different Lubricating Conditions.

The tribological behavior between orthopedic implants and cortical bone is important but usually neglected. Poly(ether-ether-ketone) (PEEK) is a promising material for orthopedic applications. To further understand and improve the interfacial tribological properties between PEEK implant and host bone tissue, a PEEK-cortical bone tribo-pair is designed and fabricated. The frictional and wear performance of such tribo-pair is investigated under different lubricants, i.e., simulated body fluid (SBF), calf serum (CS), hyaluronic acid (HA), and mucin (MUC). The results suggest that MUC solution can be utilized as an artificial natural synovial fluid to improve the tribological properties of PEEK-based implants.

Enhanced Bacterial-Infected Wound Healing by Nitric Oxide-Releasing Topological Supramolecular Nanocarriers with Self-Optimized Cooperative Multi-Point Anchoring.

Polymeric systems that provide cationic charges or biocide-release therapeutics are used to treat the bacteria-infected wound. However, most antibacterial polymers based on topologies with restricted molecular dynamics still do not satisfy the clinical requirements due to their limited antibacterial efficacy at safe concentrations in vivo. Here a NO-releasing topological supramolecular nanocarrier with rotatable and slidable molecular entities is reported to provide conformational freedom to promote the interactions between the carrier and the pathogenic microbes, hence greatly improving the antibacterial performance. With improved contacting-killing and efficient delivery of NO biocide from the molecularly dynamic cationic ligand design, the NO-loaded topological nanocarrier achieves excellent antibacterial and anti-biofilm effects via destroying the bacterial membrane and DNA. MRSA-infected rat model is also brought out to demonstrate its wound-healing effect with neglectable toxicity in vivo. Introducing flexible molecular motions into therapeutic polymeric systems is a general design to enhance the healing of a range of diseases.

Conductive and anti-freezing hydrogels constructed by pseudo-slide-ring networks.

Stretchable, tough, and anti-freezing hydrogels were prepared using partially carboxymethylated polyrotaxanes and polyacrylamides. The carboxylic acid groups of α-cyclodextrins in the polyrotaxane and the amide groups in polyacrylamide are hydrogen-bonded, affording a pseudo-slide-ring network, greatly enhancing the hydrogels' macroscale mechanical properties, anti-freezing features, and electrical conductivity for the fabrication of a cold-temperature strain sensor.

An Integrated Design of a Polypseudorotaxane-Based Sea Cucumber Mimic.

The development of integrated systems that mimic the multi-stage stiffness change of marine animals such as the sea cucumber requires the design of molecularly tailored structures. Herein, we used an integrated biomimicry design to fabricate a sea cucumber mimic using sidechain polypseudorotaxanes with tunable nano-to-macroscale properties. A series of polyethylene glycol (PEG)-based sidechain copolymers were synthesized to form sidechain polypseudorotaxanes with α-cyclodextrins (α-CDs). By tailoring the copolymers' molecular weights and their PEG grafting densities, we rationally tuned the sizes of the formed polypseudorotaxanes crystalline domain and the physical crosslinking density of the hydrogels, which facilitated 3D printing and the mechanical adaptability to these hydrogels. After 3D printing and photo-crosslinking, the obtained hydrogels exhibited large tensile strain and broad elastic-to-plastic variations upon α-CD (de)threading. These discoveries enabled a successful fabrication of a sea cucumber mimic, demonstrating multi-stage stiffness changes.

Advanced Polymer Designs for Direct-Ink-Write 3D Printing.

The rapid development of additive manufacturing techniques, also known as three-dimensional (3D) printing, is driving innovations in polymer chemistry, materials science, and engineering. Among current 3D printing techniques, direct ink writing (DIW) employs viscoelastic materials as inks, which are capable of constructing sophisticated 3D architectures at ambient conditions. In this perspective, polymer designs that meet the rheological requirements for direct ink writing are outlined and successful examples are summarized, which include the development of polymer micelles, co-assembled hydrogels, supramolecularly cross-linked systems, polymer liquids with microcrystalline domains, and hydrogels with dynamic covalent cross-links. Furthermore, advanced polymer designs that reinforce the mechanical properties of these 3D printing materials, as well as the integration of functional moieties to these materials are discussed to inspire new polymer designs for direct ink writing and broadly 3D printing.

Hierarchical-Coassembly-Enabled 3D-Printing of Homogeneous and Heterogeneous Covalent Organic Frameworks.

Covalent organic frameworks (COFs) are crystalline polymers with permanent porosity. They are usually synthesized as micrometer-sized powders or two-dimensional thin films and membranes for applications in molecular storage, separation, and catalysis. In this work, we report a general method to integrate COFs with imine or ß-ketoenamine linkages into three-dimensional (3D)-printing materials. A 3D-printing template, Pluronic F127, was introduced to coassemble with imine polymers in an aqueous environment. By limitation of the degree of imine polycondensation during COF formation, the amorphous imine polymer and F127 form coassembled 3D-printable hydrogels with suitable shear thinning and rapid self-healing properties. After the removal of F127 followed by an amorphous-to-crystalline transformation, three ß-ketoenamine- and imine-based COFs were fabricated into 3D monoliths possessing high crystallinity, hierarchical pores with high surface areas, good structural integrity, and robust mechanical stability. Moreover, when multiple COF precursor inks were employed for 3D printing, heterogeneous dual-component COF monoliths were fabricated with high spatial precision. This method not only enables the development of COFs with sophisticated 3D macrostructure but also facilitates the heterogeneous integration of COFs into devices with interconnected interfaces at the molecular level.

Hierarchical Co-Assembly Enhanced Direct Ink Writing.

Integrating intelligent molecular systems into 3D printing materials and transforming their molecular functions to the macroscale with controlled superstructures will unleash great potential for the development of smart materials. Compared to macromolecular 3D printing materials, self-assembled small-molecule-based 3D printing materials are very rare owing to the difficulties of facilitating 3D printability as well as preserving their molecular functions macroscopically. Herein, we report a general approach for the integration of functional small molecules into 3D printing materials for direct ink writing through the introduction of a supramolecular template. A variety of inorganic and organic small-molecule-based inks were 3D-printed, and their superstructures were refined by post-printing hierarchical co-assembly. Through spatial and temporal control of individual molecular events from the nano- to the macroscale, fine-tuned macroscale features were successfully installed in the monoliths.

Ring Shuttling Controls Macroscopic Motion in a Three-Dimensional Printed Polyrotaxane Monolith.

Amplification of molecular motions into the macroscopic world has great potential in the development of smart materials. Demonstrated here is an approach that integrates mechanically interlocked molecules into complex three-dimensional (3D) architectures by direct-write 3D printing. The design and synthesis of polypseudorotaxane hydrogels, which are composed of α-cyclodextrins and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, and their subsequent fabrication into polyrotaxane-based lattice cubes by 3D printing followed by post-printing polymerization are reported. By switching the motion of the α-cyclodextrin rings between random shuttling and stationary states through solvent exchange, the polyrotaxane monolith not only exhibits macroscopic shape-memory properties but is also capable of converting the chemical energy input into mechanical work by lifting objects against gravity.

Injectable supramolecular hydrogel formed from α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron for sustained MMP-9 shRNA plasmid delivery.

Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(l-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. STATEMENT OF SIGNIFICANCE: To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering.

A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery.

The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro, and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, and also showed a good biocompatibility in vivo. Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy.

Photoenhanced gene transfection by a star-shaped polymer consisting of a porphyrin core and poly(L-lysine) dendron arms.

A star-shaped polymer (PP-PLLD) consisting of a porphyrin (PP) core and poly(L-lysine) dendron arms (PLLD) is synthesized by the click reaction, and its ability to deliver pEGFP is investigated in this paper. It is found that PP-PLLD has a good buffer capacity and can form compact complexes with pEGFP. In vitro assay indicates that PP-PLLD shows photoenhanced gene transfection efficiency. PP-PLLD consisting of only third generation PLLD shows a higher transfected cell number than PEI under a Xe lamp at the N/P ratio of 20, and meanwhile shows a neglectable cytotoxicity to HeLa cells. Therefore, PP-PLLD with suited irradiation is a promising nontoxic and photoinducible effective gene delivery strategy, which should be encouraged in gene therapy.