Magnetically actuated glaucoma drainage devicefor regulating intraocular pressure afterimplantation

The key risk factor for glaucoma is increased intraocular pressure (IOP). Glaucoma drainage devices implanted in theeye can reduce IOP and thus stop disease progression. However, most devices currently used in clinical practice arepassive and do not allow for postsurgical IOP control, which may result in serious complications such as hypotony (i.e.,excessively low IOP). To enable noninvasive IOP control, we demonstrate a novel, miniature glaucoma implant that willenable the repeated adjustment of the hydrodynamic resistance after implantation. This is achieved by integrating amagnetic microvalve containing a micropencil-shaped plug that is moved using an external magnet, thereby openingor closing fluidic channels. The microplug is made from biocompatible poly(styrene-block-isobutylene-block-styrene)(SIBS) containing iron microparticles. The complete implant consists of an SIBS drainage tube and a housing elementcontaining the microvalve and fabricated with hot embossing using femtosecond laser-machined glass molds. Usingin vitro and ex vivo microfluidic experiments, we demonstrate that when the microvalve is closed, it can providesufficient hydrodynamic resistance to overcome hypotony. Valve function is repeatable and stable over time. Due to itssmall size, our implant is a promising, safe, easy-to-implant, minimally invasive glaucoma surgery device.

Review:Fabrication and Application of Zwitterion-based Functional Coatings

Zwitterion-based materials by virtue of their special physical and chemical characteristics have attracted researchers to utilize them for fabricating functional coatings. The simultaneous presence of positive and negative charges renders the zwitterion-based materials with electrostatically induced hydration properties, which enables a high resistance towards oily pollutants, nonspecific protein adsorption, bacterial adhesion and biofilm formation. This review starts from the working mechanism of zwitterions and covers the fabrication strategies of zwitterion-based functional coatings, namely the zwitterion-bearing binder route, the zwitterion-bearing additive route and the post-generation of coatings containing zwitterionic precursors. The applications of zwitterion-based functional coatings are discussed, including medical implants, marine antifouling and oil-resistant coatings, with focus on the relevant mechanisms of the zwitterion-containing coatings for a specific performance. Finally, some comments and perspectives on the current situation and future development of zwitterion-based functional coatings are given.

Complex Coacervate Materials as Artificial Cells

CONSPECTUS:Cells have evolved to be self-sustaining compartmentalized systems that consist of many thousands of biomolecules and metabolites interacting in complex cycles and reaction networks.Numerous subtle intricacies of these self-assembled structures are still largely unknown.The importance of liquid−liquid phase separation(both membraneless and mem-brane bound)is,however,recognized as playing an important role in achieving biological function that is controlled in time and space.Reconstituting biochemical reactions in vitro has been a success of the last decades,for example,establishment of the minimal set of enzymes and nutrients able to replicate cellular activities like the in vitro transcription translation of genes to proteins.Further than this though,artificial cell research has the aim of combining synthetic materials and nonliving macromolecules into ordered assemblies with the ability to carry out more complex and ambitious cell-like functions.These activities can provide insights into fundamental cell processes in simplified and idealized systems but could also have an applied impact in synthetic biology and biotechnology in the future.To date,strategies for the bottom-up fabrication of micrometer scale life-like artificial cells have included stabilized water-in-oil droplets,giant unilamellar vesicles(GUV’s),hydrogels,and complex coacervates.Water-in-oil droplets are a valuable and easy to produce model system for studying cell-like processes;however,the lack of a crowded interior can limit these artificial cells in mimicking life more closely.Similarly membrane stabilized vesicles,such as GUV’s,have the additional membrane feature of cells but still lack a macromolecularly crowded cytoplasm.Hydrogel-based artificial cells have a macromolecularly dense interior(although cross-linked)that better mimics cells,in addition to mechanical properties more similar to the viscoelasticity seen in cells but could be seen as being not dynamic in nature and limiting to the diffusion of biomolecules.On the other hand,liquid−liquid phase separated complex coacervates are an ideal platform for artificial cells as they can most accurately mimic the crowded,viscous,highly charged nature of the eukaryotic cytoplasm.Other important key features that researchers in the field target include stabilizing semipermeable membranes,compartmentalization,information transfer/communication,motility,and metabolism/growth.In this Account,we will briefly cover aspects of coacervation theory and then outline key cases of synthetic coacervate materials used as artificial cells(ranging from polypeptides,modified polysaccharides,polyacrylates,and polymethacrylates,and allyl polymers),finishing with envisioned opportunities and potential applications for coacervate artificial cells moving forward.

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues.The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response.Here,three-dimensional melt electrowritten(i.e.,poly(ε-caprolactone))scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells(hPDLSCs)and mediate macrophage polarization.The investigated tissue-specific scaffold attributes comprised fiber morphology(aligned vs.random)and highly-ordered architectures with distinct strand spacings(small 250μm and large 500μm).Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds,while maintaining their round-shape on randomly-oriented fibrous scaffolds.Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds.While hPDLSCs on the scaffolds with 500μm strand spacing show higher expression of osteogenic marker(Runx2)over 21 days,cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers.In an orthotopic mandibular fenestration defect model,findings revealed that the tissue-specific scaffolds(i.e.,aligned fibers for periodontal ligament and highly-ordered 500μm strand spacing fluorinated calcium phosphate[F/CaP]-coated fibers for bone)could enhance the mimicking of regeneration of natural periodontal tissues.

Supramolecular Single-Chain Polymeric Nanoparticles

Nature has unparalleled control over the conforma-tion and dynamics of its folded macromolecular structures.Nature’s ability to arrange amino acids into a precise spatial organization by way of folding allows proteins to fulfill specific functions in an ex-tremely efficient manner.

Translating the action of molecular motors to supramolecular polymers

The amplification of asymmetry from the molecular level to the macroscopic scale is an intriguing mechanism operative in natural systems to control complex functions.Inspired by nature,strategies for transferring chiral information across length scales in purely synthetic systems have been investigated.[1,2]Thereof,chiral molecules are embedded into well-defined ordered supramolecular structures with the dynamics of noncovalent interactions leading to the amplification effect.

Ultrasmall,elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers

To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity,and well-defined spatial and temporal resolutions,a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media(nano-XRCM)as dual-modality imaging agents for positron emission tomography(PET)and computed tomography(CT)has been established.Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide)acrylate monomers,the amphiphilic statistical iodocopolymers(ICPs)could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations(>140 mg iodine/mL water)and comparable viscosities to conventional small molecule XRCM.The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca.10 nm in water was confirmed by dynamic and static light scattering techniques.In a breast cancer mouse model,in vivo biodistribution studies revealed that the64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents.PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals,while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection,enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

Supramolecular Polymerization of Hydrogen-Bonded Trimers in Bulk and Aqueous Medium

Synthetic molecules that form functional noncovalent assemblies in water have received much attention for their potential applications as biomaterials.In this work,we introduce a novel water-compatible monomer based on the phthalhydrazide moiety that assembles into hydrogen-bonded trimeric discs.In bulk,the material exhibits a cylindrical nanostructure in the liquid-crystalline phase at elevated temperatures,morphologically distinct from the crystalline lamellar phase.In water,these molecules effectively form cylinders in a one-dimensional fashion,yielding fibrous structures.The formation of these supramolecular polymers follows a cooperative mechanism,as evidenced by denaturation studies.The trimerized pattern represents a new category of aqueous su pramolecular polymers with future prospects for functional complex molecular systems.

A Versatile BenzimidazoleSubstituted Spirolactam Mechanophore:When Excited State Intramolecular Proton Transfer Couples with Rhodamine

Exploration of multicolor mechanochromic bulk polymers based on a single mechanophore is a big challenge to date.Herein,we report a versatile benzimidazole-substituted spirolactam mechanophore where excited state intramolecular proton transfer(ESIPT)coupled with rhodamine.The mechanophore was facilely synthesized and then covalently linked to polyurethane(PU)chains.The PU film containing the mechanophore(1@PU)showed cooperative photochromism upon irradiation involving simultaneous enhancement of normalized enol and rhodol emissions based on a cooperative ESIPT process and the ring-opening reaction of spirolactam.Moreover,the film exhibited dual-mode multicolor mechanochromism upon stretching and compression.The normalized intensity of enol emission increased and the fluorescence turned from light green to cyan after stretching,then red coloration appeared from colorless after compressing.Control experiments and density functional theory calculations confirmed that the stretch-induced increase of enol emission was attributed to torsion of the dihedral angle between xanthene and benzimidazole in the mechanophore via force-induced disaggregation and direct force action on the isolated mechanophore.Torsion of the dihedral angle and the ring-opening reaction of spirolactam in a single mechanophore occurred sequentially during compression,resulting in an observed red coloration.This study might provide a glimpse into the design of novel multicolor mechanochromic mechanophores.

Amphiphilic AIEgen-polymer aggregates:Design,self-assembly and biomedical applications

Aggregation-induced emission(AIE)is a phenomenon in which fluorescence is enhanced rather than quenched upon molecular assembly.AIE fluorogens(AIEgens)are flexible,conjugated systems that are limited in their dynamics when assembled,which improves their fluorescent properties.This intriguing feature has been incorporated in many different molecular assemblies and has been extended to nanoparticles composed of amphiphilic polymer building blocks.The integration of the fascinating AIE design principle with versatile polymer chemistry opens up new frontiers to approach and solve intrinsic obstacles of conventional fluorescent materials in nanoscience,including the aggregation-caused quenching effect.Furthermore,this integration has drawn significant attention from the nanomedicine community,due to the additional advantages of nanoparticles comprising AIEgenic molecules,such as emission brightness and fluorescence stability.In this regard,a range of AIEgenic amphiphilic polymers have been developed,displaying enhanced emission in the self-assembly/aggregated state.AIEgenic assemblies are regarded as attractive nanomaterials with inherent fluorescence,which display promising features in a biomedical context,for instance in biosensing,cell/tissue imaging and tracking,as well as(photo)therapeutics.In this review,we describe recent strategies for the design and synthesis of novel types of AIEgenic amphiphilic polymers via facile approaches including direct conjugation to natural/synthetic polymers,polymerization,post-polymerization and supramolecular host−guest interactions.Their self-assembly behavior and biomedical potential will be discussed.

Vascularization mediated by mesenchymalstem cells from bone marrow and adiposetissue: a comparison

Tissue-engineered constructs are promising to overcome shortage of organ donors and to reconstruct at least partsof injured or diseased tissues or organs. However, oxygen and nutrient supply are limiting factors in many tissues,especially after implantation into the host. Therefore, the development of a vascular system prior to implantationappears crucial. To develop a functional vascular system, different cell types that interact with each other need tobe co-cultured to simulate a physiological environment in vitro. This review provides an overview and a comparison ofthe current knowledge of co-cultures of human endothelial cells (ECs) with human adipose tissue-derived stem/stromal cells (ASCs) or bone marrow-mesenchymal stem cells (BMSCs) in three dimensional (3D) hydrogel matrices.Mesenchymal stem cells (MSCs), BMSCs or ASCs, have been shown to enhance vascular tube formation of ECs and toprovide a stabilizing function in addition to growth factor delivery and permeability control for ECs. Althoughphenotypically similar, MSCs from different tissues promote tubulogenesis through distinct mechanisms. In this report,we describe differences and similarities regarding molecular interactions in order to investigate which of these two celltypes displays more favorable characteristics to be used in clinical applications. Our comparative study shows that ASCsas well as BMSCs are both promising cell types to induce vascularization with ECs in vitro and consequently arepromising candidates to support in vivo vascularization.

Liquid crystal-based structural color actuators

Animals can modify their body shape and/or color for protection,camouflage and communication.This adaptability has inspired fabrication of actuators with structural color changes to endow soft robots with additional functionalities.Using liquid crystal-based materials for actuators with structural color changes is a promising approach.In this review,we discuss the current state of liquid crystal-based actuators with structural color changes and the potential applications of these structural color actuators in soft robotic devices.