Ostwald ripening for designing time-dependent crystal hydrogels.

Ostwald ripening (OR), a classic solution theory describing molecular transfer from metastable crystal to stable one, is applied to design time-dependent crystal hydrogels that can automatically change their mechanical properties. Using a system made from crosslinked polyacrylamide (PAM) and sodium acetate (NaAc), we demonstrate that metastable fibrous crystal networks of NaAc preferably form in PAM hydrogels via a polymer-involving mismatch nucleation. These fibrous crystals would undergo OR and evolve into isolated bulk crystals, leading to a significant reduction in material rigidity (179 folds) and interfacial adhesion (20 folds). This transformation can be applied to program time-dependent self-recovery in shape and self-delamination. Since OR is a ubiquitous, robust feature of various crystals, the approach reported here represents a new direction for designing advanced transient soft materials.

Transpiration-Induced Self-Growth of Texture Hydrogel Surfaces.

Trees grow by coupling the transpiration-induced nutrient absorption from external sources and photosynthesis-based nutrient integration. Inspired by this manner, we designed a class of polyion complex (PIC) hydrogels containing isolated liquid-filled voids for growing texture surfaces. The isolated liquid-filled voids were created via irreversible matrix reconfiguration in a deswelling-swelling process. During transpiration, these voids reversibly collapse to generate negative pressures within the matrices to extract polymerizable compounds from external sources and deliver them to the surface of the samples for photopolymerization. This growth process is spatial-controllable and can be applied to fabricate complex patterns consisting of different compositions, suggesting a new strategy for making texture surfaces.

Self-Growing Organic Materials.

The growth of living systems is ubiquitous. Living organisms can continually update their sizes, shapes, and properties to meet various environmental challenges. Such a capability is also demonstrated by emerging self-growing materials that can incorporate externally provided compounds to grow as living organisms. In this Minireview, we summarize these materials in terms of six aspects. First, we discuss their essential characteristics, then describe the strategies for enabling crosslinked organic materials to self-grow from nutrient solutions containing polymerizable compounds. The developed examples are grouped into five categories based on their molecular mechanisms. We then explain the mechanism of mass transport within polymer networks during growth, which is critical for controlling the shape and morphology of the grown products. Afterwards, simulation models built to explain the interesting phenomena observed in self-growing materials are discussed. The development of self-growing materials is accompanied by various applications, including tuning bulk properties, creating textured surfaces, growth-induced self-healing, 4D printing, self-growing implants, actuation, self-growing structural coloration, and others. These examples are then summed up. Finally, we discuss the opportunities brought by self-growing materials and their facing challenges.

Rational Design of Bisphosphonate Lipid-like Materials for mRNA Delivery to the Bone Microenvironment.

The development of lipid nanoparticle (LNP) formulations for targeting the bone microenvironment holds significant potential for nucleic acid therapeutic applications including bone regeneration, cancer, and hematopoietic stem cell therapies. However, therapeutic delivery to bone remains a significant challenge due to several biological barriers, such as low blood flow in bone, blood-bone marrow barriers, and low affinity between drugs and bone minerals, which leads to unfavorable therapeutic dosages in the bone microenvironment. Here, we construct a series of bisphosphonate (BP) lipid-like materials possessing a high affinity for bone minerals, as a means to overcome biological barriers to deliver mRNA therapeutics efficiently to the bone microenvironment in vivo. Following in vitro screening of BP lipid-like materials formulated into LNPs, we identified a lead BP-LNP formulation, 490BP-C14, with enhanced mRNA expression and localization in the bone microenvironment of mice in vivo compared to 490-C14 LNPs in the absence of BPs. Moreover, BP-LNPs enhanced mRNA delivery and secretion of therapeutic bone morphogenetic protein-2 from the bone microenvironment upon intravenous administration. These results demonstrate the potential of BP-LNPs for delivery to the bone microenvironment, which could potentially be utilized for a range of mRNA therapeutic applications including regenerative medicine, protein replacement, and gene editing therapies.

Photoinduced Strain-Assisted Synthesis of a Stiff-Stilbene Polymer by Ring-Opening Metathesis Polymerization.

Developing a novel strategy to synthesize photoresponsive polymers is of significance owing to their potential applications. We report a photoinduced strain-assisted synthesis of main-chain stiff-stilbene polymers by using ring-opening metathesis polymerization (ROMP), activating a macrocyclic π-bond connected to a stiff-stilbene photoswitch through a linker. Since the linker acts as an external constraint, the photoisomerization to the E-form leads to the stiff-stilbene being strained and thus reactive to ROMP. The photoisomerization of Z-form to E-form was investigated using time-dependent NMR studies and UV/Vis spectroscopy. The DFT calculation showed that the E-form was less stable due to a lack of planarity. By the internal strain developed due to the linker constraint through photoisomerization, the E-form underwent ROMP by a second generation Grubbs catalyst. In contrast, Z-form did not undergo polymerization under similar conditions. The MALDI-TOF spectrum of E-form after polymerization showed the presence of oligomers of >5.2 kDa.

Reversible Bacterial Adhesion on Mixed Poly(dimethylaminoethyl methacrylate)/Poly(acrylamidophenyl boronic acid) Brush Surfaces.

A simple and versatile method for the preparation of surfaces to control bacterial adhesion is described. Substrates were first treated with two catechol-based polymerization initiators, one for thermal initiation and one for visible-light photoinitiation. Graft polymerization in sequence of dimethylaminoethyl methacrylate (DMAEMA) and 3-acrylamidebenzene boronic acid (BA) from the surface-bound initiators to form mixed polymer brushes on the substrate was then carried out. The PDMAEMA grafts were thermally initiated and the PBA grafts were visible-light-photoinitiated. Gold, poly(vinyl chloride) (PVC), and poly(dimethylsiloxane) (PDMS) were used as model substrates. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), and ellipsometry analysis confirmed the successful grafting of PDMAEMA/PBA mixed brushes. We demonstrated that the resulting surfaces showed charge-reversal properties in response to change of pH. The transition in surface charge at a specific pH allowed the surface to be reversibly switched from bacteria-adhesive to bacteria-resistant. At pH 4.5, below the isoelectric points (IEP, pH 5.3) of the mixed brushes, the surfaces are positively charged and the negatively charged Gram-positive S. aureus adheres at high density (2.6 × 10(6) cells/cm(2)) due to attractive electrostatic interactions. Subsequently, upon increasing the pH to 9.0 to give negatively charged polymer brush surface, ∼90% of the adherent bacteria are released from the surface, presumably due to repulsive electrostatic interactions. This approach provides a simple method for the preparation of surfaces on which bacterial adhesion can be controlled and is applicable to a wide variety of substrates.

A versatile, fast, and efficient method of visible-light-induced surface grafting polymerization.

To overcome the problem caused by the lability of the Au-S bond, we demonstrate the first use of Mn2(CO)10 for visible-light-induced surface grafting polymerization on Au surfaces in this paper. The visible-light-induced surface grafting of poly(N-isopropylacrylamide) (PNIPAAm) has the features of a "controlled" polymerization, which is characterized by a linear relationship between the thickness of the grafting layer and the monomer concentration. Ellipsometry indicated the formation of PNIPAAm films of up to ∼200 nm in thickness after only 10 min of polymerization at room temperature, demonstrating that this is a very fast process in comparison with traditional grafting polymerization techniques. Moreover, to demonstrate the potential applications of our approach, different substrates grafted by PNIPAAm and the covalent immobilization of a range of polymers on Au surfaces were also demonstrated. Considering the advantages of simplicity, efficiency, and mild reaction conditions as well as the ability of catecholic derivatives to bind to a large variety of substrates, this visible-light-induced grafting method is expected to be useful in designing functional interfaces.

High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models.

Lipid nanoparticles for delivering mRNA therapeutics hold immense promise for the treatment of a wide range of lung-associated diseases. However, the lack of effective methodologies capable of identifying the pulmonary delivery profile of chemically distinct lipid libraries poses a significant obstacle to the advancement of mRNA therapeutics. Here we report the implementation of a barcoded high-throughput screening system as a means to identify the lung-targeting efficacy of cationic, degradable lipid-like materials. We combinatorially synthesize 180 cationic, degradable lipids which are initially screened in vitro. We then use barcoding technology to quantify how the selected 96 distinct lipid nanoparticles deliver DNA barcodes in vivo. The top-performing nanoparticle formulation delivering Cas9-based genetic editors exhibits therapeutic potential for antiangiogenic cancer therapy within a lung tumor model in female mice. These data demonstrate that employing high-throughput barcoding technology as a screening tool for identifying nanoparticles with lung tropism holds potential for the development of next-generation extrahepatic delivery platforms.

Combinatorial design of siloxane-incorporated lipid nanoparticles augments intracellular processing for tissue-specific mRNA therapeutic delivery.

Systemic delivery of messenger RNA (mRNA) for tissue-specific targeting using lipid nanoparticles (LNPs) holds great therapeutic potential. Nevertheless, how the structural characteristics of ionizable lipids (lipidoids) impact their capability to target cells and organs remains unclear. Here we engineered a class of siloxane-based ionizable lipids with varying structures and formulated siloxane-incorporated LNPs (SiLNPs) to control in vivo mRNA delivery to the liver, lung and spleen in mice. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy. Using organ-specific SiLNPs to deliver gene editing machinery, we achieve robust gene knockout in the liver of wild-type mice and in the lungs of both transgenic GFP and Lewis lung carcinoma (LLC) tumour-bearing mice. Moreover, we showed effective recovery from viral infection-induced lung damage by delivering angiogenic factors with lung-targeted Si5-N14 LNPs. We envision that our SiLNPs will aid in the clinical translation of mRNA therapeutics for next-generation tissue-specific protein replacement therapies, regenerative medicine and gene editing.

Reversibly growing crosslinked polymers with programmable sizes and properties.

Growth constitutes a powerful method to post-modulate materials' structures and functions without compromising their mechanical performance for sustainable use, but the process is irreversible. To address this issue, we here report a growing-degrowing strategy that enables thermosetting materials to either absorb or release components for continuously changing their sizes, shapes, compositions, and a set of properties simultaneously. The strategy is based on the monomer-polymer equilibrium of networks in which supplying or removing small polymerizable components would drive the networks toward expansion or contraction. Using acid-catalyzed equilibration of siloxane as an example, we demonstrate that the size and mechanical properties of the resulting silicone materials can be significantly or finely tuned in both directions of growth and decomposition. The equilibration can be turned off to yield stable products or reactivated again. During the degrowing-growing circle, material structures are selectively varied either uniformly or heterogeneously, by the availability of fillers. Our strategy endows the materials with many appealing capabilities including environment adaptivity, self-healing, and switchability of surface morphologies, shapes, and optical properties. Since monomer-polymer equilibration exists in many polymers, we envision the expansion of the presented strategy to various systems for many applications.

Growing Strategy for Postmodifying Cross-Linked Polymers' Bulky Size, Shape, and Mechanical Properties.

Living organisms are open systems that can incorporate externally provided nutrients to vary their appearances and properties, while synthetic materials normally have fixed sizes, shapes, and functions. Herein, we report a strategy for enabling cross-linked polymers to continuously grow with programmable bulky structures and properties. The growing strategy involves repeatable processes including swelling of polymerizable components into the cross-linked polymers, in situ polymerization of the components, and homogenization of the original and newborn polymer networks. Using acrylate-based polymers as an example, we demonstrate that homogenization allows the grown polymer materials to further integrate various polymerizable components to alternate their bulky properties. During the growth, the changes from elastomers to organogels and then to hydrogels with updated covalent-linked functions (i.e., photochromism and thermoresponsiveness) are shown. Since this growing strategy is applicable to different acrylate systems, we envision its great potential in the design of next-generation polymers, smartening systems, and postmodification of cross-linked polymer materials.

Light-regulated growth from dynamic swollen substrates for making rough surfaces.

Natural organic structures form via a growth mode in which nutrients are absorbed, transported, and integrated. In contrast, synthetic architectures are constructed through fundamentally different methods, such as assembling, molding, cutting, and printing. Here, we report a photoinduced strategy for regulating the localized growth of microstructures from the surface of a swollen dynamic substrate, by coupling photolysis, photopolymerization, and transesterification together. Photolysis is used to generate dissociable ionic groups to enhance the swelling ability that drives nutrient solutions containing polymerizable components into the irradiated region, photopolymerization converts polymerizable components into polymers, and transesterification incorporates newly formed polymers into the original network structure. Such light-regulated growth is spatially controllable and dose-dependent and allows fine modulation of the size, composition, and mechanical properties of the grown structures. We also demonstrate the application of this process in the preparation of microstructures on a surface and the restoration of large-scale surface damage.

Phototriggered Growth and Detachment of Polymer Brushes with Wavelength Selectivity.

Both phototriggered growth and removal of polymer chains from surfaces are efficient ways to finely tune interface properties. Combining these two capabilities in one system with independent control can significantly increase the feasibility of photoregulation on surface modification but has not been reported yet. Herein we describe a novel approach to control both the growth and the detachment of polymer brushes independently by light with different wavelengths. The approach is based on a nitrodopamine-based initiator (NO2-BDAM) which contains a catechol structure for surface modification, alkyl bromide group for radical polymerization, and o-nitrophenyl ethyl moiety for photolysis. When dimanganese decacarbonyl (Mn2(CO)10) was applied together with NO2-BDAM as an initiating system, visible light (460 nm) can be used to trigger the site-specific growth of polymer brushes. Resulting polymer brushes can be selectively removed by UV light (360 nm). This method is suitable for different monomers on various substrates, suggesting a facile and robust method to regulate surface properties.

Thermoresponsive Mobile Interfaces with Switchable Wettability, Optical Properties, and Penetrability.

Liquid-based mobile interfaces, in which liquids are being utilized as structural long-term components, have shown their multifunctionality in materials science, such as the hydration layer of polyelectrolyte brushes used for artificial implants, stabilized lubricants for antibiofouling, anti-icing, self-cleaning, optical control, and so forth. However, these currently available systems do not usually show a response to environmental stimuli. Here, we describe a strategy for preparing thermoresponsive mobile interfaces made from novel silicone-based lubricants that display lower critical solution temperature and demonstrate their capabilities on controlling in situ water wetting and dewetting, thermo-gating penetration, and optical properties. These properties allow the mobile films to form a kind of erasable recording platforms. We foresee diverse applications in liquid transport, wetting and adhesion control, and transport switching.

Antibacterial surfaces based on poly(cationic liquid) brushes: switchability between killing and releasing via anion counterion switching.

The development of a smart antibacterial surface that can both kill attached live bacteria and release dead bacteria is reported. The surface consists of counterion-responsive poly(cationic liquid) brushes of poly(1-(2-methacryloyloxyhexyl)-3-methylimidazolium bromide) (PIL(Br)), the properties of which can be switched repeatedly between bacterial killing and bacterial release. Upon counter-anion exchange of PIL(Br) chains using lithium bis(trifluoromethanesulfonyl) amide (LiTf2N) to yield PIL(Tf2N), the wettability of the surface changes from hydrophilic (water contact angle ∼52°) to hydrophobic (∼97°). The PIL(Br) chains adopt an extended conformation with bactericidal properties. Counter-anion switching to PIL(Tf2N) gives a collapsed chain conformation allowing the release of killed bacteria. The switchable killing and releasing actions of the surface were maintained over three cycles. Thus it is concluded that PIL(Br) layers provide a viable approach for the fabrication of "smart" antibacterial surfaces.

Efficient Transfection by Using PDMAEMA-Modified SiNWAs as a Platform for Ca(2+)-Dependent Gene Delivery.

The major bottleneck for gene delivery lies in the lack of safe and efficient gene vectors and delivery systems. In order to develop a much safer and efficient transfection system, a novel strategy of combining traditional Ca(2+)-dependent transfection with cationic polymer poly(N,N-dimethylamino)ethyl methacrylate (PDMAEMA) modified silicon nanowire arrays (SiNWAs) was proposed in this work. Detailed studies were carried out on the effects of the PDMAEMA polymerization time, the Ca(2+) concentration, and the incubation time of Ca(2+)@DNA complex with PDMAEMA-modified SiNWAs (SN-PDM) on the gene transfection in the cells. The results demonstrated that the transfection efficiency of SN-PDM assisted traditional Ca(2+)-dependent transfection was significantly enhanced compared to those without any surface assistance, and SN-PDM with polymerization time 24 h exhibited the highest efficiency. Moreover, the optimal transfection efficiency was found at the system of a complex containing Ca(2+) (100 mM) and plasmid DNA (pDNA) incubated on SN-PDM for 20 min. Compared with unmodified SiNWAs, SN-PDM has little cytotoxicity and can improve cell attachment. All of these results demonstrated that SN-PDM could significantly enhance Ca(2+)-dependent transfection; this process depends on the amino groups' density of PDMAEMA on the surface, the Ca(2+) concentration, and the available Ca(2+)@DNA complex. Our study provides a potential novel and excellent means of gene delivery for therapeutic applications.

Substrate-independent, Schiff base interactions to fabricate lysine-functionalized surfaces with fibrinolytic activity.

Mimicking natural fibrinolytic mechanisms that covalently bind lysine-ligands (free ε-amino and carboxylic groups) onto biomaterial surfaces is an attractive strategy to prevent clot formation on blood contact materials. However, the modification process is typically complicated and limited due to the diversity of biomaterials. Herein, we describe a simple, substrate-independent protocol to prepare a lysine-ligand functionalized layer on biomaterial surfaces. This approach is based on the adsorption and cross-linking of aldehyde-functionalized poly(N-(2,2-dimethoxyethyl)methacrylamide) (APDMEA) and amino-functionalized polymethacryloyl-l-lysine (APMLys) on a variety of substrates, such as polyurethane (PU), polydimethylsiloxane (PDMS), polyvinylchloride (PVC), stainless steel (SS) and cellulose acetate (CA). The lysine-ligand functionalized layer on substrates highly enhanced the specific adsorption of plasminogen from plasma and showed good chemical stability and excellent biocompatibility with L929 cells using the MTT assay. Moreover, for example, after the adsorbed plasminogen was activated and converted into plasmin, the fibrinolytic functionalization of CA was demonstrated using a modified plasma recalcification assay. Collectively, considering the advantages of simplicity, environmental friendliness and substrate-independence, the present study might therefore represent a general approach for the construction of a biointerface with fibrinolytic activity.

A facile approach to modify poly(dimethylsiloxane) surfaces via visible light-induced grafting polymerization.

Tailoring the surface properties of poly(dimethylsiloxane) (PDMS) is essential for the advancement of its applications. However, the modification process is usually complicated and limited due to the chemical inertness of the surfaces of PDMS. Here, we report for the first time, a facile and versatile method for the functional surface modification of PDMS via visible light-induced grafting polymerization at room temperature. This modification is readily achieved in two steps: (1) covalently integrating alkyl bromine into the PDMS networks using a simple mixing procedure and (2) visible light-induced surface grafting polymerization using Mn2(CO)10. We have demonstrated that the PDMS surface can be functionalized with a wide variety of polymers via covalent grafting, such as poly(trifluoroethyl methacrylate) (PTFEMA), poly(N-isopropylacrylamide) (PNIPAAm), poly(acrylic acid) (PAA) and poly(vinyl acetate) (PVAc). As an example, after the grafted PVAc was transformed into its hydrophilic analogue poly(vinyl alcohol) (PVA), anti-biofouling functionalization of PDMS was obtained. The anti-biofouling properties of the functionalized PDMS were demonstrated using cell adhesion and bacterial adhesion tests. Moreover, the grafting kinetics of PVAc showed that this process was fast and efficient.