Cylinders-in-Undulating-Lamellae Morphology from ABC Bottlebrush Block Terpolymers.

Block polymer self-assembly affords a versatile bottom-up strategy to develop materials with the desired properties dictated by specific symmetries and dimensions. Owing to distinct properties compared with linear counterparts, bottlebrush block polymers with side chains densely grafted on a backbone have attracted extensive attention. However, the morphologies found in bottlebrush block polymers so far are limited, and only lamellar and cylindrical ordered phases have been reported in diblock bottlebrushes. The absence of complex morphologies, such as networks, might originate from the intrinsically stiff backbone architecture. We experimentally investigated the morphologies of nonfrustrated ABC bottlebrush block terpolymers, based on two chemistries, poly(ethylene-alt-propylene)-b-polystyrene-b-poly(dl-lactic acid) (PEP-PS-PLA) and PEP-b-PS-b-poly(ethylene oxide) (PEP-PS-PEO), synthesized by ring-opening metathesis polymerization of norbornene-terminated macromonomers. Structural characterization based on small-angle X-ray scattering and transmission electron microscopy measurements revealed an unprecedented cylinders-in-undulating-lamellae (CUL) morphology with p2 symmetry for both systems. Additionally, automated liquid chromatography was employed to fractionate the PEP-PS-PLA bottlebrush polymer, leading to fractions with a spectrum of morphologies, including the CUL. These findings underscore the significance of macromolecular dispersity in nominally narrow dispersity bottlebrush polymers while demonstrating the power of this fractionation technique.

Crystallization Inhibition in Molecular Liquids by Polymers above the Overlap Concentration (c*): Delay of the First Nucleation Event.

Low concentration polymer additives can significantly alter crystal growth kinetics of molecular liquids and glasses. However, the effect of polymer concentration on nucleation kinetics remains poorly understood. Based on an experimentally determined first nucleation time (time to form the first critical nucleus, t0), we show that the polymer overlap concentration, c*, where polymer coils in the molecular liquid start to overlap with each other, is a critical polymer concentration for efficient inhibition of crystallization of a molecular liquid. The value of t0 is approximately equal to that of the neat molecular liquid when the polymer concentration, c, is below c*, but increases significantly when c > c*. This finding is relevant for effective polymer screening and performance prediction of engineered multicomponent amorphous materials, particularly pharmaceutical amorphous solid dispersions.

Threading-the-Needle: Compatibilization of HDPE/iPP blends with butadiene-derived polyolefin block copolymers.

Management of the plastic industry is a momentous challenge, one that pits enormous societal benefits against an accumulating reservoir of nearly indestructible waste. A promising strategy for recycling polyethylene (PE) and isotactic polypropylene (iPP), constituting roughly half the plastic produced annually worldwide, is melt blending for reformulation into useful products. Unfortunately, such blends are generally brittle and useless due to phase separation and mechanically weak domain interfaces. Recent studies have shown that addition of small amounts of semicrystalline PE-iPP block copolymers (ca. 1 wt%) to mixtures of these polyolefins results in ductility comparable to the pure materials. However, current methods for producing such additives rely on expensive reagents, prohibitively impacting the cost of recycling these inexpensive commodity plastics. Here, we describe an alternative strategy that exploits anionic polymerization of butadiene into block copolymers, with subsequent catalytic hydrogenation, yielding E and X blocks that are individually melt miscible with PE and iPP, where E and X are poly(ethylene-ran-ethylethylene) random copolymers with 6 wt% and 90 wt% ethylethylene repeat units, respectively. Cooling melt blended mixtures of PE and iPP containing 1 wt% of the triblock copolymer EXE of appropriate molecular weight, results in mechanical properties competitive with the component plastics. Blend toughness is obtained through interfacial topological entanglements of the amorphous X polymer and semicrystalline iPP, along with anchoring of the E blocks through cocrystallization with the PE homopolymer. Significantly, EXE can be inexpensively produced using currently practiced industrial scale polymerization methods, offering a practical approach to recycling the world's top two plastics.

Accelerating bone regeneration in cranial defects using an injectable organic-inorganic composite hydrogel.

Bone tissue engineering, as an important and attractive multidisciplinary field, affords a feasible strategy for large bone defects which are difficult to heal without clinical intervention. However, the complicated requirements of bone regeneration result in the imperfect performance of many current materials. Inspired by the composite nature of bone tissues, we proposed an organic-inorganic composite strategy. Specifically, we loaded a bone regeneration drug (simvastatin, SIM) and an inorganic component (strontium hydrogen phosphate (SrHPO4)/beta-tricalcium phosphate (ß-TCP)) to a thermogel, constituted by poly(ε-caprolactone-co-D,L-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-D,L-lactide) (PCLA-PEG-PCLA), with a thermo-induced sol-gel transition, to prepare an injectable composite for bone regeneration in cranial defects. The SIM/(Sr/ß-TCP)/PCLA-PEG-PCLA composite was able to be conveniently injected and it spontaneously filled the defect. The appropriate mechanical strength obtained by thermogelation under the stimuli of the body temperature provided the necessary support while the capacity of loading drugs and bioceramics offered bioactivity and osteoinduction. In vitro drug release experiments demonstrated a gentle and sustained release of SIM for as long as 2 months, benefitting bone regeneration. The excellent capacity of promoting the formation of osteocytes was proved by cell differentiation assays. Furthermore, the enhanced bone regeneration capacity was verified by the micro-CT results of rat cranial defects with implantation time. Based on our results, the organic-inorganic composite integrates the advantages of each component and is far beyond, thus it might serve as a promising material candidate for bone regeneration.

Dynamically Resettable Electrode-Electrolyte Interface through Supramolecular Sol-Gel Transition Electrolyte for Flexible Zinc Batteries.

Flexible batteries based on gel electrolytes with high safety are promising power solutions for wearable electronics but suffer from vulnerable electrode-electrolyte interfaces especially upon complex deformations, leading to irreversible capacity loss or even battery collapse. Here, a supramolecular sol-gel transition electrolyte (SGTE) that can dynamically accommodate deformations and repair electrode-electrolyte interfaces through its controllable rewetting at low temperatures is designed. Mediated by the micellization of polypropylene oxide blocks in Pluronic and host-guest interactions between α-cyclodextrin (α-CD) and polyethylene oxide blocks, the high ionic conductivity and compatibility with various salts of SGTE afford resettable electrode-electrolyte interfaces and thus constructions of a series of highly durable, flexible aqueous zinc batteries. The design of this novel gel electrolyte provides new insights for the development of flexible batteries.

Core-Shell Gyroid in ABC Bottlebrush Block Terpolymers.

Block polymer self-assembly provides a versatile platform for creating useful materials endowed with three-dimensional periodic network morphologies that support orthogonal physical properties such as high ionic conductivity and a high elastic modulus. However, coil configurations limit conventional linear block polymers to finite ordered network dimensions, which are further restricted by slow self-assembly kinetics at high molecular weights. A bottlebrush architecture can circumvent both shortcomings owing to extended backbone configurations due to side chain crowding and molecular dynamics substantially free of chain entanglements. However, until now, network morphologies have not been reported in AB bottlebrush block copolymers, notwithstanding favorable mean-field predictions. We explored the phase behavior by small-angle X-ray scattering of 133 poly(ethylene-alt-propylene)-b-polystyrene (PEP-PS) diblock and PEP-PS-PEO triblock bottlebrush copolymers prepared by ring-opening metathesis polymerization (ROMP) of norbornene-functionalized poly(ethylene-alt-propylene) (PEP), poly(styrene) (PS), and poly(ethylene oxide) (PEO) macromonomers with total backbone degrees of polymerization Nbb between 20 and 40. The PEP-PS diblocks exhibited only cylindrical and lamellar morphologies over the composition range of ca. 30-70%. However, addition of variable-length bottlebrush PEO blocks to diblocks containing 30-50% PS led to the formation of a substantial core-shell double gyroid (GYR) phase window containing 20 bottlebrush triblock specimens, which is the focus of this report. Encouragingly, the GYR unit cell dimensions increased as d ∼ Nbb0.92, portending the ability to access larger network dimensions than previously obtained with linear AB or ABC block polymers. This work highlights extraordinary opportunities associated with applying facile ROMP chemistry to multiblock bottlebrush polymers.

Injectable Thermogel Generated by the "Block Blend" Strategy as a Biomaterial for Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection is an established method for the removal of early cancers and large lesions from the gastrointestinal tract but is faced with the risk of perforation. To decrease this risk, a submucosal fluid cushion (SFC) is needed clinically by submucosal injection of saline and so on to lift and separate the lesion from the muscular layer. Some materials have been tried as the SFC so far with disadvantages. Here, we proposed a thermogel generated by the "block blend" strategy as an SFC. This system was composed of two amphiphilic block copolymers in water, so it was called a "block blend". We synthesized two non-thermogellable copolymers poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) and blended them in water to achieve a sol-gel transition upon heating in both pure water and physiological saline. We explored the internal structure of the resultant thermogel with transmission electron microscopy, three-dimensional light scattering, 13C NMR, fluorescence resonance energy transfer, and rheological measurements, which indicated a percolated micelle network. The biosafety of the synthesized copolymer was preliminarily confirmed in vitro. The main necessary functions as an SFC, namely, injectability of a sol and the maintained mucosal elevation as a gel after injection, were verified ex vivo. This study has revealed the internal structure of the block blend thermogel and illustrated its potential application as a biomaterial. This work might be stimulating for investigations and applications of intelligent materials with both injectability and thermogellability of tunable phase-transition temperatures.

Cell-Free Bilayered Porous Scaffolds for Osteochondral Regeneration Fabricated by Continuous 3D-Printing Using Nascent Physical Hydrogel as Ink.

Cartilage is difficult to self-repair and it is more challenging to repair an osteochondral defects concerning both cartilage and subchondral bone. Herein, it is hypothesized that a bilayered porous scaffold composed of a biomimetic gelatin hydrogel may, despite no external seeding cells, induce osteochondral regeneration in vivo after being implanted into mammal joints. This idea is confirmed based on the successful continuous 3D-printing of the bilayered scaffolds combined with the sol-gel transition of the aqueous solution of a gelatin derivative (physical gelation) and photocrosslinking of the gelatin methacryloyl (gelMA) macromonomers (chemical gelation). At the direct printing step, a nascent physical hydrogel is extruded, taking advantage of non-Newtonian and thermoresponsive rheological properties of this 3D-printing ink. In particular, a series of crosslinked gelMA (GelMA) and GelMA-hydroxyapatite bilayered hydrogel scaffolds are fabricated to evaluate the influence of the spacing of 3D-printed filaments on osteochondral regeneration in a rabbit model. The moderately spaced scaffolds output excellent regeneration of cartilage with cartilaginous lacunae and formation of subchondral bone. Thus, tricky rheological behaviors of soft matter can be employed to improve 3D-printing, and the bilayered hybrid scaffold resulting from the continuous 3D-printing is promising as a biomaterial to regenerate articular cartilage.

Cell migration regulated by RGD nanospacing and enhanced under moderate cell adhesion on biomaterials.

While nanoscale modification of a biomaterial surface is known to influence various cell behaviors, it is unclear whether there is an optimal nanospacing of a bioactive ligand with respect to cell migration. Herein, we investigated the effects of nanospacing of arginine-glycine-aspartate (RGD) peptide on cell migration and its relation to cell adhesion. To this end, we prepared RGD nanopatterns with varied nanospacings (31-125 nm) against the nonfouling background of poly(ethylene glycol), and employed human umbilical vein endothelial cells (HUVECs) to examine cell behaviors on the nanopatterned surfaces. While HUVECs adhered well on surfaces of RGD nanospacing less than 70 nm and exhibited a monotonic decrease of adhesion with the increase of RGD nanospacing, cell migration exhibited a nonmonotonic change with the ligand nanospacing: the maximum migration velocity was observed around 90 nm of nanospacing, and slow or very slow migration occurred in the cases of small or large RGD nanospacings. Therefore, moderate cell adhesion is beneficial for fast cell migration. Further molecular biology studies revealed that attenuated cell adhesion and activated dynamic actin rearrangement accounted for the promotion of cell migration, and the genes of small G proteins such as Cdc42 were upregulated correspondingly. The present study sheds new light on cell migration and its relation to cell adhesion, and paves a way for designing biomaterials for applications in regenerative medicine.

Structural mechanics of 3D-printed poly(lactic acid) scaffolds with tetragonal, hexagonal and wheel-like designs.

While various porous scaffolds have been developed, the focused study about which structure leads to better mechanics is rare. In this study, we designed porous scaffolds with tetragonal, hexagonal and wheel-like structures under a given porosity, and fabricated corresponding poly(lactic acid) (PLA) scaffolds with three-dimensional printing. High-resolution micro-computed tomography was carried out to calculate their experimental porosity and confirm their high interconnectivity. The theoretical and experimental compressive properties in the longitudinal direction were characterized by finite element analysis method and electromechanical universal testing system, respectively. Thereinto, the scaffold with the tetragonal structure exhibited higher mechanical strength both theoretically and experimentally. Creep and stress relaxation behaviors of the scaffolds revealed that the tetragonal scaffold had less significant viscoelasticity. Immersion dynamic mechanical analysis was performed to test their cycle-loading fatigue behaviors in the simulated body fluid at 37 °C; the tetragonal scaffold exhibited the latest fatigue beginning point at 4400 cycles, which indicated a better anti-fatigue performance; the hexagonal and wheel-like ones exhibited the middle and earliest fatigue beginning points at 3200 and 2500 cycles, respectively. What is more, cytocompatibility and histocompatibility of the scaffolds with all of the structures were confirmed by cell counting kit-8 assay in vitro and three-month subcutaneous implantation in rats in vivo. Hence, the key property difference of the three examined structures comes from their mechanics; the tetragonal structure exhibited better mechanics in the longitudinal direction examined in this study, which could be taken into consideration in design of a porous scaffold for tissue engineering and regeneration.

Strategy of Metal-Polymer Composite Stent To Accelerate Biodegradation of Iron-Based Biomaterials.

The new principle and technique to tune biodegradation rates of biomaterials is one of the keys to the development of regenerative medicine and next-generation biomaterials. Biodegradable stents are new-generation medical devices applied in percutaneous coronary intervention, etc. Recently, both corrodible metals and degradable polymers have drawn much attention in biodegradable stents or scaffolds. It is, however, a dilemma to achieve good mechanical properties and appropriate degradation profiles. Herein, we put forward a metal-polymer composite strategy to achieve both. Iron stents exhibit excellent mechanical properties but low corrosion rate in vivo. We hypothesized that coating of biodegradable aliphatic polyester could accelerate iron corrosion due to the acidic degradation products, etc. To demonstrate the feasibility of this composite material technique, we first conducted in vitro experiments to affirm that iron sheet corroded faster when covered by polylactide (PLA) coating. Then, we fabricated three-dimensional metal-polymer stents (MPS) and implanted the novel stents in the abdominal aorta of New Zealand white rabbits, setting metal-based stents (MBS) as a control. A series of in vivo experiments were performed, including measurements of residual mass and radial strength of the stents, histological analysis, micro-computed tomography, and optical coherence tomography imaging at the implantation site. The results showed that MPS could totally corrode in some cases, whereas iron struts of MBS in all cases remained several months after implantation. Corrosion rates of MPS could be easily regulated by adjusting the composition of PLA coatings.

Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization.

Inadequate drug loading of hydrophobic drugs is a classic problem when hydrogels are utilized as sustained-release carriers of drugs. Herein, a strategy to load plenty of hydrophobic drugs is presented. The antitumor drug 10-hydroxycamptothecin in the thermogel of poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) is employed. The drug is soluble in an alkaline medium, yet insoluble in a neutral/acidic medium. The crystallization is triggered after adding an alkaline drug solution into an acidic copolymer solution. The concentrated copolymer aqueous solution undergoes a sol-gel transition upon heating, faster than the crystallization. As a result, plenty of evenly dispersed drug microcrystals are formed. The in vitro and in vivo experiments indicate both high drug loading and sustained release with enhanced antitumor efficacy and reduced adverse effects. The system resolves the challenge in formulation of hydrophobic drugs in hydrogels, and is stimulating for encapsulating drugs with a soluble-insoluble transition into a material environment.