Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

Robust, Sprayable, and Multifunctional Hydrogel Coating through a Polycation Reinforced (PCR) Surface Bridging Strategy.

The sprayable hydrogel coatings that can establish robust adhesion onto diverse materials and devices hold enormous potential; however, a significant challenge persists due to monomer hydration, which impedes even coverage during spraying and induces inadequate adhesion post-gelation. Herein, a polycation-reinforced (PCR) surface bridging strategy is presented to achieve tough and sprayable hydrogel coatings onto diverse materials. The polycations offer superior wettability and instant electrostatic interactions with plasma-treated substrates, facilitating an effective spraying application. This PCR-based hydrogel coatings demonstrate tough adhesion performance to inert PTFE and silicone, including remarkable shear strength (161 ± 49 kPa for PTFE), interfacial toughness (198 ± 27 J m-2 for PTFE), and notable tolerance to cyclic tension (10 000 cycles, 200% strain, silicone). Meanwhile, this method can be applied to various hydrogel formulations, offering diverse functionalities, including underwater adhesion, lubrication, and drug delivery. Furthermore, the PCR concept enables the conformal construction of durable hydrogel coatings onto sophisticated medical devices like cardiovascular stents. Given its simplicity and adaptability, this approach paves an avenue for incorporating hydrogels onto solid surfaces and potentially promotes untapped applications.

"Spongy skin" as a robust strategy to deliver 4-octyl itaconate for conducting dual-regulation against in-stent restenosis.

The valid management of inflammation and precise inhibition of smooth muscle cells (SMCs) is regarded as a promising strategy for regulating vascular responses after stent implantation, yet posing huge challenges to current coating constructions. Herein, we proposed a spongy cardiovascular stent for the protective delivery of 4-octyl itaconate (OI) based on a "spongy skin" approach, and revealed the dual-regulation effects of OI for improving vascular remolding. We first constructed a "spongy skin" onto poly-l-lactic acid (PLLA) substrates, and realized the protective loading of OI with the highest dosage of 47.9 µg/cm2. Then, we verified the remarkable inflammation mediation of OI, and surprisingly revealed that the OI incorporation specifically inhibited SMC proliferation and phenotype switching, which contributed to the competitive growth of endothelial cells (EC/SMC ratio âˆ¼ 5.1). We further demonstrated that OI at a concentration of 25 µg/mL showed significant suppression of the TGF-ß/Smad pathway of SMCs, leading to the promotion of contractile phenotype and reduction of extracellular matrix. In vivo evaluation indicated that the successful delivery of OI fulfilled the inflammation regulation and SMCs inhibition, therefore suppressing the in-stent restenosis. This "spongy skin" based OI eluting system may serve as a new strategy for improving vascular remolding, and provides a potential concept for the treatment of cardiovascular diseases.

A deep-learning-based workflow to deal with the defocusing problem in high-throughput experiments.

The increasing throughput of experiments in biomaterials research makes automatic techniques more and more necessary. Among all the characterization methods, microscopy makes fundamental contributions to biomaterials science where precisely focused images are the basis of related research. Although automatic focusing has been widely applied in all kinds of microscopes, defocused images can still be acquired now and then due to factors including background noises of materials and mechanical errors. Herein, we present a deep-learning-based method for the automatic sorting and reconstruction of defocused cell images. First, the defocusing problem is illustrated on a high-throughput cell microarray. Then, a comprehensive dataset of phase-contrast images captured from varied conditions containing multiple cell types, magnifications, and substrate materials is prepared to establish and test our method. We obtain high accuracy of over 0.993 on the dataset using a simple network architecture that requires less than half of the training time compared with the classical ResNetV2 architecture. Moreover, the subcellular-level reconstruction of heavily defocused cell images is achieved with another architecture. The applicability of the established workflow in practice is finally demonstrated on the high-throughput cell microarray. The intelligent workflow does not require a priori knowledge of focusing algorithms, possessing widespread application value in cell experiments concerning high-throughput or time-lapse imaging.

Fabrication of "Spongy Skin" on Diversified Materials Based on Surface Swelling Non-Solvent-Induced Phase Separation.

Porous surfaces have attracted tremendous interest for customized incorporation of functional agents on biomedical devices. However, the versatile preparation of porous structures on complicated devices remains challenging. Herein, we proposed a simple and robust method to fabricate "spongy skin" on diversified polymeric substrates based on non-solvent-induced phase separation (NIPS). Through the swelling and the subsequent phase separation process, interconnected porous structures were directly formed onto the polymeric substrates. The thickness and pore size could be regulated in the ranges of 5-200 and 0.3-0.75 µm, respectively. The fast capillary action of the porous structure enabled controllable loading and sustained release of ofloxacin and bovine albumin at a high loading dosage of 79.9 and 24.1 µg/cm2, respectively. We verified that this method was applicable to diversified materials including polymethyl methacrylate, polystyrene, thermoplastic polyurethane, polylactide acid, and poly(lactic-co-glycolic acid) and can be realized onto TCPS cell culture plates. This NIPS-based method is promising to generate porous surfaces on medical devices for incorporating therapeutic agents.

miR-22 eluting cardiovascular stent based on a self-healable spongy coating inhibits in-stent restenosis.

The in-stent restenosis (IRS) after the percutaneous coronary intervention contributes to the major treatment failure of stent implantation. MicroRNAs have been revealed as powerful gene medicine to regulate endothelial cells (EC) and smooth muscle cells (SMC) in response to vascular injury, providing a promising therapeutic candidate to inhibit IRS. However, the controllable loading and eluting of hydrophilic bioactive microRNAs pose a challenge to current lipophilic stent coatings. Here, we developed a microRNA eluting cardiovascular stent via the self-healing encapsulation process based on an amphipathic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) triblock copolymer spongy network. The miR-22 was used as a model microRNA to regulate SMC. The dynamic porous coating realized the uniform and controllable loading of miR-22, reaching the highest dosage of 133 pmol cm-2. We demonstrated that the sustained release of miR-22 dramatically enhanced the contractile phenotype of SMC without interfering with the proliferation of EC, thus leading to the EC dominating growth at an EC/SMC ratio of 5.4. More importantly, the PCEC@miR-22 coated stents showed reduced inflammation, low switching of SMC phenotype, and low secretion of extracellular matrix, which significantly inhibited IRS. This work provides a simple and robust coating platform for the delivery of microRNAs on cardiovascular stent, which may extend to other combination medical devices, and facilitate practical application of bioactive agents in clinics.

Periodic Stratified Porous Structures in Dynamic Polyelectrolyte Films Through Standing-Wave Optical Crosslinking for Structural Color.

Periodic porous structures have been introduced into functional films to meet the requirements of various applications. Though many approaches have been developed to generate desired structures in polymeric films, few of them can effectively and dynamically achieve periodic porous structures. Here, a facile way is proposed to introduce periodic stratified porous structures into polyelectrolyte films. A photo-crosslinkable polyelectrolyte film of poly(ethylenimine) (PEI) and photoreactive poly(acrylic acid) derivative (PAA-N3 ) is prepared by layer-by-layer (LbL) self-assembly. Stratified crosslinking of the PEI/PAA-N3 film is generated basing on standing-wave optics. The periodic stratified porous structure is constructed by forming pores in noncrosslinked regions in the film. Thanks to the dynamic mobility of polyelectrolytes, this structural controlment can be repeated several times. The size of pores corresponding to the layer spacing of the film contributes to the structural colors. Furthermore, structural color patterns are fabricated in the film by selective photo-crosslinking using photomasks. Although the large-scale structural controlment in thick (micron-scale and above) films needs to be explored further, this work highlights the periodic structural controlment in polymeric films and thus presents an approach for application potentials in sensor, detection, and ink-free printing.

Dynamic Porous Pattern through Controlling Noncovalent Interactions in Polyelectrolyte Film for Sequential and Regional Encapsulation.

Inspired by nature, many functional surfaces have been developed with special structures in biology, chemistry, and materials. Many research studies have been focused on the preparation of surfaces with static structure. Achieving dynamical manipulation of surface structure is desired but still a great challenge. Herein, a polyelectrolyte film capable of regional and reversible changes in the microporous structure is presented. Our proposal is based on the combination of azobenzene (Azo) π-π stacking and electrostatic interaction, which could be affected respectively by ultraviolet (UV) irradiation and water plasticization, to tune the mobility of polyelectrolyte chains. The porous patterns can be obtained after regional ultraviolet irradiation and acid treatment. Owing to the reversibility of Azo π-π stacking and electrostatic interaction, the patterns can be repeatedly created and erased in the polyelectrolyte film made by layer-by-layer (LbL) self-assembly of poly(ethyleneimine)-azo and poly(acrylic acid). Furthermore, through two rounds of porous pattern formation and erasure, different functional species can be loaded separately and confined regionally within the film, showing potential applications in the functional surface. This work highlights the coordination of two noncovalent interactions in thin films for regional and reversible controlling its structure, opening a window for more in-depth development of functional surfaces.

Photothermal Spongy Film for Enhanced Surface-Mediated Transfection to Primary Cells.

Surface-mediated transfection has drawn tremendous interest for gene therapy due to its localized gene delivery characteristic and promising perspective for combination devices in clinical applications. However, a method for the controllable load of genetic agents and tunable transfection efficiency to primary cells remains unsatisfactory. Herein, we present a polymeric spongy film with modification of polydopamine (PDA) for controlling load of plasmid DNAs and improving transfection to primary endothelial cells. We demonstrate that, via wicking action, the loading of DNA into the film is simple, rapid, and highly controllable while easily reaching ∼95 µg/cm2 by only a one-shot loading process. Meanwhile, PDA endows the spongy films with a very good photothermal conversion capability. Consequently, we obtain an enhanced transfection up to ∼85% to hard-to-transfect primary endothelial cells upon NIR irradiation. Furthermore, we realize a spatial cell transfection through NIR irradiation in the defined area, suggesting a high potential for precise gene therapy. This photothermal spongy film could serve as a robust platform for surface-mediated gene therapy, and extend the paradigm of a light enhanced delivery system.