A comparison of accuracy among different approaches of static-guided implant placement in patients treated with mandibular reconstruction: A retrospective study.

OBJECTIVE: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction. METHODS: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation. RESULTS: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation. CONCLUSION: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction.

Gradient Functionalization of Various Quaternized Polyethylenimines on Microfluidic Chips for the Rapid Appraisal of Antibacterial Potencies.

The ability to appraise antibacterial potencies of surface-immobilized bactericidal polymers is still a major challenge in the engineering of antibacterial surfaces to combat hospital-acquired (nosocomial) infections. In this work, we fabricated a microfluidic platform with gradiently immobilized bactericidal polymers to enable the rapid appraisal of antibacterial potencies by in situ live/dead staining of bacteria. To this end, a variety of synthetic quaternary polymers, named QPEI-C1, QPEI-C6, QPEI-C8, and QPEI-C10, were gradiently immobilized in microfluidic channels, and their surface densities at different distances along the channels were quantified by using fluorescein-labeled polymers. We found that the surface densities of quaternary polymers could be well-tuned, and the length of the channel, resulting in a 50% reduction of live bacteria (L50), can be used to appraise the antibacterial potency of each bactericidal polymer. For instance, the L50 values of QPEI-C6-, QPEI-C8-, and QPEI-C10-modified channels against Escherichia coli were 35.5, 44.7, and 49.2 mm, respectively, indicating that QPEI-C10 exerted the most potent antibacterial efficacy. More importantly, this microfluidic platform enabled the rapid discrimination of antibacterial potencies of polymers (e.g., QPEI-C8, and QPEI-C10) while the conventional live/dead staining method found no significant difference. This work provides a powerful toolkit by combining advances of microfluidic systems and polymer science for the rapid screening of antibacterial coatings, which would find applications in surface modification of medical devices to combat bacterial infections.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug-Resistant Bacteria.

The human society is faced with daunting threats from bacterial infections. Over decades, a variety of antibacterial polymeric nanosystems have exhibited great promise for the eradication of multidrug-resistant bacteria and persistent biofilms by enhancing bacterial recognition and binding capabilities. In this Review, the "state-of-the-art" biodegradable antibacterial polymeric nanosystems, which could respond to bacteria environments (e.g., acidity or bacterial enzymes) for controlled antibiotic release or multimodal antibacterial treatment, are summarized. The current antibacterial polymeric nanosystems can be categorized into antibiotic-containing and intrinsic antibacterial nanosystems. The antibiotic-containing polymeric nanosystems include antibiotic-encapsulated nanocarriers (e.g., polymeric micelles, vesicles, nanogels) and antibiotic-conjugated polymer nanosystems for the delivery of antibiotic drugs. On the other hand, the intrinsic antibacterial polymer nanosystems containing bactericidal moieties such as quaternary ammonium groups, phosphonium groups, polycations, antimicrobial peptides (AMPs), and their synthetic mimics, are also described. The biodegradability of the nanosystems can be rendered by the incorporation of labile chemical linkages, such as carbonate, ester, amide, and phosphoester bonds. The design and synthesis of the degradable polymeric building blocks and their fabrications into nanosystems are also explicated, together with their plausible action mechanisms and potential biomedical applications. The perspectives of the current research in this field are also described.

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Cationic Polymer-Mediated CRISPR/Cas9 Plasmid Delivery for Genome Editing.

Delivery of CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein-9 (Cas9) represents a major hurdle for successful clinical translation of genome editing tools. Owing to the large size of plasmids that encode Cas9 and single-guide RNA (sgRNA), genome editing efficiency mediated by current delivery carriers is still unsatisfactory to meet the requirement for its real applications. Herein, cationic polymer polyethyleneimine-ß-cyclodextrin (PC), known to be efficient for small plasmid transfection, is reported to likewise mediate efficient delivery of plasmid encoding Cas9 and sgRNA. Whereas PC can condense and encapsulate large plasmids at high N/P ratio, the delivery of plasmid results in efficient editing at two genome loci, namely, hemoglobin subunit beta (19.1%) and rhomboid 5 homolog 1 (RHBDF1) (7.0%). Sanger sequencing further confirms the successful genome editing at these loci. This study defines a new strategy for the delivery of the large plasmid encoding Cas9/sgRNA for efficient genome editing.

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications.

One challenge for multimodal therapy is to develop appropriate multifunctional agents to meet the requirements of potential applications. Photodynamic therapy (PDT) is proven to be an effective way to treat cancers. Diverse polycations, such as ethylenediamine-functionalized poly(glycidyl methacrylate) (PGED) with plentiful primary amines, secondary amines, and hydroxyl groups, demonstrate good gene transfection performances. Herein, a series of multifunctional cationic nanoparticles (PRP) consisting of photosensitizer cores and PGED shells are readily developed through simple dopamine-involving processes for versatile bioapplications. A series of experiments demonstrates that PRP nanoparticles are able to effectively mediate gene delivery in different cell lines. PRP nanoparticles are further validated to possess remarkable capability of combined PDT and gene therapy for complementary tumor treatment. In addition, because of their high dispersities in biological matrix, the PRP nanoparticles can also be used for in vitro and in vivo imaging with minimal aggregation-caused quenching. Therefore, such flexible nanoplatforms with photosensitizer cores and polycationic shells are very promising for multimodal tumor therapy with high efficacy.

Versatile Functionalization of Polysaccharides via Polymer Grafts: From Design to Biomedical Applications.

Because of their biocompatibility, biodegradability, and unique bioactive properties, polysaccharides have been recognized and directly applied as excellent candidates for various biomedical applications. In order to introduce more functionalities onto polysaccharides, various modification methods were applied to improve the physical-chemical and biochemical properties. Grafting polysaccharides with functional polymers with limited reaction sites maximizes the structural integrity. To the best of our knowledge, great efforts have been made by scientists across the world, including our research group, to explore different strategies for the synthesis and design of controllable polymer-grafted polysaccharides. By the application of some reasonable strategies, a series of polymer-grafted polysaccharides with satisfactory biocharacteristics were obtained. The first strategy involves facile modification of polysaccharides with living radical polymerization (LRP). Functionalized polysaccharides with diverse grafts can be flexibly and effectively achieved. The introduced grafts include cationic components for nuclei acid delivery, PEGylated and zwitterionic moieties for shielding effects, and functional species for bioimaging applications as well as bioresponsive drug release applications. The second synthetic model refers to biodegradable polymer-grafted polysaccharides prepared by ring-opening polymerization (ROP). Inspired by pathways to introduce initiation sites onto polysaccharides, the use of amine-functionalized polysaccharides was explored in-depth to trigger ROP of amino acids. A series of poly(amino acid)-grafted polysaccharides with advanced structures (including linear, star-shaped, and comb-shaped copolymers) were developed to study and optimize the structural effects. In addition, biodegradable polyester-grafted polysaccharides were prepared and utilized for drug delivery. Another emerging strategy was to design polysaccharide-based assemblies with supramolecular structures. A variety of assembly techniques using non-covalent interactions were established to construct different types of polysaccharide-based assemblies with various bioapplications. On the basis of these strategies, polymer-grafted polysaccharides with controllable functions were reported to be well-suited for different kinds of biomedical applications. The exciting results were obtained from both in vitro and in vivo models. Viewing the rapid growth of this field, the present Account will update the concepts, trends, perspectives, and applications of functionalized polysaccharides, guiding and inspiring researchers to explore new polysaccharide-based systems for wider applications.

Series of In Situ Photoinduced Polymer Graftings for Sensitive Detection of Protein Biomarkers via Cascade Amplification of Liquid Crystal Signals.

Developing of new polymeric materials for the sensitive and rapid detection of trace protein biomarkers has attracted increasing attention in biomedical fields. Herein, series of in situ photoinduced polymer graftings were developed for sensitive detection of protein biomarkers by using featured cascade amplification of liquid crystal (LC) signals. The limit-of-detection (LOD) for native bovine serum albumin (BSA) molecules is around 10 µg/mL in a LC biosensor before signal amplification. Upon the cascade amplification using surface-grafted polymers, poly[poly(ethylene glycol) methacrylate] grafting ( s-P(PEGMA)) exhibits superior amplification ability (104-fold lower than native BSA) than the other two graftings of poly(2-hydroxyethyl methacrylate) ( s-PHEMA) and poly(methacrylic acid) ( s-PMAA; 102-fold lower than native BSA). The contact angles of water and LC on the s-P(PEGMA) grafting show significant difference in comparison with s-PHEMA and s-PMAA graftings ( p < 0.05), implying interfacial energies of the grafted polymers may dictate the orientational transition of LCs. The clinical urine samples collected from the patients with proteinuria were also used to confirm the feasibility of the polymer-amplified LC sensors for practical protein assays. The present work reveals that in situ photoinduced polymer grafting is one promising method to amplify the signals of LC biosensors for the rapid and sensitive detection of trace protein biomarkers.

Antimicrobial and Antifouling Polymeric Agents for Surface Functionalization of Medical Implants.

Combating implant-associated infections is an urgent demand due to the increasing numbers in surgical operations such as joint replacements and dental implantations. Surface functionalization of implantable medical devices with polymeric antimicrobial and antifouling agents is an efficient strategy to prevent bacterial fouling and associated infections. In this work, antimicrobial and antifouling branched polymeric agents (GPEG and GEG) were synthesized via ring-opening reaction involving gentamicin and ethylene glycol species. Due to their rich primary amine groups, they can be readily coated on the polydopamine-modified implant (such as titanium) surfaces. The resultant surface coatings of Ti-GPEG and Ti-GEG produce excellent in vitro antibacterial efficacy toward both Staphylococcus aureus and Escherichia coli, while Ti-GPEG exhibit better antifouling ability. Moreover, the infection model with S. aureus shows that implanted Ti-GPEG possessed excellent antibacterial and antifouling ability in vivo. This study would provide a promising strategy for the surface functionalization of implantable medical devices to prevent implant-associated infections.

NIR-Responsive Polycationic Gatekeeper-Cloaked Hetero-Nanoparticles for Multimodal Imaging-Guided Triple-Combination Therapy of Cancer.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

PGMA-Based Cationic Nanoparticles with Polyhydric Iodine Units for Advanced Gene Vectors.

It is crucial for successful gene delivery to develop safe, effective, and multifunctional polycations. Iodine-based small molecules are widely used as contrast agents for CT imaging. Herein, a series of star-like poly(glycidyl methacrylate) (PGMA)-based cationic vectors (II-PGEA/II) with abundant flanking polyhydric iodine units are prepared for multifunctional gene delivery systems. The proposed II-PGEA/II star vector is composed of one iohexol intermediate (II) core and five ethanolamine (EA) and II-difunctionalized PGMA arms. The amphipathic II-PGEA/II vectors readily self-assemble into well-defined cationic nanoparticles, where massive hydroxyl groups can establish a hydration shell to stabilize the nanoparticles. The II introduction improves cell viabilities of polycations. Moreover, by controlling the suitable amount of introduced II units, the resultant II-PGEA/II nanoparticles can produce fairly good transfection performances in different cell lines. Particularly, the II-PGEA/II nanoparticles induce much better in vitro CT imaging abilities in tumor cells than iohexol (one commonly used commercial CT contrast agent). The present design of amphipathic PGMA-based nanoparticles with CT contrast agents would provide useful information for the development of new multifunctional gene delivery systems.

Redox-Triggered Gatekeeper-Enveloped Starlike Hollow Silica Nanoparticles for Intelligent Delivery Systems.

The design and development of multifunctional carriers for drug delivery based on hollow nanoparticles (HNPs) have attracted intense interests. Ordinary spherical HNPs are demonstrated to be promising candidates. However, the application of HNPs with special morphologies has rarely been reported. HNPs with sharp horns are expected to own higher endocytosis efficiencies than spherical counterparts. In this work, novel starlike hollow silica nanoparticles (SHNPs) with different sizes are proposed as platforms for the fabrication of redox-triggered multifunctional systems for synergy of gene therapy and chemotherapy. The CD-PGEA gene vectors (consisting of ß-CD cores and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted BUCT-PGEA) arms) are introduced ingeniously onto the surfaces of SHNPs with plentiful disulfide bond-linked adamantine guests. The resulting supramolecular assemblies (SHNP-PGEAs) possess redox-responsive gatekeepers for loaded drugs in the cavities of SHNPs. Meanwhile, they also demonstrate excellent performances to deliver genes. The gene transfection efficiencies, controlled drug release behaviors, and synergistic antitumor effect of hollow silica-based carriers with different morphologies are investigated in detail. Compared with ordinary spherical HNP-based counterparts, SHNP-PGEA carriers with six sharp horns are proven to be superior gene vectors and possess better efficacy for cellular uptake and antitumor effects. The present multifunctional carriers based on SHNPs will have promising applications in drug/gene codelivery and cancer treatment.

Biomolecule-functionalized polymer brushes.

Functional polymer brushes have been utilized extensively for the immobilization of biomolecules, which is of crucial importance for the development of biosensors and biotechnology. Recent progress in polymerization methods, in particular surface-initiated atom transfer radical polymerization (ATRP), has provided a unique means for the design and synthesis of new biomolecule-functionalized polymer brushes. This current review summarizes such recent research activities. The different preparation strategies for biomolecule immobilization through polymer brush spacers are described in detail. The functional groups of the polymer brushes used for biomolecule immobilization include epoxide, carboxylic acid, hydroxyl, aldehyde, and amine groups. The recent research activities indicate that functional polymer brushes become versatile and powerful spacers for immobilization of various biomolecules to maximize their functionalities. This review also demonstrates that surface-initiated ATRP is used more frequently than other polymerization methods in the designs of new biomolecule-functionalized polymer brushes.

A Janus Gelatin Sponge with a Procoagulant Nanoparticle-Embedded Surface for Coagulopathic Hemostasis.

Apart from the wide and safe application of natural polymer-based hemostatic materials/devices, it is still desirable to develop new types of hemostatic materials that can achieve both potent coagulopathic hemostasis and a facile preparation process. In this work, one Janus gelatin sponge (J-ZGS) is readily constructed for both coagulation-dependent and coagulopathic hemostasis by embedding zein nanoparticles on the surface of a self-prepared gelatin sponge (S-GS): zein nanoparticles were facilely prepared by an antisolvent method to achieve procoagulant blood-material interactions, while S-GS was prepared by freeze-drying a foaming gelatin solution. Due to the distinct secondary structure, the optimal zein nanoparticles possessed a higher in vitro hemostatic property than the pristine zein powder and other nanoparticles, the underlying mechanism of which was revealed as the superior RBC/platelet adhesion property in the presence/absence of plasma proteins. Compared with S-GS and a commercial gelatin sponge, J-ZGS achieved a significantly higher in vitro hemostatic property and similarly good blood compatibility/cytocompatibility. Moreover, in vivo artery-injury models confirmed the outstanding hemostatic performance of J-ZGS under both coagulation-dependent and coagulopathic conditions. Our work offers an appealing approach for developing potent hemostatic sponges from natural polymer-based nanoparticles that could be further extended to versatile hemostatic materials for coagulopathic hemostasis.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

Rough Nanovaccines Boost Antitumor Immunity Through the Enhancement of Vaccination Cascade and Immunogenic Cell Death Induction.

Nanovaccines have attracted intense interests for efficient antigen delivery and tumor-specific immunity. It is challenging to develop a more efficient and personalized nanovaccine to maximize all steps of the vaccination cascade by exploiting the intrinsic properties of nanoparticles. Here, biodegradable nanohybrids (MP) composed of manganese oxide nanoparticles and cationic polymers are synthesized to load a model antigen ovalbumin to form MPO nanovaccines. More interestingly, MPO could serve as autologous nanovaccines for personalized tumor treatment taking advantage of in situ released tumor-associated antigens induced by immunogenic cell death (ICD). The intrinsic properties of MP nanohybrids including morphology, size, surface charge, chemical, and immunoregulatory functions are fully exploited to enhance of all steps of the cascade and induce ICD. MP nanohybrids are designed to efficiently encapsulate antigens by cationic polymers, drain to lymph nodes by appropriate size, be internalized by dendritic cells (DCs) by rough morphology, induce DC maturation through cGAS-STING pathway, and enhance lysosomal escape and antigen cross-presentation through the "proton sponge effect". The MPO nanovaccines are found to efficiently accumulate in lymph nodes and elicit robust specific T-cell immune responses to inhibit the occurrence of ovalbumin-expressing B16-OVA melanoma. Furthermore, MPO demonstrate great potential to serve as personalized cancer vaccines through the generation of autologous antigen depot through ICD induction, activation of potent antitumor immunity, and reversal of immunosuppression. This work provides a facile strategy for the construction of personalized nanovaccines by exploiting the intrinsic properties of nanohybrids.

BODIPY-Functionalized Natural Polymer Coatings for Multimodal Therapy of Drug-Resistant Bacterial Infection.

The fact that multidrug resistance (MDR) could induce medical device-related infections, along with the invalidation of traditional antibiotics has become an intractable global medical issue. Therefore, there is a pressing need for innovative strategies of antibacterial functionalization of medical devices. For this purpose, a multimodal antibacterial coating that combines photothermal and photodynamic therapies (PTT/PDT) is developed here based on novel heavy atom-free photosensitizer compound, BDP-6 (a kind of boron-dipyrromethene). The photothermal conversion efficiency of BDP-6 is of 55.9%, which could improve biocompatibility during PTT/PDT process by reducing the exciting light power density. Furthermore, BDP-6, together with oxidized hyaluronic acid, is crosslinked with a natural polymer, gelatin, to fabricate a uniform coating (denoted as polyurethane (PU)-GHB) on the surface of polyurethane. PU-GHB has excellent synergistic in vitro PTT/PDT antibacterial performance against both susceptible bacteria and MDR bacteria. The antibacterial mechanisms are revealed as that hyperthermia could reduce the bacterial activity and enhance the permeability of inner membrane to reactive oxygen species by disturbing cell membrane. Meanwhile, in an infected abdominal wall hernia model, the notable anti-infection performance, good in vivo compatibility, and photoacoustic imaging property of PU-GHB are verified. A promising strategy of developing multifunctional antibacterial coatings on implanted medical devices is provided here.

A natural polyphenol-functionalized chitosan/gelatin sponge for accelerating hemostasis and infected wound healing.

Natural polymers have been particularly appealing for constructing hemostatic materials/devices, but it is still desirable to develop new natural polymer-based biomaterials with balanced hemostatic and wound-healing performance. In this work, a natural polyphenol-functionalized chitosan/gelatin sponge (PCGS) was prepared by the lyophilization of a chitosan/gelatin mixture solution (under a self-foaming condition to prepare the CGS) and subsequent chemical cross-linking with procyanidin (PC). Compared with the original CGS, PCGS exhibited an enhanced liquid-absorption ability, reduced surface charges, and similar/low hemolysis rate. Benefiting from such a liquid-absorption ability (∼4000% for whole blood and normal saline) and moderate surface charges, PCGS exhibited high in vitro hemostatic property and promising hemostatic performance in an in vivo femoral-artery-injury model. In addition, PCGS possessed higher antioxidant property and slightly decreased antibacterial ability than CGS, owing to the incorporation of PC. The feasibility of PCGS for treating infected wounds was further confirmed in an in vivo infected-tooth-extraction model, as the typical complication of intractable tooth-extraction bleeding. The present work demonstrated a facile approach for developing multifunctional hemostatic materials through the flexible management of natural polymers and polyphenols.

Fluorination of Polyethylenimines for Augmentation of Antibacterial Potency via Structural Damage and Potential Dissipation of Bacterial Membranes.

The rise of drug-resistant bacteria (e.g., methicillin-resistant Staphylococcus aureus, MRSA) has continued, making the ″super-bugs″ a formidable threat to global health. Herein, we synthesize a series of fluoroalkylated polyethylenimines (PEI-F) with different grafting degrees of fluoroalkyls via a simple ring-opening reaction and demonstrate for the first time that fluoroalkylated PEIs are able to exert potent antibacterial activity to Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Among the fluoroalkylated polymers, PEI-F3.0 shows the strongest antibacterial activity, with a minimum inhibitory concentration (MIC) of 64 µg mL-1, against both E. coli and S. aureus. More importantly, we find that PEI-F3.0 is able to kill over 99.8% of S. aureus within 1 min, which is extremely desirable for the treatment of acute and severe bacterial infections that require quick disinfection. We also demonstrate that the fluoroalkylated PEIs are able to kill bacteria via structural damage of the outer membrane (OM) and cytoplasmic membrane (CM), potential dissipation of CM, and generation of intracellular reactive oxygen species (ROS). The in vivo antibacterial test suggests that commercial Vaseline blended with 6.25 wt % of PEI-F3.0 (VL/PEI-F3.0) is able to efficaciously eradicate MRSA infection on a bacterial infected wound model and promote the healing procedure of the wound site. Therefore, the fluoroalkylated PEIs provide a promising strategy to cope with the major challenges of drug-resistant infections.