Correction: Zhu et al. Biodegradable and pH Sensitive Peptide Based Hydrogel as Controlled Release System for Antibacterial Wound Dressing Application. Molecules 2018, 23, 3383.

During the course of a review of our publication, we found two errors in Figure 4b and Figure 9 [...].

Contact/Release Coordinated Antibacterial Cotton Fabrics Coated with N-Halamine and Cationic Antibacterial Agent for Durable Bacteria-Killing Application.

Coating a cationic antibacterial layer on the surface of cotton fabric is an effective strategy to provide it with excellent antibacterial properties and to protect humans from bacterial cross-infection. However, washing with anionic detergent will inactivate the cationic antibacterial coating. Although this problem can be solved by increasing the amount of cationic antibacterial coating, excessive cationic antibacterial coating reduces the drapability of cotton fabric and affects the comfort of wearing it. In this study, a coordinated antibacterial coating strategy based on quaternary ammonium salt and a halogenated amine compound was designed. The results show that the antibacterial effect of the modified cotton fabric was significantly improved. In addition, after mechanically washing the fabric 50 times in the presence of anionic detergent, the antibacterial effect against Staphylococcus aureus and Escherichia coli was still more than 95%. Furthermore, the softness of the obtained cotton fabric showed little change compared with the untreated cotton fabric. This easy-to-implement and cost-effective approach, combined with the cationic contact and the release effect of antibacterial agents, can endow cotton textiles with durable antibacterial properties and excellent wearability.

Biodegradable and pH Sensitive Peptide Based Hydrogel as Controlled Release System for Antibacterial Wound Dressing Application.

The stimuli-sensitive and biodegradable hydrogels are promising biomaterials as controlled drug delivery systems for diverse biomedical applications. In this study, we construct hybrid hydrogels combined with peptide-based bis-acrylate and acrylic acid (AAc). The peptide-based bis-acrylate/AAc hybrid hydrogel displays an interconnected and porous structure by scanning electron microscopy (SEM) observation and exhibits pH-dependent swelling property. The biodegradation of hybrid hydrogels was characterized by SEM and weight loss, and the results showed the hydrogels have a good enzymatic biodegradation property. The mechanical and cytotoxicity properties of the hydrogels were also tested. Besides, triclosan was preloaded during the hydrogel formation for drug release and antibacterial studies. In summary, the peptide-based bis-acrylate/AAc hydrogel with stimuli sensitivity and biodegradable property may be excellent candidates as drug delivery systems for antibacterial wound dressing application.

Porphyrin and galactosyl conjugated micelles for targeting photodynamic therapy.

PURPOSE: To study the targeting and photodynamic therapy efficiency of porphyrin and galactosyl conjugated micelles based on amphiphilic copolymer galactosyl and mono-aminoporphyrin (APP) incoporated poly(2-aminoethyl methacrylate)-polycaprolactone (Gal-APP-PAEMA-PCL). METHODS: Poly(2-aminoethyl methacrylate)-polycaprolactone (PAEMA-PCL) was synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, and then Gal-APP-PAEMA-PCL was obtained after conjugation of lactobionic acid and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (APP) to PAEMA-PCL. The chemical structures of the copolymers were characterized, and their biological properties were evaluated in human laryngeal carcinoma (HEp2) and human hepatocellular liver carcinoma (HepG2) cells. RESULTS: Both APP-PAEMA-PCL and Gal-APP-PAEMA-PCL did not exhibit dark cytotoxicity to HEp2 cells and HepG2 cells. However, Gal-APP-PAEMA-PCL was taken up selectively by HepG2 cells and had the higher phototoxicity effect. Both polymers preferentially localized within cellular vesicles that correlated to the lysosomes. CONCLUSIONS: The results indicated that porphyrin and galactosyl conjugated polymer micelles exhibited higher targeting and photodynamic therapy efficacy in HepG2 cells than in HEp2 cells.

Injectable hydrogel helps bone marrow-derived mononuclear cells restore infarcted myocardium.

BACKGROUNDS: Experimental and clinical studies have suggested that cell implantation could improve cardiac function after myocardial infarction (MI). However, this technique was limited by decreased engraftment and survival of transplanted cells within the ischemic tissue. The present study was performed to investigate whether implantation of bone marrow-derived mononuclear cells (BMMNCs) encapsulated in hydrogel could increase cell engraftment and help to restore cardiac function of MI rabbits. METHODS: MI was induced in rabbits by coronary artery ligation. One week later, cell culture medium, Dex-PCL-HEMA/PNIPAAm hydrogel, BMMNCs in medium or BMMNCs in hydrogel were injected into the infarcted area of the left ventricle (LV). RESULTS: Increased cell engraftment was observed 48 h after injection when cells were encapsulated in hydrogel; 30 days after treatment, echocardiographic studies showed that injection of BMMNCs in hydrogel preserved LV ejection fraction and attenuated LV dilatation compared with other groups. Histological analysis indicated that injection of BMMNCs in hydrogel enhanced neovascular formation and prevented scar expansion compared with the other groups. CONCLUSION: Injection of hydrogel-encapsulated BMMNCs increased cell engraftment and improved LV function; this technique may serve as an effective approach to restore infarcted myocardium.

Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling.

AIMS: Myocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling. METHODS AND RESULTS: MI was induced in rabbits by coronary artery ligation; 4 days later, 200 microL Dex-PCL-HEMA/PNIPAAm gel solution was injected into the infarcted myocardium. Injection of phosphate-buffered saline served as control. Thirty days after treatment, histological analysis indicated that injection of the biomaterial prevented scar expansion and wall thinning compared with controls. Echocardiography studies showed that injection of hydrogel increased left ventricular ejection fraction and attenuated left ventricular systolic and diastolic dilatation. Haemodynamic analysis demonstrated improved cardiac function following implantation of the hydrogel. CONCLUSION: These results suggest that injection of thermosensitive Dex-PCL-HEMA/PNIPAAm hydrogel is an effective strategy that prevents adverse cardiac remodelling and dysfunction in MI rabbits.

Hydrophilic and degradable polyesters based on l-aspartic acid with antibacterial properties for potential application in hernia repair.

A polyester hernia patch has received extensive attention in mesh hernia repair. However, it is still a challenge to develop polyester-based implants with inherent antibacterial properties due to the lack of active functional groups. In this study, poly(butylene succinate-co-butylene aspartate) (PBSA) was constructed by introducing aspartic acid on a polybutylene succinate (PBS) polyester chain (PBSA). Antimicrobial treatment was conducted by grafting levofloxacin (Lv) on the surface of a PBSA polymer (PBSA-g-Lv). In vitro antibacterial test results showed that PBSA-g-Lv had sufficient local antimicrobiotic effects against Staphylococcus aureus and Escherichia coli and no side effect on L929 cells was observed. Furthermore, almost no change was observed in the thermodynamic properties of PBS and PBSA; in vivo tests demonstrated that this contact-active antibacterial PBSA-g-Lv nanofiber is a promising material to fulfill the dual functions of promoting tissue regeneration and preventing bacterial infection. The presented data confirmed that an antibiotic surface modification of PBSA polyesters was expected to be used as hernia repair materials.

Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release.

Hydrogels with pH-sensitive poly(acrylic acid) (PAAc) chains and biodegradable acryloyl-poly(-caprolactone)-2-hydroxylethyl methacrylate (AC-PCL-HEMA) chains were designed and synthesized. The morphology of hydrogel was observed by scanning electron microscopy. The degradation of the hydrogel in the presence of Pseudomonas lipase was studied. The in vitro release of bovine serum albumin from the hydrogel was investigated. Cytotoxicity study shows that the AC-PCL-HEMA/AAc copolymer exhibits good biocompatibility. Cell adhesion and migration into the hydrogel networks were evaluated by using different cell lines. The hydrogel with a lower cross-linking density and a larger pore size exhibited a better performance for cells migration.

Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study.

A multi-functional hybrid hydrogel P(M-Arg/NIPAAm) with temperature response, anti-protein adsorption and antibacterial properties was prepared and applied as wound dressing. The hydrogel was carried out by free radical copolymerization of methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm) monomers using N,N'-methylene bisacrylamide as a crosslinker, and ammonium persulfate/N,N,N', N'-tetramethylethylenediamine as the redox initiator. To endow the antimicrobial property, chlorhexidine diacetate (CHX) was preloaded into the hydrogel and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively. The antimicrobial property of two series of hydrogels was evaluated and compared. The successful synthesis of M-Arg, PHMG and hydrogels was proved by 13C NMR, 1H NMR and FTIR spectroscopy. The hydrogel morphology characterized by scanning electron microscopy confirmed that the homogeneous porous and interconnected structures of the hydrogels. The swelling, protein adsorption property, in vitro release of CHX, antimicrobial assessment, cell viability as well as in vivo wound healing in a mouse model were studied. The results showed the nontoxicity and antimicrobial P(M-Arg/NIPAAm) hydrogel accelerated the full-thickness wound healing process and had the potential application in wound dressing. STATEMENT OF SIGNIFICANCE: Despite the zwitterionic characteristic and biocompatible property of arginine based hydrogels, the brittle behavior and non-transparency still remain as a significant problem for wound dressing. Furthermore promoting the antibacterial property of the zwitterionic hydrogel is also necessary to prevent the bacterial colonization and subsequent wound infection. Therefore, we created a hybrid hydrogel combined methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm). NIPAAm improves transparency and mechanical property as well as acts as a temperature-response drug release system. Additionally, chlorhexidine (CHX) was preloaded into the hydrogels and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively, which make the hydrogel useful as a favorable antibacterial dressing. The hybrid hydrogel has a combination effect of biocompatibility, environmentally responsive transformation behavior, biodegradability, anti-protein adsorption and antimicrobial properties. This report proposes the preparation of P(M-Arg/NIPAAm) hydrogel that has a great potential for wound healing.

A rapid ammonia sensor based on lysine nanogel-sensitized PANI/PAN nanofibers.

In this paper, l-lysine-based materials which are rich in amino groups were synthesized through a chemical reaction. The polyaniline/polyacrylonitrile (PANI/PAN) thin film and PANI/PAN nanocomposite (NC) thin films doped with l-lysine based materials were obtained by electrospinning and in situ polymerization of aniline. The gas sensing properties of the PANI/PAN thin film and PANI/PAN NC thin films doped with l-lysine based materials towards NH3, ethanol, acetone, chloroform and DMF were examined at room temperature. The experimental results reveal that the PANI/PAN/l-lysine based nanogel (4-Lys-4 nanogel) NC thin film exhibited a highly selective response toward NH3 at room temperature with improved response kinetics. The PANI/PAN/4-Lys-4 nanogel NC thin film showed the response of 5.5 with response and recovery times of 22 s and 15 s, respectively, toward 100 ppm NH3, and the detection limit of 2.2 ppm. This response and recovery are quite fast compared with the reported studies based on PANI doped with other materials. The enhanced response could be attributed to the large surface area, the core-shell structure of the nanofibers and improved charge transfer as a result of a certain amount of amino groups doping PANI. Our results clearly indicate that the PANI/PAN/4-Lys-4 nanogel NC thin film could effectively be used for the practical room temperature NH3 sensing application with quite fast response and recovery properties. At the same time, a new application of 4-Lys-4 nanogel on sensors is supplied.

Novel amino acid based nanogel conjugated suture for antibacterial application.

In this study, a promising preparation strategy for antibacterial silk sutures with an l-lysine based nanogel grafting is reported. The triclosan-loaded nanogels (NGTLs) were fabricated by the convenient enzymatic degradation of macrogels, namely, triclosan-loaded macrogel, degrading into NGTLs triggered by the trypsin. Nanogels, about 60 nm and 90 nm in diameter, were obtained after 7 days of biodegradation in the enzyme solution. Triclosan maintained a sustained release period over 260 hours in trypsin solution with the concentration of 0.1 mg mL-1. Triclosan-loaded nanogel grafted silk sutures (TLNGSs) were characterized by an antibacterial activity assessment. Our results showed that TLNGS had long-term efficacy against pathogens such as S. aureus and E. coli. In particular, these TLNGSs had a relative decreased stable size of inhibition zones on agar plates in the first four days. The antibacterial activity could be sufficient evidence of the prevention of potential early wound infections. The mechanical strength tests indicated negligible influence on TLNGSs compared to commercial ones. The novel antibacterial silk sutures showed acceptable in vitro cytotoxicity according to ISO 10993-5. This novel biocompatible and biodegradable nanogel grafting to silk sutures provides an effective and universal approach for the treatment of bacterial infections.

From macro to micro to nano: the development of a novel lysine based hydrogel platform and enzyme triggered self-assembly of macro hydrogel into nanogel.

A novel l-lysine based multifunctional crosslinker family was developed and utilized to fabricate a 100% pure poly(ester amide) (PEA) hydrogel with unique structure via a novel gelation strategy in a single and rapid step. Enzyme triggered biodegradation was utilized to turn the resultant macro hydrogel into abundant microgels with a 3 micron size in the early stage. Nanogels of 50 nm in diameter were then formed after 8 days of biodegradation in the enzyme solution. The enzyme degradation of doxorubicin (DOX) loaded macro-gel indicated that the micro and nano gels containing DOX could be obtained using the same strategy while retaining their sustained drug release performance. This study reports a new biocompatible and biodegradable crosslinker and hydrogel system, and illustrates a new nanotechnology capable of controllably producing nanogels using the enzymatic degradation of macro hydrogels.

Thermo-responsive shell cross-linked PMMA-b-P(NIPAAm-co-NAS) micelles for drug delivery.

Thermo-responsive amphiphilic poly(methyl methacrylate)-b-poly(N-isopropylacrylamide-co-N-acryloxysuccinimide) (PMMA-b-P(NIPAAm-co-NAS)) block copolymer was synthesized by successive RAFT polymerizations. The uncross-linked micelles were facilely prepared by directly dissolving the block copolymer in an aqueous medium, and the shell cross-linked (SCL) micelles were further fabricated by the addition of ethylenediamine as a di-functional cross-linker into the micellar solution. Optical absorption measurements showed that the LCST of uncross-linked and cross-linked micelles was 31.0°C and 40.8°C, respectively. Transmission electron microscopy (TEM) showed that both uncross-linked and cross-linked micelles exhibited well-defined spherical shape in aqueous phase at room temperature, while the SCL micelles were able to retain the spherical shape with relatively smaller dimension even at 40°C due to the cross-linked structure. In vitro drug release study demonstrated a slower and more sustained drug release behavior from the SCL micelles at high temperature as compared with the release profile of uncross-linked micelles, indicating the great potential of SCL micelles developed herein as novel smart carriers for controlled drug release.

Galactosyl conjugated N-succinyl-chitosan-graft-polyethylenimine for targeting gene transfer.

Through incorporating lactobionic acid (LA) bearing a galactose group to N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI), NSC-g-PEI-LA copolymers were synthesized as gene vectors with hepatocyte targeting properties. The molecular weight and composition of NSC-g-PEI-LA copolymers were characterized using gel permeation chromatography (GPC) and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) respectively. Agarose gel electrophoresis assays showed good DNA binding ability of NSC-g-PEI-LA, and the particle size of the NSC-g-PEI-LA/DNA complexes were between 150 and 400 nm as determined by a Zeta sizer. The NSC-g-PEI-LA/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The zeta potentials of these complexes were increased with the weight ratio of NSC-g-PEI-LA/DNA. NSC-g-PEI-LA has a lower cytotoxicity than PEI (25 kDa) and the toxicity decreased with increasing substitution of LA. The transfection efficiency of different complexes was evaluated by luciferase assay. Compared with PEI (25 kDa) and NSC-g-PEI/DNA, NSC-g-PEI-LA showed good transfection activity and cell specificity to HepG2 cells. The results suggested that NSC-g-PEI-LA has the potential to be used as a safe and effective targeting gene vector.

Chitosan based oligoamine polymers: synthesis, characterization, and gene delivery.

A series of chitosan-based oligoamine polymers was synthesized from N-maleated chitosan (NMC) via Michael addition with diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and linear polyethylenimine (M(n) 423), respectively. The resulted polymers exhibited well binding ability to condense plasmid DNA to form complexes with size ranging from 200 to 600 nm when the polymer/DNA weight ratio was above 7. The polymer/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The cytotoxicity assay showed that the synthesized polymers were less toxic than that of PEI(25 K). The gene transfection effect of resulted polymers was evaluated in 293T and HeLa cells, and the results showed that the gene transfection efficiency of these polymers was better than that of chitosan. Moreover, the transfection efficiency was dependent on the length of the oligoamine side chains and the molecular weight of the chitosan derivatives.

Toward the development of partially biodegradable and injectable thermoresponsive hydrogels for potential biomedical applications.

A series of hydrogels containing a biodegradable dextran (Dex) chain grafted with a hydrophobic poly(-caprolactone)-2-hydroxylethyl methacrylate (PCL-HEMA) chain and a thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) chain were synthesized. The molecular weight of PCL-HEMA was determined by gel permeation chromatography, and the inner morphology of the hydrogel was observed by scanning electron microscopy. The release profiles from the hydrogels were investigated using bovine serum albumen as a model drug. It was found that the release behavior could be adjusted by varying the composition of the hydrogel. In vitro cytotoxicity studies of the hydrogels showed that the copolymer Dex-PCL-HEMA/PNIPAAm exhibited low cytotoxicity. The in vivo degradation and histological studies demonstrated that the hydrogels had good biocompatibility and were promising for use as an injectable polymeric scaffold for tissue engineering applications.

Bone marrow stem cells implantation with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel improves cardiac function after myocardial infarction.

Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable alpha-cyclodextrin/poly(ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly(ethylene glycol) (MPEG-PCL-MPEG) hydrogel could improve cell transplant retention and survival, reduce infarct expansion and inhibit left ventricle (LV) remodeling. Bone marrow-derived stem cells (BMSCs) were encapsulated in alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel and maintained their morphologies during the cell culturing. MTT assays were used for in vitro cell viability studies of the hydrogel and were shown to be non-cytotoxic. Seven days after MI, 100 microl of alpha-cyclodextrin solution containing 2 x 10(7) BMSCs and 100mul of MPEG-PCL-MPEG solution were injected into the infarcted myocardium simultaneously and the solutions solidified immediately. Injection of culture medium or cell alone served as controls. Four weeks after treatment, histological analysis indicated that the hydrogel was absorbed, and the injection of BMSCs with hydrogel had increased cell retention and vessel density around the infarct, and subsequently prevented scar expansion compared with BMSCs injection alone. Echocardiography studies showed that injection of BMSCs with hydrogel increased the LV ejection function and attenuated left ventricular dilatation. This study indicated that the injection of BMSCs with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel was an effective strategy which could enhance the effect of cellular transplantation therapy for myocardial infarction.

Peptide-functionalized thermo-sensitive hydrogels for sustained drug delivery.

In this study, a KRGDKK (Lys-Arg-Gly-Asp-Lys-Lys) peptide with a RGD sequence is utilized as a functional group to synthesize a novel thermo-sensitive hydrogel. The KRGDKK peptide prepared by a solid phase synthesis approach is coupled to the ends of a poly[(epsilon-caprolactone)-co-lactide]-poly(ethylene glycol)-poly[(epsilon-caprolactone)-co-lactide] (PCLA-PEG-PCLA) triblock copolymer to obtain peptide-PCLA-PEG-PCLA-peptide. The self-assembly behavior of both PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide copolymers in aqueous solution is investigated, and hydrogels prepared from PCLA-PEG-PCLA and peptide-PCLA-PEG-PCLA-peptide are also prepared. An in vitro cell viability study demonstrated that the peptide-PCLA-PEG-PCLA-peptide hydrogels do not exhibit an apparent cytotoxicity, which suggests that the hydrogels have promising potential as injectable drug-delivery systems. Furthermore, compared with the PCLA-PEG-PCLA hydrogels, the peptide-PCLA-PEG-PCLA-peptide hydrogels display improved mechanical properties because of hydrogen bonding between the amino groups of KRGDKK. An in vitro drug release study showed that the peptide-PCLA-PEG-PCLA-peptide hydrogels exhibit outstanding controlled release properties and the release of the drug could be sustained for more than a month without initial burst.

Galactosylated fluorescent labeled micelles as a liver targeting drug carrier.

Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g-dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can self-assemble into stable micelles in aqueous medium and in serum. Transmission electron microscopy (TEM) images showed that the self-assembled micelles were regularly spherical in shape. Micelle size determined by size analysis was around 120 nm. The anti-inflammation drug prednisone acetate as a model drug was loaded in the polymeric micelles, and the in vitro drug release was investigated. The galactosylated micelles could be selectively recognized by HepG2 cells and subsequently accumulate in HepG2 cells. The in vivo study demonstrated the relative uptake of the micelles by liver is much higher than the other tissues, indicating that the galactosylated micelles have great potential as a liver targeting drug carrier.

Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction.

Myocardial infarction (MI) and the subsequent heart failure remain one of the leading causes of morbidity and mortality world wide. A number of studies have demonstrated that bioderived materials improve cardiac function after implantation because of their angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricular (LV) function through its prevention of paradoxical systolic bulging. To test this hypothesis, infarction was induced in rabbit myocardium by coronary artery ligation. After 1 week, 200-microL alpha-cyclodextrin (alpha-CD)/MPEG-PCL-MPEG hydrogel was injected into the infarcted myocardium. Injection of phosphate buffered saline (PBS) served as controls. Twenty-eight days after the treatment, histological analysis indicated that the injection of hydrogel prevented scar expansion and wall thinning compared with the control (p < 0.05) without more microvessel density in infarcted myocardium (p = 0.70). LV ejection fraction, determined by echocardiography, was significantly greater in the hydrogel-treated group (56.09% +/- 8.42%) than the control group (37.26% +/- 6.36%, p = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 +/- 0.33 cm and 1.74 +/- 0.30 cm, respectively, in the control group. Smaller LV end-diastolic diameter (1.61 +/- 0.26 cm, p = 0.005) and smaller end-systolic diameter (1.17 +/- 0.23 cm, p = 0.001) were found in the hydrogel-treated group. These results suggest that alpha-CD/MPEG-PCL-MPEG hydrogel could serve as an injectable biomaterial that prevents LV remodeling and dilation for the treatment of MI.