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Biomaterials Science Jun 2024The treatment of various types of wounds such as dermal wounds, multidrug resistant bacteria-infected wounds, and chronic diabetic wounds is one of the critical... (Review)
Review
The treatment of various types of wounds such as dermal wounds, multidrug resistant bacteria-infected wounds, and chronic diabetic wounds is one of the critical challenges facing healthcare systems. Delayed wound healing can impose a remarkable burden on patients and health care professionals. In this case, given their unique three-dimensional porous structure, biocompatibility, high hydrophilicity, capability to provide a moist environment while absorbing wound exudate, permeability to both gas and oxygen, and tunable mechanical properties, hydrogels with antibacterial function are one of the most promising candidates for wound healing applications. Polylysine is a cationic polymer with the advantages of inherent antibacterial properties, biodegradability, and biocompatibility. Therefore, its utilization to engineer antibacterial hydrogels for accelerating wound healing is of great interest. In this review, we initially discuss polylysine properties, and then focus on the most recent advances in polylysine-containing hydrogels (since 2016) prepared using various chemical and physical crosslinking methods for hemostasis and wound healing applications. Finally, the challenges and future directions in the engineering of these antibacterial hydrogels for wound healing are discussed.
Topics: Hydrogels; Wound Healing; Polylysine; Anti-Bacterial Agents; Humans; Animals; Hemostatics; Hemostasis
PubMed: 38747970
DOI: 10.1039/d3bm01792c -
Biomaterials Science Sep 2023Development of novel therapeutic agents that possess different anticancer mechanisms from the traditional antitumor drugs is highly attractive as no medication can cure...
Development of novel therapeutic agents that possess different anticancer mechanisms from the traditional antitumor drugs is highly attractive as no medication can cure all types of cancers. Herein, we report a rational design of antitumor lipo-polylysine polymers as synthetic mimics of biosynthetic lipopeptide surfactants featuring antimicrobial or cytotoxic activities for cancer therapy. The optimal polymer shows a wide range of anticancer activities against multiple cancer cells, including highly metastatic and drug-resistant ones, but low toxicity to normal cells. Mechanism studies show that the optimal polymer can interact with the membrane of cancer cells and induce cell necrosis by triggering cell membrane perforation, which is different from the therapeutic mechanisms of traditional anticancer drugs. studies imply that the optimal polymer efficiently inhibits tumor growth without causing obvious side effects on a C26 graft tumor model. Overall, the lipopeptide-mimicking lipo-polylysine with the advantages of easy synthesis and low cost provides a new anticancer strategy with high efficacy and biocompatibility.
Topics: Humans; Polylysine; Antineoplastic Agents; Neoplasms; Lipopeptides; Polymers
PubMed: 37605903
DOI: 10.1039/d3bm01099f -
International Journal of Biological... Dec 2023With increasing awareness on environmental protection and food safety, the development of biodegradable antimicrobial packaging materials has been paid growing emphasis....
With increasing awareness on environmental protection and food safety, the development of biodegradable antimicrobial packaging materials has been paid growing emphasis. In this work, starch/poly(butylene adipate-co-terephthalate)/ε-polylysine hydrochloride films were prepared by extrusion blowing, and five commercial organically modified nanomontmorillonites (OMMT, including DK1, DK2, DK3, DK4, and DK5) were used as reinforcing agents. Intercalated structures were formed in the nanocomposite films, especially for those with DK3 and DK4 owing to their higher hydrophobicity and larger interlayer spacing. Adding OMMT weakened hydrogen bonds and the gelatinization/plasticization degree of starch. Morphology analysis revealed that the agglomeration of OMMT occurred in the films, but the film containing DK3 still showed a relatively homogeneous microstructure. Loading OMMT enhanced the strength, deformation resistance, thermal stability, surface hydrophobicity, but decreased barrier properties and water sensitivity of the films. Antimicrobial activity showed that the OMMT and ε-polylysine hydrochloride possessed a synergistic effect against Staphylococcus aureus and Escherichia coli. The maximum inhibition rate was observed in that with DK4, approaching 100 %. Findings supported the application of commercial OMMT in manufacturing biodegradable antimicrobial blown films.
Topics: Polyesters; Polylysine; Starch; Anti-Infective Agents; Adipates
PubMed: 37652334
DOI: 10.1016/j.ijbiomac.2023.126609 -
Carbohydrate Polymers Aug 2023In recent years, the incidence of diabetic skin ulcers has increased. Because of its extremely high disability and fatality rate, it brings a huge burden to patients and...
In recent years, the incidence of diabetic skin ulcers has increased. Because of its extremely high disability and fatality rate, it brings a huge burden to patients and society. Platelet-rich plasma (PRP) contains a large number of biologically active substances and is of great clinical value in the treatment of various wounds. However, its weak mechanical properties and the consequent abrupt release of active substances greatly limit its clinical application and therapeutic efficacy. Here, we chose hyaluronic acid (HA) and ε-polylysine (ε-PLL) to prepare a hydrogel with the ability to prevent wound infection and promote tissue regeneration. At the same time, using the macropore barrier effect of the lyophilized hydrogel scaffold, platelets in PRP are activated with calcium gluconate in the macropores of the scaffold carrier, and fibrinogen from PRP is converted in a fibrin-packed network forming a gel that interpenetrates the hydrogel scaffold carrier, thus creating a double network hydrogel with slow-release of growth factors from degranulated platelets. The hydrogel not only showed better performance in functional assays in vitro, but also showed more superior therapeutic effects in reducing inflammatory response, promoting collagen deposition, facilitating re-epithelialization and angiogenesis in the treatment of full skin defects in diabetic rats.
Topics: Rats; Animals; Hydrogels; Hyaluronic Acid; Delayed-Action Preparations; Diabetes Mellitus, Experimental; Platelet-Rich Plasma; Bandages
PubMed: 37173024
DOI: 10.1016/j.carbpol.2023.120924 -
International Journal of Biological... Nov 2023The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity,...
The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs.
Topics: Alginates; Polylysine; Nanoparticles; Particle Size; Anti-Infective Agents; Staphylococcus aureus; Molecular Weight; Escherichia coli; Anti-Bacterial Agents; Microbial Sensitivity Tests; Drug Carriers
PubMed: 37595718
DOI: 10.1016/j.ijbiomac.2023.126329 -
Journal of Controlled Release :... Nov 2023Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a...
Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a lack of a precise, multitemporal, integrated drug delivery system for medications administered in both phases. In this study, we prepare a hybrid polylysine-based hydrogel (PBH@AGN) comprising short-term release of pH-responsive aminoguanidine nanoparticles (AGN) and sustained release of extracellular vesicles (EVs) for synergistic SCI treatment. When AGN is exposed to the acidic environment at the injury site, it quickly diffuses out of the hydrogel and releases the majority of the aminoguanidine within 24 h, reducing oxidative stress in lesion tissues. Enriched EVs are gradually released from the hydrogel and remain in the tissue for weeks, providing a long-term anti-inflammatory effect and further ensuring axonal regeneration. Fast-releasing aminoguanidine can cooperate with slow-release EVs to treat SCI more effectively by reducing the production of proinflammatory cytokines and blocking the TLR4/Myd88/NF-κB inflammatory pathway, creating a sustained anti-inflammatory microenvironment for SCI recovery. Our in vivo experiments demonstrate that PBH@AGN reduces the occurrence of scar tissue, encourages remyelination, and speeds up axonal regeneration. Herein, this multi-drug delivery system, which combines the acute release of aminoguanidine and the sustained release of EVs is highly effective for synergistically managing the challenging pathological processes after SCI.
Topics: Humans; Hydrogels; Polylysine; Delayed-Action Preparations; Spinal Cord Injuries; Anti-Inflammatory Agents; Extracellular Vesicles; Nanoparticles; Spinal Cord
PubMed: 37722419
DOI: 10.1016/j.jconrel.2023.09.026 -
Journal of the Mechanical Behavior of... Sep 2023Clinical adhesives for suture-less wound closure remain the problem of poor biocompatibility, weak adhesive strength, and no endogenous antibacterial ability. Here, we...
Clinical adhesives for suture-less wound closure remain the problem of poor biocompatibility, weak adhesive strength, and no endogenous antibacterial ability. Here, we designed a novel antibacterial hydrogel (CP-Lap hydrogel) consisting of chitosan and ε-polylysine after being modified with gallic acid (pyrogallol structure). The hydrogel was crosslinked by glutaraldehyde and Laponite via Schiff base and dynamic Laponite-pyrogallol interaction, free from heavy metal and oxidants. Given its dual crosslinking feature, the CP-Lap hydrogel exhibited adequate mechanical strength (150-240 kPa) and demonstrated swelling and degradation resistance. For a typical lap shear test with pigskin, the apparent adhesion strength of the CP-Lap hydrogel could be enhanced to ∼30 kPa benefiting from the O blocking effect provided by nanoconfinement space between Laponite. In addition, the hydrogel showed effective antibacterial properties and excellent biocompatibility. The results indicated that this hydrogel has great potential for wound-closing bioadhesives to avoid chronic infections and further harm.
Topics: Hydrogels; Tissue Adhesives; Pyrogallol; Adhesives; Anti-Bacterial Agents
PubMed: 37423008
DOI: 10.1016/j.jmbbm.2023.106009 -
International Journal of Molecular... Jul 2023The outer membrane of Gram-negative bacteria contains a variety of pore-forming structures collectively referred to as porins. Some of these are voltage dependent, but...
The outer membrane of Gram-negative bacteria contains a variety of pore-forming structures collectively referred to as porins. Some of these are voltage dependent, but weakly so, closing at high voltages. Triplin, a novel bacterial pore-former, is a three-pore structure, highly voltage dependent, with a complex gating process. The three pores close sequentially: pore 1 at positive potentials, 2 at negative and 3 at positive. A positive domain containing 14 positive charges (the voltage sensor) translocates through the membrane during the closing process, and the translocation is proposed to take place by the domain entering the pore and thus blocking it, resulting in the closed conformation. This mechanism of pore closure is supported by kinetic measurements that show that in the closing process the voltage sensor travels through most of the transmembrane voltage before reaching the energy barrier. Voltage-dependent blockage of the pores by polyarginine, but not by a 500-fold higher concentrations of polylysine, is consistent with the model of pore closure, with the sensor consisting mainly of arginine residues, and with the presence, in each pore, of a complementary surface that serves as a binding site for the sensor.
Topics: Humans; Ion Channel Gating; Porins; Thiourea; Translocation, Genetic
PubMed: 37511231
DOI: 10.3390/ijms241411473 -
Food Research International (Ottawa,... Jul 2024In light of the commendable advantages inherent in natural polymers such as biocompatibility, biodegradability, and cost-effectiveness, researchers are actively engaged... (Review)
Review
In light of the commendable advantages inherent in natural polymers such as biocompatibility, biodegradability, and cost-effectiveness, researchers are actively engaged in the development of biopolymer-based biodegradable food packaging films (BFPF). However, a notable limitation is that most biopolymers lack intrinsic antimicrobial activity, thereby restricting their efficacy in food preservation. To address this challenge, various active substances with antibacterial properties have been explored as additives to BFPF. Among these, ε-polylysine has garnered significant attention in BFPF applications owing to its outstanding antibacterial properties. This study provides a brief overview of the synthesis method and chemical properties of ε-polylysine, and comprehensively examines its impact as an additive on the properties of BFPF derived from diverse biopolymers, including polysaccharides, proteins, aliphatic polyesters, etc. Furthermore, the practical applications of various BFPF functionalized with ε-polylysine in different food preservation scenarios are summarized. The findings underscore that ε-polylysine, functioning as an antibacterial agent, not only directly enhances the antimicrobial activity of BFPF but also serves as a cross-linking agent, interacting with biopolymer molecules to influence the physical and mechanical properties of BFPF, thereby enhancing their efficacy in food preservation.
Topics: Polylysine; Food Packaging; Biopolymers; Food Preservation; Anti-Bacterial Agents; Edible Films
PubMed: 38763652
DOI: 10.1016/j.foodres.2024.114390 -
Journal of Functional Biomaterials Dec 2023With the phase-out of amalgam and the increase in minimally invasive dentistry, there is a growing need for high-strength composite materials that can kill residual...
With the phase-out of amalgam and the increase in minimally invasive dentistry, there is a growing need for high-strength composite materials that can kill residual bacteria and promote tooth remineralization. This study quantifies how antibacterial polylysine (PLS) and re-mineralizing monocalcium phosphate monohydrate (MCPM) affect biofilms and the strength of dental composites. For antibacterial studies, the MCPM-PLS filler percentages were 0-0, 8-4, 12-6, and 16-8 wt% of the composite filler phase. Composite discs were immersed in 0.1% sucrose-supplemented broth containing (UA159) and incubated in an anaerobic chamber for 48 h. Surface biomass was determined by crystal violet (CV) staining. Growth medium pH was measured at 24 and 48 h. Biofilm bacterial viability (CFU), exo-polysaccharide (water-soluble glucan (WSG) and water-insoluble glucan (WIG)), and extracellular DNA (eDNA) were quantified. This was by serial dilution plate counting, phenol-sulfuric acid microassay, and fluorometry, respectively. The biaxial flexural strengths were determined after water immersion for 1 week, 1 month, and 1 year. The MCPM-PLS wt% were 8-4, 8-8, 16-4 and 16-8. The normalized biomass, WSG, and WIG showed a linear decline of 66%, 64%, and 55%, respectively, as the PLS level increased up to 8%. The surrounding media pH (4.6) was all similar. A decrease in bacterial numbers with the 12-6 formula and a significant reduction with 16-8 compared to the 0-0 formulation was observed. The eDNA concentrations in biofilms formed on 12-6 and 16-8 formulations were significantly less than the 0-0 control and 8-4 formulations. Doubling MCPM and PLS caused a 14 and 19% reduction in strength in 1 week, respectively. Average results were lower at 1 month and 1 year but affected less upon doubling MCPM and PLS levels. Moreover, a 4% PLS may help to reduce total biomass and glucan levels in biofilms on the above composites. Higher levels are required to reduce eDNA and provide bactericidal action, but these can decrease early strength.
PubMed: 38248680
DOI: 10.3390/jfb15010013