Macromolecular bioscience最新文献

Front Cover: The cover art illustrates a multifunctional HAP-CNT-Ce hybrid coating designed for orthopaedic implants. The synergy of Ce ions and CNTs enhances mechanical strength, antioxidant activity, and osteogenic potential, promoting advanced bone regeneration and implant integration. More details can be found in the Research Article by Amrita Biswas, Kantesh Balani, Shikha Awasthi, and co-workers (DOI: 10.1002/mabi.202500384).

Bone repair remains a significant challenge in orthopedics and reconstructive surgery, especially in complex fractures and large tissue defects. Biomaterials such as graphene oxide (GO) and poly-L-lactic acid (PLLA) are promising due to their physicochemical properties and biocompatibility. However, the immune response plays a critical role in graft success. In this study, PLLA/GO scaffolds are implanted in the right antimeres of nine goat mandibles, while the left antimeres are stabilized with titanium plates and serve as controls. Samples are collected at 15-, 45-, and 60-days post- implantation and examined using histology and immunohistochemistry to assess inflammation, bone organization, and bone-implant integration. At 15 days, hematoxylin and eosin staining show early inflammatory reactions at the PLLA/GO interface, whereas control samples display regular histological patterns. At 45 days, denser and more compact bone tissue indicate progressive structural organization. By 60 days, the samples present advanced bone maturation and active osteogenesis. Steven's Blue staining confirms mineral deposition, and osteoblast-like cells deposit new matrix at the scaffold-tissue interface. Immunohistochemical detection of osteocalcin and VEGF reveals osteoblastic activity and angiogenesis. These results demonstrate that PLLA/GO scaffolds promote bone regeneration and integration, supporting their potential for clinical application in mandibular repair.

Urinary catheterization is a common procedure, affecting 15%-25% of hospitalized patients. This procedure, however, often results in bacterial infections, primarily caused by biofilm-forming Gram-negative bacteria that adhere to the catheter surface. To address this challenge, we developed a polymer-based antimicrobial coating using polydopamine (PD) embedded with gentamicin (Gent). We evaluated the antibiofilm efficacy of this coating (PD-Gent) using a biofilm-forming isolate of Pseudomonas aeruginosa (PAO1) as P. aeruginosa is commonly implicated in catheter-related infections. We observed that the PD-Gent coating significantly reduced biofilm formed by PAO1 compared to the uncoated control. Importantly, the coating maintained its antibiofilm activity across diverse substrates, including polystyrene, poly(vinyl chloride), and silicone. The approach was further extended to incorporate other antibiotics (tobramycin, amikacin), demonstrating adaptability to multiple antimicrobial agents. Finally, artificial urine inoculated with PAO1 was deployed through PD-Gent-coated silicone Foley catheters under continuous flow for 24 h. Despite this continuous introduction of PAO1, the coated catheters inhibited biofilm formation by three-fold compared to the uncoated control catheters. These findings underscore the promise of PD-Gent as a robust, versatile coating with strong potential to significantly reduce the incidence of catheter-associated infections in clinical settings.

Glaucoma, a major global health issue, is the second leading cause of blindness. Topical eye drops are commonly used due to their simplicity, but the eye's protective barriers hinder optimal drug concentration at the target site. This study addresses these challenges by developing a novel dual-drug delivery system, integrating polycaprolactone microparticles loaded with latanoprost(hydrophobic) and timolol maleate(hydrophilic) antiglaucoma drugs into a gelatin-alginate hydrogel matrix. There is a fundamental challenge to combine both drugs in the same delivery system with a controlled release profile. Hydrogel-microparticles(HMPs) were assessed via in vitro drug-release and cell culture for biocompatibility with Raman analysis for chemical compatibility and drug diffusivity. Results showed that the hydrogel-microparticle system has prolonged drug release for up to 32 days. Raman analysis confirmed the chemical compatibility of the formulation components, and in vitro biocompatibility studies demonstrate that the HMPs system is biocompatible and exhibits minimal toxicity to the cells. This novel HMPs system can serve as a flexible, controlled release platform modulating the release profile. Our study highlights that the polymer and drug properties, along with the external matrix, were key factors influencing the drug release behavior of the formulations, and the proposed HMPs system can potentially be considered for glaucoma therapy.

Using Response Surface Methodology (RSM) to optimise cultivation conditions showed that Trichoderma koningiopsis EPS biosynthesis depended on an alkaline pH (>9.0) and a high nitrogen concentration (≥20 g/L). This resulted in a yield increase of over 60% compared to the control conditions. Three wall polymer fractions were extracted from the obtained biomass: cold water soluble (WPSZ), hot water soluble (WPSC), and alkali soluble (WPSNaOH). These accounted for 13.3, 1.8, and 20.2% of the dry weight of the mycelium, respectively. Structural analyses revealed that the obtained EPS was mannan, with the WPS fractions consisting predominantly of (1→4)-Glc residues branching at the (1→3,6) and (1→4,6) positions. FT-IR and FT-Raman analyses revealed that α-bonds predominated in the WPSZ and WPSC fractions, whereas β-bonds predominated in the EPS and WPSNaOH fractions. This was confirmed by NMR analysis. The obtained polymer fractions (PS) exhibited antioxidant properties using the ABTS, DPPH, and FRAP methods, as well as the ability to bind bisphenol A from an aqueous environment. The most significant property of PS polymers is their ability to reduce germination and inhibit mycelial growth of the phytopathogenic Fusarium culmorum strain. These polymers exhibit various bioactive properties and have potential applications in many areas of human life.

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter that possesses multiple pathological and physiological functions, including anti-inflammation, anti-thrombosis, anti-calcification, inhibition of intimal hyperplasia, and promotion of angiogenesis. Therefore, we aim to design an H₂S-releasing resorbable synthetic graft that utilizes the therapeutic benefits of the H₂S to modulate the graft regeneration. To ease fabrication of the H₂S-releasing graft, we have designed a pair of functional polyesters that are electrospinnable and photocurable to form an elastic fibrous conduit. The conduit bears free thiol groups that are conjugated with a methacrylated H₂S donor through thiol-ene click chemistry to form an H₂S-releasing graft. The graft can sustainably release H₂S over ∼12 days in vitro. Differing from prior designs, the H₂S-releasing graft simultaneously possesses key features of a robust elasticity, and suitable mechanical properties, degradation rate and porosity. At the proof-of-concept stage, we examined the H₂S stimulation on endothelial cell growth using the graft with a low H₂S releasing rate. The results demonstrated that the graft with sustained H₂S release could significantly promote endothelial cell growth in vitro. This work paved the way for in vivo evaluation of the H₂S-releasing graft.

Conventional gelatin's gel-to-sol transition upon heating restricts its utility in biomedical applications that benefit from a gel state at physiological temperatures such as Pluronic F127 and poly(NIPAAm). Herein, we present "rev-Gelatin", a gelatin engineered with reverse thermo-responsive properties that undergoes a sol-to-gel transition as temperature rises from ambient to body temperature. Inspired by the phase dynamics of common materials like candy and ice cubes, whose surfaces soften or partially melt under warming, facilitating inter-object adhesion- rev-Gelatin leverages this concept to achieve fluidity at room temperature for easy injectability. At ambient temperature, rev-Gelatin exists as a microgel solution with sufficient fluidity in the sol state. However, upon exposure to elevated temperatures approaching physiological temperature, rev-Gelatin microgels coalesce through surface melting, forming a stable gel. This sol-to-gel transition is especially advantageous for hemostatic applications. Upon contact with blood, the temperature elevation induces rapid gelation of rev-Gelatin, effectively creating a barrier that reduces bleeding time and blood loss. Additionally, rev-Gelatin shows promise as a submucosal injection agent for gastrointestinal surgeries, making it a new class of thermo-sensitive biomaterials.

Poly[(R)-3-hydroxybutyrare-co-(R)-3-hydroxypivalate] (P(3HB-co-3HPi)) films, a type of polyhydroxyalkanoate (PHA), are oxidized using photoactivated chlorine dioxide radical (ClO₂•) gas to generate carboxyl groups and loaded with divalent metal cations, including Cu²⁺, Zn²⁺, and Ca²⁺ ions, via ionic interactions. The P(3HB-co-3HPi) films loaded with Cu²⁺ ions exhibit enhanced antibacterial activity against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) compared with untreated P(3HB-co-3HPi) films. In seawater, the biodegradation of these Cu²⁺ and Zn²⁺-loaded films is initially inhibited by the antimicrobial activity of the cations and occurs gradually; therefore, loading antimicrobial divalent metal cations onto the surface of PHAs inhibits biodegradation in seawater temporarily but allows biodegradation to occur with time. These results indicate that PHAs could be employed in seawater without undergoing biodegradation, such that PHAs could be used in fishing gear, including fishing lines that are repeatedly exposed to seawater for short periods.

This study investigates a multifunctional hydrogel system integrating carboxymethyl cellulose (CMC) in a 3D-printed limonene (LIM) scaffold coated with poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS). The system allows to enhance wound healing, prevent infections, and monitor the healing progress. CMC is crosslinked with citric acid (CA) to form the hydrogel matrix (CMC-CA), while the 3D-printed limonene (LIM) scaffold is embedded within the hydrogel to provide mechanical support. PEDOT:PSS and curcumin-loaded PEDOT (PEDOT:CUR) nanoparticles are integrated into the hydrogel-membrane system for electrochemical detection of bacterial infection and controlled delivery of the antibacterial drug. The CMC-CA hydrogel exhibits excellent mechanical properties, suitable for conforming to irregular wound surfaces. In addition to provide additional mechanical support, the LIM scaffold is used as a pillar for the incorporation of PEDOT The integration of PEDOT:PSS and PEDOT:CUR enable not only real-time monitoring of bacterial growth but also the electrostimulated release of curcumin, which demonstrates antibacterial activity against Escherichia coli and Staphylococcus aureus. Electrostimulation of the CMC-CA/LIM/PEDOT system promotes cell proliferation, supporting accelerated wound healing. In conclusion, the CMC-CA/LIM/PEDOT system combines mechanical support, infection monitoring, and enhanced healing through controlled drug delivery and electrical stimulation, addressing critical challenges in wound management.

Wound healing is an intricate process that involves various biochemical pathways at each stage of tissue regeneration. Wound therapy is a series of distinct treatment stages that has a limited efficacy if wounds are of complex etiologies. A modern approach to this problem may be the development of bifunctional adaptive biohybrid systems that can concurrently affect pathogens' growth, inflammation, and tissue regeneration. We have developed biohybrid living material with antibacterial and regenerating properties based on induced hormesis by oxidative stress onto probiotic bacteria with prolonged synthesis of hydrogen peroxide, increased antibacterial action, and regeneration of the burn wound. Material demonstrates almost complete wound healing with a wound area difference 3-4 times with natural healing in vivo burn wound model for 21 days, antibacterial activity against wound antibiotic-resistance pathogens Escherichia coli K12 and Staphylococcus aureus ATCC 29213 in 4 and 5-fold, respectively in co-cultivation model, and has no toxicity to human skin fibroblasts and β-hemolysis in the in vitro model. Our findings promise the improving tissue regeneration of burn wounds, therapy against antibiotic-resistance pathogens by eliminating antibiotics, and other classical bactericides.