Bioactive Polymer Research Articles

Electroactive functional microenvironments from bioactive polymers: A new strategy to address cancer.

The present work reports on a new approach based on electroactive microenvironments to mitigate skeletal muscle cancer. For that, piezoelectric films based on poly(vinylidene fluoride) have been applied to evaluate the influence of mechano- and/or electrical stimuli on rhabdomyosarcoma (RMS) proliferation. Human embryonal rhabdomyosarcoma (RD) cells were cultured on PVDF pristine films with different surface charge (non-poled, poled+ and poled-) and magnetic composites (10% and 20% Fe3O4, and 20% CFO filler content) to allow magneto-mechanical and magnetoelectrical stimulation films. Electrospun PVDF pristine (oriented and randomly) and magnetic (10% Fe3O4) fiber mats were also evaluated to take into consideration the morphology effect on cell response. It was found that the mechanical stimuli enhance RMS proliferation whereas the mechano-electrical decreases it. It was also verified that the RD cells proliferate better on randomly oriented fibers, whereas myoblast cells do it better in oriented ones. The obtained results confirm that electroactive microenvironments can be used to develop novel and effective approaches to deal with RMS cancer, that can be extrapolated to others cancer types.

Polydopamine Biomaterials for Skin Regeneration.

Designing biomaterials capable of biomimicking wound healing and skin regeneration has been receiving increasing attention recently. Some biopolymers behave similarly to the extracellular matrix (ECM), supporting biointerfacial adhesion and intrinsic cellular interactions. Polydopamine (PDA) is a natural bioadhesive and bioactive polymer that endows high chemical versatility, making it an exciting candidate for a wide range of biomedical applications. Moreover, biomaterials based on PDA and its derivatives have near-infrared (NIR) absorption, excellent biocompatibility, intrinsic antioxidative activity, antibacterial activity, and cell affinity. PDA can regulate cell behavior by controlling signal transduction pathways. It governs the focal adhesion behavior of cells at the biomaterials interface. These features make melanin-like PDA a fascinating biomaterial for wound healing and skin regeneration. This paper overviews PDA-based biomaterials' synthesis, properties, and interactions with biological entities. Furthermore, the utilization of PDA nano- and microstructures as a constituent of wound-dressing formulations is highlighted.

Production and Characterization of Exopolysaccharide From Newly Isolated Marine Probiotic Lactiplantibacillus plantarum EI6 With in vitro Wound Healing Activity.

Because of its safety, biological activities, and unique properties, exopolysaccharide (EPS) from lactic acid bacteria (LAB) has been developed as a potential biopolymer. A few studies have investigated the EPS produced by marine LAB. This study reports the wound healing activity of an EPS produced by a marine isolate identified as Lactiplantibacillus plantarum EI6, in addition to assessing L. plantarum EI6's probiotic properties. EI6 demonstrated promising antimicrobial activity against different pathogenic bacteria, as well as the ability to withstand stomach pH 3, tolerate 0.3% bile salt concentration, and exhibit no signs of hemolysis. Furthermore, EI6 was able to produce 270 mg/L of EPS upon growth for 48 h at 37°C in an MRS medium enriched with 1.0% of sucrose. The chemical features of the novel EI6-EPS were investigated: the UV-vis estimated a high carbohydrate content of ~91.5%, and the FTIR emphasized its polysaccharide nature by the characteristic hydroxyl, amide I, II, & III, and glycosidic linkage regions. The GC-MS and NMR analyses revealed the existence of five monosaccharides, namely, rhamnose, galactose, mannose, glucose, and arabinose, existing mainly in the pyranose form and linked together by α- and β-glycosidic linkages. EI6-EPS was found to be safe (IC50 > 100 μg/ml) and induced human skin fibroblasts (HSF) proliferation and migration. These findings imply that EI6 can be used as a safe source of bioactive polymer in wound care.

(1→3)-α-D-glucooligosaccharides as Elicitors Influencing the Activity of Plant Resistance Pathways in Wheat Tissues

Laetiporus sulphureus (Bull.: Fr.) Murrill is an arboreal species of the large-fruited Basidiomycota fungus from the Polyporales, family Laetiporaceae. The cell wall of this fungus is the source of many bioactive polymer compounds, including (1→3)-α-D-glucans. (1→3)-α-D-glucans can be hydrolyzed to shorter compounds, (1→3)-α-D-glucooligosaccharides (GOS), with different degrees of polymerization (DP). The use of GOS obtained from L. sulphureus (1→3)-α-D-glucans, as an elicitor of plant resistance, may be important for biological protection used in sustainable agriculture. In the presented study, GOS influenced the activity of antioxidant enzymes (Catalase−CAT, Ascorbate Peroxidase−APX, Guaiacol Peroxidase−GPX, and Superoxide Dismutase−SOD), lignin and flavonoids producing phenylpropanoids pathways (Phenylalanine Ammonia-Lyase−PAL and Tyrosine Ammonia-Lyase−TAL), and pathogen-related proteins (with Glucanase−GLUC and Chitinase−CHIT activity) in wheat (Triticum aestivum L.) seedling tissues. Other than that, the application of GOS increased the fresh weight of wheat stems and roots by 1.5–2-times, compared to the water control. The GOS at a concentration of 0.05% most strongly increased the activity of APX and GPX, where a 2-fold (up to 6000 U) and a 3-fold (up to 180 U) increase in enzymatic activity in wheat stems was observed, compared to the control. Simultaneously, 0.1% GOS significantly increased the activity of PAL (80 U in stems and 50 U in roots) and TAL (60 U in stems and 50 U in roots), where a 4–5-fold increase in enzymatic activity was observed, both in comparison to the water control and commercial elicitors (chitosan−CHI and laminarin−LAM). No effect of GOS on GLUC activity was observed, but a 1.5–2-fold increase in CHIT activity in plant tissues was noted. The complexity of the influence of GOS on the level of marker enzymes indicates the potential of their application in agriculture. This work is the first report of the successful use of (1→3)-α-D-glucooligosaccharides as an elicitor inducing resistance in the cereal plant (wheat).

Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering.

Developing bioactive biomaterials with highly controlled functions is crucial to enhancing their applications in regenerative medicine. Citrate-based polymers are the few bioactive polymer biomaterials used in biomedicine because of their facile synthesis, controllable structure, biocompatibility, biomimetic viscoelastic mechanical behavior, and functional groups available for modification. In recent years, various multifunctional designs and biomedical applications, including cardiovascular, orthopedic, muscle tissue, skin tissue, nerve and spinal cord, bioimaging, and drug or gene delivery based on citrate-based polymers, have been extensively studied, and many of them have good clinical application potential. In this review, we summarize recent progress in the multifunctional design and biomedical applications of citrate-based polymers. We also discuss the further development of multifunctional citrate-based polymers with tailored properties to meet the requirements of various biomedical applications.

Melanin biopolymer synthesis using a new melanogenic strain of Flavobacterium kingsejongi and a recombinant strain of Escherichia coli expressing 4-hydroxyphenylpyruvate dioxygenase from F. kingsejongi

BackgroundMelanins are a heterologous group of biopolymeric pigments synthesized by diverse prokaryotes and eukaryotes and are widely utilized as bioactive materials and functional polymers in the biotechnology industry. Here, we report the high-level melanin production using a new melanogenic Flavobacterium kingsejongi strain and a recombinant Escherichia coli overexpressing F. kingsejongi 4-hydroxyphenylpyruvate dioxygenase (HPPD).ResultsMelanin synthesis of F. kingsejongi strain was confirmed via melanin synthesis inhibition test, melanin solubility test, genome analysis, and structural analysis of purified melanin from both wild-type F. kingsejongi and recombinant E. coli expressing F. kingsejongi HPPD. The activity of F. kingsejongi HPPD was demonstrated via in vitro assays with 6 × His-tagged and native forms of HPPD. The specific activity of F. kingsejongi HPPD was 1.2 ± 0.03 μmol homogentisate/min/mg-protein. Bioreactor fermentation of F. kingsejongi produced a large amount of melanin with a titer of 6.07 ± 0.32 g/L, a conversion yield of 60% (0.6 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.03 g/L·h, indicating its potential for industrial melanin production. Additionally, bioreactor fermentation of recombinant E. coli expressing F. kingsejongi HPPD produced melanin at a titer of 3.76 ± 0.30 g/L, a conversion yield of 38% (0.38 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.04 g/L·h.ConclusionsBoth strains showed sufficiently high fermentation capability to indicate their potential as platform strains for large-scale bacterial melanin production. Furthermore, F. kingsejongi strain could serve as a model to elucidate the regulation of melanin biosynthesis pathway and its networks with other cellular pathways, and to understand the cellular responses of melanin-producing bacteria to environmental changes, including nutrient starvation and other stresses.

Special focus issue on targeted drug delivery for inflammatory lung diseases.

Special focus issue on targeted drug delivery for inflammatory lung diseases.

Multi-material cellular structured orthopedic implants design: In vitro and bio-tribological performance

In this study, Selective Laser Melting (SLM) was used to produce mono-material Ti64Al4V- and NiTi-cubic cellular structures with an open-cell size and wall thickness of 500 μm and 100 μm, respectively. Bioactive beta-tricalcium phosphate (βTCP) and polymer poly-ether-ether ketone (PEEK) were used to fill the produced structures open-cells, thus creating multi-material components. These structures were characterized in vitro in terms of cell viability, adhesion, differentiation and mineralization. Also, bio-tribological experiments were performed against bovine plate to mimic the moment of implant insertion. Results revealed that metabolic activity and mineralization were improved on SLM mono-material groups, when compared to the control group. All cell metrics were improved with the addition of PEEK, conversely to βTCP where no significant differences were found. These results suggest that the proposed solutions can be used to improve implants performance.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

WHEY BASED BIOPOLYMERIC COATING AS AN ALTERNATIVE TO IMPROVE QUALITY OF FRESH FRUITS (MALPIGHIA EMARGINATA D.C.) FROM SOUTHERN BRAZIL

Refrigeration and coating of active biopolymers are two potential approaches to extending the shelf life of fresh fruits. Thus, the aim of this study was to test the influence of storage temperature (5 and 10 °C ± 1 °C) and whey concentration (edible coating), on functional, physical-chemical, and microbiological characteristics of acerola stored for 12 days. Edible coatings were produced using whey (30% and 60%) and glycerol. Samples were compared to a control (no coating), during storage at both temperatures. Storage at 10 °C improved the maintenance of the acerola color, while storage at 5 °C increased the stability of vitamin C and decreased microbial growth (p ≤0.05). The application of edible coating reduced the total color variation and degradation (a*) at both temperatures. The concentration of whey influenced significantly (p≤0.05) on the vitamin C content (A10-60), and on the mesophilic (A5-60 and A10-60) and psychrotrophic bacteria (A10-60) counts.

Characterization of plasmatic proteins adsorption on poly(styrene sodium sulfonate) functionalized silicone surfaces

Proteins adsorption occurs spontaneously on biomaterial upon insertion within the body. The resulting protein layer influences biomaterial biocompatibility through enhanced bio-integration or, on the contrary, adverse reactions. Furthermore, upon adsorption, proteins can undergo modifications of their structure and, ultimately, their physicochemical properties and activity. Hence, the understanding of protein adsorption on implanted materials appears essential, as exemplified by silicone breast prostheses that might lead to serious health issues.Surface modifications with a bioactive polymer, poly(styrene sodium sulfonate)-polyNaSS, on a hydrophobic silicone surface that composes breast implants, have been successfully performed under UV irradiation by a radical surface polymerization. This strategy enhances cell biocompatibility and antibacterial features. Although detailed insights related to the mechanism are still scarce, polyNaSS is supposed to promote changes in the conformation and/or orientation of adsorbed plasma proteins, reducing the odd for a biofilm to form.The present work addresses more in-depth structural investigations of the adsorbed state of two plasma proteins: Bovine Serum Albumin (BSA), as a model protein, and fibronectin (FN), for its role in cell adhesion. Using Atomic force microscopy (AFM), we report that polyNaSS showed no significant impact on the BSA structure conversely to the FN one. However, imaging findings with AFM clearly outlined a change in the structural organization of FN, going from a nano fibrillar assembly with an average length of 130 nm to a globular one when the surface was grafted. Thus, it is highlighted that polyNaSS interacts specifically with FN. In addition, cell spreading assay of L929 fibroblasts on FN-coated surfaces with optical microscopy indicated no significant impact of the change in FN structure upon fibroblasts adhesion, which displayed active elongated shapes. The present features are crucial for understanding the cell adhesion mechanism induced by surface modification.

Au nanoparticles adorned chitosan-modified magnetic nanocomposite: An investigation towards its antioxidant and anti-hepatocarcinoma activity in vitro

• Supporting of Au NPs on chitosan-encapsulated magnetic Fe 3 O 4 nanoparticles. • The average diameter of the NPs was approximately 15–25 nm. • The cell viability of malignant liver cell line reduced dose-dependently in the presence of Fe 3 O 4 @CS-GA/Au nanocomposite. • Without significant toxicity against normal cell line. Chitosan is a linear polysaccharide and non-toxic bioactive polymer with a wide variety of applications due to its functional properties such as ease of modification and biodegradability. In this study, a green protocol for synthesis of Au nanoparticles (NPs) supported on chitosan-encapsulated magnetic Fe 3 O 4 NP is described. The morphological and physicochemical features of the material were determined using several advanced techniques like Fourier Transformed Infrared Spectroscopy (FT-IR), Field Emission Scanning Electron Microscopy (FE SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Diffraction (XRD), Inductively Coupled Plasma (ICP), Vibrating sample Magnetometer (VSM) and elemental mapping. The average diameter of the NPs was approximately 15–25 nm. In addition, the Fe 3 O@CS-GA/Au nanocomposite was engaged in biological assays like study of anti-oxidant properties by DPPH mediated free radical scavenging test using BHT as a reference molecule. Thereafter, on having a significant IC 50 value in radical scavenging assay, we extended the bio-application of the desired nanocomposite in anticancer study of HepG2 liver cancer cell line in-vitro conditions following MTT assay. The cell viability of malignant liver cell line reduced dose-dependently in the presence of Fe 3 O 4 @CS-GA/Au nanocomposite. As a result, synthesized stable Fe 3 O@CS-GA/Au nanocomposite show more significant anticancer activity against HepG2 cells at 161.25 µg concentration of NPs without significant toxicity against normal cell line. The recent results suggest that Fe 3 O 4 @CS-GA/Au nanocomposite have a suitable anticancer activity against liver cell lines.

“Clay-corn-caprolactone” a novel bioactive clay polymer nanofibrous scaffold for bone tissue engineering

Osteoconductive bone tissue scaffolds are of particular interest. Clay composed of aluminosilicate can play an essential role in bone repair and regeneration, enhancing osteoblastic differentiation and apatite deposition. Current research focuses on the fabrication of illite incorporated polycaprolactone/zein electrospun scaffolds. The prepared scaffolds by varying concentrations of Illite were characterized physiochemically and biologically. The composite scaffolds were analyzed for surface morphology, mechanical properties, thermal characteristic, crystal structure, surface wettability, and chemical modification. Biocompatibility of the composite scaffold was checked against the MC3T3-e1 cell line as a model. The biomineral apatite deposition was determined by incubating the scaffolds in simulated body fluid. The alkaline phosphatase staining evaluated osteoblastic differentiation. The results show that the clay composite scaffolds showed reduced fiber diameters and enhanced wettability. The addition of Illite improved the tensile strength and the Youngs Modulus of the composite scaffolds. The in vitro biomineralization of the composite scaffolds improved calcium deposition with the maximum Ca/P ratio of 1.55. The WST-1 assay and ALP staining show that the composite scaffolds have better cell viability and osteoblastic differentiation than the PCL/zein scaffolds. The overall results show that the clay-corn-caprolactone scaffold is a promising material for bone tissue engineering.

Influence of poly(styrene sodium sulfonate) grafted silicone breast implant’s surface on the biological response and its mechanical properties

Prior to its commercialization, a biomaterial must fulfill the regulation in place. The International Organization for Standardization outlines the requirements needed for a material in order to guarantee safety and quality. In previous work, we have successfully grafted a bioactive polymer known as poly(styrene sodium sulfonate) – (polyNaSS) on silicone breast implants’ surfaces using UV irradiation. This paper intends to study the effect of the polyNaSS grafting parameters. It includes the study of (i) the effect of only UV irradiation and (ii) the presence of the polyNaSS grafted silicone on both the mechanical properties of the material and the biological response using the L929 fibroblast cell line for biocompatibility investigations. PolyNaSS aims to overcome the lack of biocompatibility issues, but the grafting process should have a minimal impact on the surface’s properties. The tensile strength and swelling tests showed no apparent modification before and after grafting in crosslinking densities and elasticity moduli. That confirms the impactless aspect of the grafting protocol on the material’s mechanical properties. Surface roughness was investigated by atomic force microscopy to understand cell behavior on surfaces upon various treatments. Biocompatibility tests showed that the grafting of polyNaSS significantly enhanced cell adhesion and viability compared to a non grafted silicone. Overall, polyNaSS confers a highly suitable surface for fibroblasts, demonstrating their active forms (spindle-shaped). This was assessed by optical microscopy, scanning electron microscopy, and atomic force microscopy.

Biological properties of direct grafting by ultraviolet irradiation of vinyl benzyl phosphonic acid onto titanium surfaces

Titanium (Ti) and its alloys are the most effective metals for structural implantable device applications. However, Ti-based materials are passively integrated into the bone, resulting in a purely mechanical attachment. Consequently, the loss of osseointegration often leads to implant failure. Therefore, enhancing bone formation surrounding the implant is primordial. In previous investigations conducted in our laboratory, grafting bioactive polymers with sulfonate groups, such as poly(sodium styrene sulfonate) (polyNaSS), was demonstrated to increase the adherence and differentiation of osteoblast cells. In this context, this contribution proposes to functionalize Ti with a phosphonic acid-based polymer, poly(vinyl benzyl phosphonic acid) (poly(VBP)). A two-step UV-initiated grafting polymerization was developed to covalently graft VBP into Ti surfaces. The surfaces were characterized using colorimetry, Fourier-transformed infrared spectra recorded in an attenuated total reflection (FTIR-ATR), X-ray photoelectron spectroscopy (XPS) techniques, and water contact angle (WCA) measurements. The Ti substrates were evaluated for cell viability, spreading, alkaline phosphatase activity, and calcium formation using MC3T3-E1 osteoblast cells. The interaction of Ti grafted samples with osteoblast cells, was significantly improved as well as the cell/surface interaction. Together, these findings demonstrated that poly(VBP) grafted on Ti surfaces improved osteoblasts' early cell adhesion and spreading activities, crucial for osseointegration applications.

Fabrication of Biohybrid Nanofibers by the Green Electrospinning Technique and Their Antibacterial Activity.

The development of bioactive polymer nanofiber sheets based on eco-friendly components is required to meet the needs of various medical applications as well as to preserve the environment. This study aimed to fabricate biohybrid nanofibers based on water-soluble polymers and aqueous extract of myrrh. The myrrh extract was incorporated into poly(vinyl alcohol)/tragacanth gum nanofiber mats (myrrh@PVA/TG) by the green electrospinning technique. Various characteristics of the prepared fibers such as morphology, fiber diameter distribution, crystallinity, and thermal stability were studied. The results confirmed that the morphology of biohybrid nanofibers was uniform without beads and tragacanth gum plays an important role in controlling the average diameter of fibers and the crystallinity. The antibacterial properties of the developed biohybrid nanofibers were investigated against common pathogens of Gram-positive and Gram-negative bacteria by the standard disc diffusion method. A significant antibacterial activity was observed toward bacterial strains after incorporation of aqueous myrrh extract into nanofibers, which increased on increasing the extract ratio. Due to their eco-friendly components and significant antibacterial activity, the prepared biohybrid nanofibers will open new avenues toward incorporating aqueous herbal extracts into degradable polymer fibers for use in many antibacterial applications.

Synthesis of Star 6-Arm Polyethylene Glycol-Heparin Copolymer to Construct Anticorrosive and Biocompatible Coating on Magnesium Alloy Surface.

Magnesium alloy has become a research hotspot of the degradable vascular stent materials due to its biodegradability and excellent mechanical properties. However, its rapid degradation rate after implantation and the limited biocompatibility restrict its application in clinic. Constructing a multifunctional bioactive polymer coating on the magnesium alloys represents one of the popular and effective approaches to simultaneously improve the corrosion resistance and biocompatibility. In the present study, the copolymer of 6-arm polyethylene glycol and heparin (PEG-Hep) was successfully synthesized and then immobilized on the surface of chitosan (Chi)-modified magnesium alloy surface through electrostatic interaction to improve the corrosion resistance and biocompatibility. The results of attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy showed that a dense and compact coating was created on the magnesium alloy surface. The coating displayed excellent hydrophilicity. At the same time, the as-prepared coating can significantly not only improve the corrosion potential, reduce the corrosion current and the pH changes of the immersion solution, but also keep a relatively intact surface morphology after immersing in simulated body fluid solution for 14 days, demonstrating that the coating can significantly improve the corrosion resistance of the magnesium alloy. Moreover, the magnesium alloy with PEG-Hep coating exhibited excellent hemocompatibility according to the results of the hemolysis rate and platelet adhesion and activation. In addition, the modified magnesium alloy had a good ability to promote the endothelial cell adhesion and proliferation. Therefore, the PEG-Hep multifunctional coating can be applied in the surface modification of the biodegradable magnesium alloy stent to simultaneously improve the corrosion resistance and biocompatibility.

Bioactive Graphene Quantum Dots Based Polymer Composite for Biomedical Applications.

Today, nanomedicine seeks to develop new polymer composites to overcome current problems in diagnosing and treating common diseases, especially cancer. To achieve this goal, research on polymer composites has expanded so that, in recent years, interdisciplinary collaborations between scientists have been expanding day by day. The synthesis and applications of bioactive GQD-based polymer composites have been investigated in medicine and biomedicine. Bioactive GQD-based polymer composites have a special role as drug delivery carriers. Bioactive GQDs are one of the newcomers to the list of carbon-based nanomaterials. In addition, the antibacterial and anti-diabetic potentials of bioactive GQDs are already known. Due to their highly specific surface properties, π-π aggregation, and hydrophobic interactions, bioactive GQD-based polymer composites have a high drug loading capacity, and, in case of proper correction, can be used as an excellent option for the release of anticancer drugs, gene carriers, biosensors, bioimaging, antibacterial applications, cell culture, and tissue engineering. In this paper, we summarize recent advances in using bioactive GQD-based polymer composites in drug delivery, gene delivery, thermal therapy, thermodynamic therapy, bioimaging, tissue engineering, bioactive GQD synthesis, and GQD green resuscitation, in addition to examining GQD-based polymer composites.

The effect of pNaSS grafting of knitted poly(ε-caprolactone) artificial ligaments on in vitro mineralization and in vivo osseointegration

Augmenting anterior cruciate ligament (ACL) repair using synthetic scaffolds to promote ligament healing is a new emerging surgical strategy for the treatment of ruptured ACL. Osseointegration of such scaffolds is critical, as the lack of osseointegration may lead to bone tunnel widening and joint instability.This study aimed to evaluate osseointegration of a new poly(ε-caprolactone) (PCL)-knitted artificial ligament and the potential benefits of its functionalization with the grafting of a bioactive polymer, the polystyrene sodium sulfonate (pNaSS), on bone incorporation.In vitro assays showed that the functionalization of PCL substrates positively impacted pre-osteoblasts proliferation and differentiation through superior alkaline phosphatase activity and higher calcium deposition. Implantation of pNaSS-grafted PCL ligaments for 12 weeks in a rat model of ACL repair augmentation, using non-grafted PCL ligaments and tendinous autograft as control conditions, showed enhanced osseointegration of autografts and grafted PCL ligaments compared to non-grafted ligaments. These results open up new avenues to improve osseointegration of PCL ligaments designed for ACL repair.

Bioactive Monomer and Polymer Polyketides from Edible Mushroom Cortinarius caerulescens as Glutamate Dehydrogenase Inhibitors and Antioxidants.

Two new polyketides named rufoolivacin E and viocristin B, a new natural product named 1-hydroxy-3,6,8-trimethoxyanthraquinone, and 13 known compounds were isolated from edible mushroom Cortinarius purpurascens in this work. Their structures were assigned on the basis of high-resolution electrospray ionization mass spectrometry, 1D and 2D nuclear magnetic resonance, and electronic circular dichroism data. Notably, the enzyme activity test on glutamate dehydrogenase indicated that 1, 3, 4, 5, 6, 10, 11, and 15 displayed an excellent inhibition effect. Further kinetic studies showed that the most potent compounds, 4 and 10, possess great potential as competitive inhibitors of glutamate dehydrogenase. Molecular docking and computational chemistry were applied to illustrate the binding mechanism in detail. 2,2-Diphenyl-1-picrylhydrazyl and reactive oxygen species assay results showed that compounds 1, 2, 3, and 8 exhibited significant antioxidant activities with IC50 values of 7.0 ± 0.3, 8.6 ± 0.1, 7.5 ± 0.1, and 2.8 ± 0.2 μg mL-1, respectively. Thus, Cortinarius caerulescens represents a novel resource of these polyketides to be utilized in food selection and drug discovery.