A Family of Hexacopper Phenylsilsesquioxane/Acetate Complexes: Synthesis, Solvent-Controlled Cage Structures, and Catalytic Activity.

Convenient self-assembly synthesis of copper(II) complexes via double (phenylsilsesquioxane and acetate) ligation allows to isolate a family of impressive sandwich-like cage compounds. An intriguing feature of these complexes is the difference in the structure of a pair of silsesquioxane ligands despite identical (Cu6) nuclearity and number (four) of acetate fragments. Formation of particular combination of silsesquioxane ligands (cyclic/cyclic vs condensed/condensed vs cyclic/condensed) was found to be dependent on the synthesis/crystallization media. A combination of Si4-cyclic and Si6-condensed silsesquioxane ligands is a brand new feature of cage metallasilsesquioxanes. A representative Cu6-complex (4) (with cyclic silsesquioxanes) exhibited high catalytic activity in the oxidation of alkanes and alcohols with peroxides. Maximum yield of the products of cyclohexane oxidation attained 30 %. The compound 4 was also tested as catalyst in the Baeyer-Villiger oxidation of cyclohexanone by m-chloroperoxybenzoic acid: maximum yields of 88 % and 100 % of ϵ-caprolactone were achieved upon conventional heating at 50 °C for 4 h and MW irradiation at 70 or 80 °C during 30 min, respectively. It was also possible to obtain the lactone (up to 16 % yield) directly from the cyclohexane via a tandem oxidation/Baeyer-Villiger oxidation reaction using the same oxidant.

Mechanical and biological properties of poly-ε-caprolactone membrane for pleurodesis: A preclinical study in pigs.

BACKGROUND/PURPOSE: Biomaterial implants are emerging as a treatment choice for pleurodesis; however, the optimal biomaterial and form for managing spontaneous pneumothorax, particularly post-video-assisted thoracic surgery, remain under investigation. This study evaluated the mechanical and biological properties of the poly-ε-caprolactone (PCL) membrane as a sclerosing agent for pleurodesis in Landrace pigs. METHODS: Twenty-four Landrace pigs were split into two groups for mechanical abrasion and PCL membrane pleurodesis, with the latter group's PCL meshes inserted using video-assisted thoracic surgery. The mechanical and biological properties of the PCL membrane were assessed in pigs at three, six, and 12 months after the procedure. This assessment involved a range of techniques, such as the T-Peel test, macroscopic evaluation with a scoring scale, microscopic examination, and biomechanical and molecular weight analysis. RESULTS: The PCL membrane group outperformed the traditional abrasion group, with stronger adhesions seen over longer implantation durations. This group also showed superior and more consistent results in both macroscopic and microscopic evaluations compared to the control group. The membrane-based method was easier and faster to perform than the control group's method, and importantly, no mortality occurred following membrane implantation. CONCLUSION: This study is the pioneering effort to present long-term findings regarding the mechanical and biological properties of the PCL membrane in an in vivo animal model. The membrane demonstrated better adhesion ability than that of traditional abrasion and showed reassuring biocompatibility in both the pig model, suggesting its potential as treatment for patients with primary spontaneous pneumothorax. Further clinical studies are needed to support these observations.

Is Silver Addition to Scaffolds Based on Polycaprolactone Blended with Calcium Phosphates Able to Inhibit Candida albicans and Candida auris Adhesion and Biofilm Formation?

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.

In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams.

Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F + coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.Scaffolds did not affect mice weight development and organs, indicating no organ toxicity. Moreover, scaffolds maintained their size and shape and reflected a high cell viability prior to and following implantation. Coll or F + coll scaffolds seeded with cells yielded superior macroscopic properties compared to the controls. Mild signs of inflammation (foreign-body giant cells and hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable after explantation, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in explanted scaffolds compared to those before implantation, with no significant differences between scaffold subtypes, except for a higher maximum force in F + coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. a Lapine anterior cruciate ligament (LACL): red arrow, posterior cruciate ligament: yellow arrow. Medial anterior meniscotibial ligament: black arrow. b Explant culture to isolate LACL fibroblasts. c Scaffold variants: co: controls; F: functionalization by gas-phase fluorination; coll: collagen foam cross-linked with hexamethylene diisocyanate (HMDI). c1-2 Embroidery pattern of the scaffolds. d Scaffolds were seeded with LACL fibroblasts using a dynamical culturing approach as depicted. e Scaffolds were implanted subnuchally into nude mice, fixed at the nuchal ligament and sacrospinal muscle tendons. f Two weeks after implantation. g Summary of analyses performed. Scale bars 1 cm (b, d), 0.5 cm (c). (sketches drawn by G.S.-T. using Krita 4.1.7 [Krita foundation, The Netherlands]).

UV-Blocking and Light-Responsive Poly (ϵ-Caprolactone)/ZIF-8 Multifunctional Composite Films for Efficient Antibacterial Activities.

Antibacterial photodynamic therapy (APDT) has received considerable attention owing to its superiority. ZIF-8 was used to address the poor stability of the photosensitizer Rose Bengal (RB) encapsulation to synthesize RB@ZIF-8 NPs, which were doped into a composite film with poly (ϵ-caprolactone) (PCL) and polyvinyl alcohol-quaternary ammonium chitosan (PVA-QCS) as substrates to form composite films (PQZ). The composite films exhibited excellent photodynamic sterilization and good resistance to bacterial adhesion. The tensile strength of the film increased to 43.4 MPa, which was approximately 1.8 times that of the PCL film. With the addition of SiO2 and RB@ZIF-8 NPs, the film exhibited water repellency and UV-blocking properties. RAW264.7 cells were selected using the MTT method to confirm that the composite films had excellent biocompatibility and had no significant inhibitory effect on cell growth and reproduction. PQZ multifunctional composite films show potential as novel APDT antimicrobial materials for food packaging.

Nanofibrous polycaprolactone/gelatin scaffold containing gold nanoparticles: Physicochemical and biological characterization for wound healing.

In this study, gold nanoparticles were loaded into poly (ε-caprolactone) (PCL)/gelatin nanofibrous matrices to fabricate a potential wound dressing. The mats were produced by electrospinning of PCL/gelatin solution supplemented with synthesized gold nanoparticles (200, 400 and 800 ppm). Prepared scaffolds were investigated regarding their chemical properties, morphology, mechanical properties, surface wettability, water-uptake capacity, water vapor permeability, porosity, blood compatibility, microbial penetration test and cellular response. In addition to in vivo study, a full-thickness excisional wound in a rat model was used to evaluate the healing effect of prepared scaffolds. Results showed appropriate mechanical properties and porosity of prepared scaffolds. With L929 cells, the PCL/gelatin scaffold containing 400 ppm gold nanoparticles demonstrated the greatest cell growth. In vivo results validated the favorable wound-healing benefits of the scaffold incorporating gold nanoparticles, which triggered wound healing compared to sterile gauze. Our results showed the capability of nanofibrous matrices containing gold nanoparticles for successful wound treatment.

Synthesis of a New Poly(ε-caprolactone)-g-Chitosan Amphiphilic Graft Copolymer with a "Reverse" Structure.

Hydrophilic chitosan (CHT) and hydrophobic polyε-caprolactone (PCL) are well-known biocompatible and biodegradable polymers that have many applications in the biomedical and pharmaceutical fields. But the mixtures of these two compounds are considered incompatible, which makes them not very interesting. To avoid this problem and to further extend the properties of these homopolymers, the synthesis of a new graft copolymer, the fully biodegradable amphiphilic poly(ε-caprolactone-g-chitosan) (PCL-g-CHT) is described, with an unusual "reverse" structure formed by a PCL backbone with CHT grafts, unlike the "classic" CHT-g-PCL structure with a CHT main chain and PCL grafts. This copolymer is prepared via a copper-catalyzed 1,3-dipolar Huisgen cycloaddition between propargylated PCL (PCL-yne) and a new azido-chitosan (CHT-N3 ). In order to obtain an amphiphilic copolymer regardless of the pH, chitosan oligomers, soluble at any pH, are prepared and used. The amphiphilic PCL-g-CHT copolymer spontaneously self-assembles in water into nanomicelles that may incorporate hydrophobic drugs to give novel drug delivery systems.

Multi-stimuli-responsive chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles as theranostic platforms for combined tumor magnetic resonance imaging and chemotherapy.

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors.

Development of a porous layer-by-layer microsphere with branched aliphatic hydrocarbon porogens.

Porous polymer microspheres are employed in biotherapeutics, tissue engineering, and regenerative medicine. Porosity dictates cargo carriage and release that are aligned with the polymer physicochemical properties. These include material tuning, biodegradation, and cargo encapsulation. How uniformity of pore size affects therapeutic delivery remains an area of active investigation. Herein, we characterize six branched aliphatic hydrocarbon-based porogen(s) produced to create pores in single and multilayered microspheres. The porogens are composed of biocompatible polycaprolactone, poly(lactic-co-glycolic acid), and polylactic acid polymers within porous multilayered microspheres. These serve as controlled effective drug and vaccine delivery platforms.

Silica Aerogel-Polycaprolactone Scaffolds for Bone Tissue Engineering.

Silica aerogel is a material composed of SiO2 that has exceptional physical properties when utilized for tissue engineering applications. Poly-ε-caprolactone (PCL) is a biodegradable polyester that has been widely used for biomedical applications, namely as sutures, drug carriers, and implantable scaffolds. Herein, a hybrid composite of silica aerogel, prepared with two different silica precursors, tetraethoxysilane (TEOS) or methyltrimethoxysilane (MTMS), and PCL was synthesized to fulfil bone regeneration requirements. The developed porous hybrid biocomposite scaffolds were extensively characterized, regarding their physical, morphological, and mechanical features. The results showed that their properties were relevant, leading to composites with different properties. The water absorption capacity and mass loss were evaluated as well as the influence of the different hybrid scaffolds on osteoblasts' viability and morphology. Both hybrid scaffolds showed a hydrophobic character (with water contact angles higher than 90°), low swelling (maximum of 14%), and low mass loss (1-7%). hOB cells exposed to the different silica aerogel-PCL scaffolds remained highly viable, even for long periods of incubation (7 days). Considering the obtained results, the produced hybrid scaffolds may be good candidates for future application in bone tissue engineering.

Polymer-Degrading Enzymes of Pseudomonas chloroaphis PA23 Display Broad Substrate Preferences.

Although many bacterial lipases and PHA depolymerases have been identified, cloned, and characterized, there is very little information on the potential application of lipases and PHA depolymerases, especially intracellular enzymes, for the degradation of polyester polymers/plastics. We identified genes encoding an intracellular lipase (LIP3), an extracellular lipase (LIP4), and an intracellular PHA depolymerase (PhaZ) in the genome of the bacterium Pseudomonas chlororaphis PA23. We cloned these genes into Escherichia coli and then expressed, purified, and characterized the biochemistry and substrate preferences of the enzymes they encode. Our data suggest that the LIP3, LIP4, and PhaZ enzymes differ significantly in their biochemical and biophysical properties, structural-folding characteristics, and the absence or presence of a lid domain. Despite their different properties, the enzymes exhibited broad substrate specificity and were able to hydrolyze both short- and medium-chain length polyhydroxyalkanoates (PHAs), para-nitrophenyl (pNP) alkanoates, and polylactic acid (PLA). Gel Permeation Chromatography (GPC) analyses of the polymers treated with LIP3, LIP4, and PhaZ revealed significant degradation of both the biodegradable as well as the synthetic polymers poly(ε-caprolactone) (PCL) and polyethylene succinate (PES).

Dispersant and Protective Roles of Amphiphilic Poly(ethylene phosphate) Block Copolymers in Polyester/Bone Mineral Composites.

Composites of synthetic bone mineral substitutes (BMS) and biodegradable polyesters are of particular interest for bone surgery and orthopedics. Manufacturing of composite scaffolds commonly uses mixing of the BMS with polymer melts. Melt processing requires a high homogeneity of the mixing, and is complicated by BMS-promoted thermal degradation of polymers. In our work, poly(L-lactide) (PLLA) and poly(ε-caprolactone) (PCL) composites reinforced by commercial ß-tricalcium phosphate (ßTCP) or synthesized carbonated hydroxyapatite with hexagonal and plate-like crystallite shapes (hCAp and pCAp, respectively) were fabricated using injection molding. pCAp-based composites showed advanced mechanical and thermal characteristics, and the best set of mechanical characteristics was observed for the PLLA-based composite containing 25 wt% of pCAp. To achieve compatibility of polyesters and pCAp, reactive block copolymers of PLLA or PCL with poly(tert-butyl ethylene phosphate) (C1 and C2, respectively) were introduced to the composite. The formation of a polyester-b-poly(ethylene phosphoric acid) (PEPA) compatibilizer during composite preparation, followed by chemical binding of PEPA with pCAp, have been proved experimentally. The presence of 5 wt% of the compatibilizer provided deeper homogenization of the composite, resulting in a marked increase in strength and moduli as well as a more pronounced nucleation effect during isothermal crystallization. The use of C1 increased the thermal stability of the PLLA-based composite, containing 25 wt% of pCAp. In view of positive impacts of polyester-b-PEPA on composite homogeneity, mechanical characteristics, and thermal stability, polyester-b-PEPA will find application in the further development of composite materials for bone surgery and orthopedics.

Co-Culture of Mesenchymal Stem Cells and Ligamentocytes on Triphasic Embroidered Poly(L-lactide-co-ε-caprolactone) and Polylactic Acid Scaffolds for Anterior Cruciate Ligament Enthesis Tissue Engineering.

Successful anterior cruciate ligament (ACL) reconstructions strive for a firm bone-ligament integration. With the aim to establish an enthesis-like construct, embroidered functionalized scaffolds were colonized with spheroids of osteogenically differentiated human mesenchymal stem cells (hMSCs) and lapine (l) ACL fibroblasts in this study. These triphasic poly(L-lactide-co-ε-caprolactone) and polylactic acid (P(LA-CL)/PLA) scaffolds with a bone-, a fibrocartilage transition- and a ligament zone were colonized with spheroids directly after assembly (DC) or with 14-day pre-cultured lACL fibroblast and 14-day osteogenically differentiated hMSCs spheroids (=longer pre-cultivation, LC). The scaffolds with co-cultures were cultured for 14 days. Cell vitality, DNA and sulfated glycosaminoglycan (sGAG) contents were determined. The relative gene expressions of collagen types I and X, Mohawk, Tenascin C and runt-related protein (RUNX) 2 were analyzed. Compared to the lACL spheroids, those with hMSCs adhered more rapidly. Vimentin and collagen type I immunoreactivity were mainly detected in the hMSCs colonizing the bone zone. The DNA content was higher in the DC than in LC whereas the sGAG content was higher in LC. The gene expression of ECM components and transcription factors depended on cell type and pre-culturing condition. Zonal colonization of triphasic scaffolds using spheroids is possible, offering a novel approach for enthesis tissue engineering.

Titanium and Vanadium Complexes of Tridentate Phenoxy-Imine and Phenoxy-Amine Ligands and Their Application in the Ring-Opening Polymerization of Cyclic Esters.

Phenoxy-imine and phenoxy-amine proligands, with the additional OH donor groups 2,4-tBu2-6-(2-CH2(OH)-C6H4N=CH)C6H3OH (L1H2), 6-(2-CH2(OH)-C6H4N=CH)C6H3OH (L2H2), and 2,4-tBu2-6-(2-CH2(OH)-C6H4NH-CH)C6H3OH (L3H2), were synthesized and their titanium (Ti-L1-Ti-L3) and vanadium (V-L1-V-L2) complexes were prepared in reactions with Ti(OiPr)4 and VO(OiPr)3, respectively. All new compounds were characterized with the use of FTIR, 1H, and 13C NMR spectroscopy; X-ray crystallography was also used to study proligands. All the complexes proved to be active catalysts in the ring-opening polymerization (ROP) of ε-caprolactone, rac-lactide, and L-lactide in the melt. The effects of the complex structure (transition metal type, presence of tBu substituents, and type of nitrogen donor group), as well as the polymerization time and temperature, on the monomer conversion and polymer properties were investigated in detail.

Protection and Disinfection Activities of Oregano and Thyme Essential Oils Encapsulated in Poly(ε-caprolactone) Nanocapsules.

The biocolonization of building materials by microorganisms is one of the main causes of their degradation. Fungi and bacteria products can have an undesirable impact on human health. The protection and disinfection of sandstone and wood materials are of great interest. In this study, we evaluated the protection and disinfection activity of oregano and thyme essential oils encapsulated in poly(ε-caprolactone) nanocapsules (Or-NCs, Th-NCs) against four types of environmental microorganisms: Pleurotus eryngii, Purpureocillium lilacinum (fungal strains), Pseudomonas vancouverensis, and Flavobacterium sp. (bacterial strains). The surfaces of sandstone and whitewood samples were inoculated with these microorganisms before or after applying Or-NCs and Th-NCs. The concentration-dependent effect of Or-NCs and Th-NCs on biofilm viability was determined by the MTT reduction assay. The results showed that Or-NCs and Th-NCs possess effective disinfection and anti-biofilm activity. Diffuse reflectivity measurements revealed no visible color changes of the materials after the application of the nanoencapsulated essential oils.

Chitosan functionalized PCL nanoparticles bearing tyrosine kinase inhibitor osimertinib mesylate for effective lung cancer therapy.

Lung cancer ranks second position among the cancer-related deaths. Osimertinib mesylate (OSM) is a tyrosine-kinase-inhibitor which can effectively treat non-small cell lung cancer (NSCLC), but still there are certain limitations and side effects which could be circumvented by polymeric nanoparticles approach. Hence, this research was aimed to develop drug-loaded biodegradable polycaprolactone nanoparticles (PCL-NPs) such as OSM-loaded PCL-NPs (PCL-OSM-NPs) and chitosan fabricated OSM-loaded PCL-NPs (CS-PCL-OSM-NPs) to achieve active-targeting of OSM in the cancerous lung tissue. Thus, CS-PCL-OSM-NPs enhance the anticancer efficacy due to active targeting nature and thereby reduces off-target side effects of OSM in the NSCLC treatment. Blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs were prepared by nanoprecipitation method. Optimized blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs exhibited the mean particle size of 90.2 ± 4.7 nm, 167.7 ± 2.9 nm, and 233.7 ± 4.8 nm respectively. The encapsulation efficiency % (%EE) of PCL-OSM-NPs was found to be 68.4 ± 3.2%. In vitro drug release study demonstrated sustained release profile of 69.5 ± 5% and 65.7 ± 1.5% for OSM from both the PCL-OSM-NPs and CS-PCL-OSM-NPs, respectively. The PCL-OSM-NPs and CS-PCL-OSM-NPs demonstrated the inhibition of 82.2 ± 0.5% and 81.9 ± 0.2% in A549 cancer cells respectively which clearly signified the improved efficacy. Moreover, the PCL-OSM-NPs and CS-PCL-OSM-NPs exhibited significantly less hemolysis than OSM indicating safety of the formulation. These findings indicate that biohemocompatible CS-PCL-OSM-NPs is an attractive option to treat NSCLC with enhanced anticancer activity and reduced side effects.

Versatile aliphatic polyester biosynthesis system for producing random and block copolymers composed of 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates using the sequence-regulating polyhydroxyalkanoate synthase PhaCAR.

BACKGROUND: Polyhydroxyalkanoates (PHAs) are microbial polyesters synthesized by PHA synthases. Naturally occurring PHA copolymers possess a random monomer sequence. The development of PhaCAR, a unique sequence-regulating PHA synthase, has enabled the spontaneous biosynthesis of PHA block copolymers. PhaCAR synthesizes both a block copolymer poly(2-hydroxybutyrate)-b-poly(3-hydroxybutyrate) [P(2HB)-b-P(3HB)], and a random copolymer, poly(3HB-co-3-hydroxyhexanoate), indicating that the combination of monomers determines the monomer sequence. Therefore, in this study, we explored the substrate scope of PhaCAR and the monomer sequences of the resulting copolymers to identify the determinants of the monomer sequence. PhaCAR is a class I PHA synthase that is thought to incorporate long-main-chain hydroxyalkanoates (LMC HAs, > C3 in the main [backbone] chain). Thus, the LMC monomers, 4-hydroxy-2-methylbutyrate (4H2MB), 5-hydroxyvalerate (5HV), and 6-hydroxyhexanoate (6HHx), as well as 2HB, 3HB, and 3-hydroxypropionate (3HP) were tested. RESULTS: Recombinant Escherichia coli harboring PhaCAR, CoA transferase and CoA ligase genes was used for PHA production. The medium contained the monomer precursors, 2HB, 3HB, 3HP, 4H2MB, 5HV, and 6HHx, either individually or in combination. As a result, homopolymers were obtained only for 3HB and 3HP. Moreover, 3HB and 3HP were randomly copolymerized by PhaCAR. 3HB-based binary copolymers P(3HB-co-LMC HA)s containing up to 2.9 mol% 4H2MB, 4.8 mol% 5HV, or 1.8 mol% 6HHx were produced. Differential scanning calorimetry analysis of the copolymers indicated that P(3HB-co-LMC HA)s had a random sequence. In contrast, combining 3HP and 2HB induced the synthesis of P(3HP)-b-P(2HB). Similarly, P(2HB) segment-containing block copolymers P(3HB-co-LMC HA)-b-P(2HB)s were synthesized. Binary copolymers of LMC HAs and 2HB were not obtained, indicating that the 3HB or 3HP unit is essential to the polymer synthesis. CONCLUSION: PhaCAR possesses a wide substrate scope towards 2-, 3-, 4-, 5-, and 6-hydroxyalkanoates. 3HB or 3HP units are essential for polymer synthesis using PhaCAR. The presence of a 2HB monomer is key to synthesizing block copolymers, such as P(3HP)-b-P(2HB) and P(3HB-co-LMC HA)-b-P(2HB)s. The copolymers that did not contain 2HB units had a random sequence. This study's results provide insights into the mechanism of sequence regulation by PhaCAR and pave the way for designing PHA block copolymers.

Molecular docking studies of YKT tripeptide and drug delivery system with poly(ε-caprolactone) nanoparticles.

Tyrosyllysylthreonine (YKT) is a peptide structure that contains three different amino acids in its structure and has anticancer properties. The main purpose of this study is to reveal the structural interactions of the peptide and to increase the efficiency of the peptide with nanoformulation. For these purposes, YKT-loaded poly(ε-caprolactone) (PCL) nanoparticles (NPs) were synthesized using the double-emission precipitation method and the obtained NPs were characterized with a Zeta Sizer, UV-Vis, Fourier transform infrared-attenuated total reflection spectrometers, scanning electron microscopy, and transmission electron microscopy. The in vitro release profile of the peptide-loaded PCL NPs was determined. In molecular modeling studies, PCL, PCL-polyvinyl alcohol (PVA), and PCL-PVA-YKT systems were simulated in an aqueous medium by molecular dynamics simulations, separately. The information about the interactions between the YKT tripeptide and the epidermal growth factor and androgen, estrogen, and progesterone receptors were obtained with the molecular docking study. Additionally, the ADME profile of YKT was determined as a result of each docking study. In conclusion, tripeptide-based nanodrug development studies of the YKT tripeptide are presented in this study.

Enhancing osteoblast differentiation through small molecule-incorporated engineered nanofibrous scaffold.

OBJECTIVE: This study aimed to investigate the effect of small molecules incorporated into the engineered nanofibrous scaffold to enhance the osteoblast differentiation MATERIALS AND METHODS: Poly-ε-caprolactone (PCL) nanofiber matrices with lithium chloride (LiCl) were fabricated using the electrospinning technique. Scaffolds were characterized using scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). Scaffolds were seeded with MC3T3-E1 cells and assessed using Western blots (ß-catenin), alamarBlue assay (proliferation), qPCR (osteoblast differentiation), and mineralization (Alizarin Red staining). RESULTS: We observed LiCl nanofiber scaffolds induced concentration-dependent cell proliferation that correlated with an increased ß-catenin expression indicating sustained Wnt signaling. Next, we examined osteoblast differentiation markers such as osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) and noted increased expression in LiCl nanofiber scaffolds. We also noted increased bone morphogenetic protein (BMP-2, 4, and 7) expressions suggesting activated Wnt can promote cures to further osteogenic differentiation. Finally, Alizarin Red staining demonstrated increased mineral deposition in LiCl-incorporated nanofiber scaffolds. CONCLUSIONS: Together, these results indicated that LiCl-incorporated nanofiber scaffolds enhance osteoblast differentiation. CLINICAL RELEVANCE: Small molecule-incorporated nanofibrous scaffolds are an innovative clinical tool for bone tissue engineering.

Sirolimus-exuding core-shell nanofibers as an implantable carrier for breast cancer therapy: preparation, characterization, in vitro cell studies, and in vivo anti-tumor activity.

OBJECTIVE: Breast cancer accounts for significant mortality worldwide. Here, we develop a localized, sustained-release delivery system for breast cancer therapy. METHODS: Sirolimus (SIR) core-shell nanofibers (NFs) are fabricated by coaxial electrospinning with poly(ε-caprolactone) (PCL) for the core and chitosan and PCL for the shell. The NFs were characterized by SEM, AFM, TEM, XRD, FTIR, water uptake, water contact angle, mechanical properties, drug content, and in vitro release. In vitro and in vivo anticancer effects were investigated. RESULTS: A sustained release behavior is observed during 480 h that is more extended compared to monoaxial NFs. In vitro cytotoxicity and Annexin V/propidium iodide assays indicate that SIR-loaded coaxial NFs are effective in inhibiting proliferation of 4T1 and MCF-7 cells. Implantation of SIR NFs in 4T1 breast tumor-bearing mice inhibits tumor growth significantly compared to free drug. Histopathological examination shows that suppression of tumor growth by SIR NFs is associated with apoptotic cell death. Furthermore, anti-cancer effects are also confirmed by decreased expression levels of Ki-67, MMP-2, and MMP-9. Histological observation of organs, serological analyses, and the lack of body weight changes indicate in vivo safety of SIR NFs. CONCLUSIONS: Altogether, we show here that incorporation of SIR into core-shell NFs could act as an effective drug release depot and induce a sustained antitumor response.