Search Results (30)

Triple-negative breast cancer (TNBC) frequently evades immune recognition and elimination, resulting in an immunosuppressive microenvironment. The phagocytic activity of tumor-associated macrophages underscores the development of nanomaterials as a promising strategy to target these macrophages and modulate their polarization, thereby advancing immunotherapy against TNBC. This research developed functional polymers that are complexed with therapeutic molecules as a coating strategy for iron oxide nanoparticles. An arginine-based poly (ester urea urethane) polymer complexed with a macrophage-polarizing molecule (APU-R848) could provide a synergistic effect with iron oxide nanoparticles (IONPs) to stimulate the M1-polarization of macrophages at the tumor site, resulting in a versatile nano-platform for immune regulation of TNBC. In the 4T1 in vivo breast tumor model, the APU-R848-IONPs demonstrated an improved intratumoral biodistribution compared to IONPs without a polymer coating. APU-R848-IONPs significantly reversed the immune-suppressive tumor environment by reducing the M2/M1 macrophage phenotype ratio by 51%, associated with an elevated population of cytotoxic T cells and a significantly enhanced production of tumoricidal cytokines. The activated immune response induced by APU-R848-IONP resulted in a significant anti-tumor effect, demonstrating an efficacy that was more than 3.2-fold more efficient compared to the controls. These immune-regulatory pseudo-protein-coated iron oxide nanoparticles represent an effective nano-strategy for macrophages’ regulation and the activation of anti-tumor immunity, providing a new treatment modality for triple-negative breast cancer. Full article

Aliphatic unsegmented polyurethanes (PUs) have garnered relatively limited attention in the literature, despite their valuable properties such as UV resistance and biocompatibility, making them suitable for biomedical applications. This study focuses on synthesizing poly(ester-urethanes) (PEUs) using 1,6-hexamethylene diisocyanate and the macrodiol α,ω-hydroxy telechelic poly(ε-caprolactone) (HOPCLOH). To optimize the synthesis, a statistical experimental design approach was employed, a methodology not commonly utilized in polymer science. The influence of reaction temperature, time, reagent concentrations, and solvent type on the resulting PEUs was investigated. Characterization techniques included FT-IR, ¹H NMR, differential scanning calorimetry (DSC), gel permeation chromatography (GPC), optical microscopy, and mechanical testing. The results demonstrated that all factors significantly impacted the number-average molecular weight (M_n) as determined by GPC. Furthermore, the statistical design revealed crucial interaction effects between factors, such as a dependence between reaction time and temperature. For example, a fixed reaction time of 1 h, with the temperature varying from 50 °C to 61° C, did not significantly alter M_n. Better reaction conditions yielded high M_n (average: 162,000 g/mol), desirable mechanical properties (elongation at break > 1000%), low levels of unreacted HOPCLOH in the PEU films (OH/ESTER response = 0.0008), and reduced crystallinity (ΔH_m = 11 J/g) in the soft segment, as observed by DSC and optical microscopy. In contrast, suboptimal conditions resulted in low M_n, brittle materials with unmeasurable mechanical properties, high crystallinity, and significant amounts of residual HOPCLOH. The best experimental conditions were 61 °C, 0.176 molal, 8 h, and chloroform as the solvent (ε = 4.8). Full article

Background and objectives: The use of polymeric nanoparticles (NPs) in drug delivery systems offers the advantages of enhancing drug efficacy and minimizing side effects; Methods: In this study, L-threonine polyurethane (LTPU) NPs have been fabricated by water-in-oil-in-water emulsion and solvent evaporation using biodegradable and biocompatible LTPU. This polymer was pre-synthesized through the use of an amino acid-based chain extender, desaminotyrosyl L-threonine hexyl ester (DLTHE), where urethane bonds are formed by poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) triblock copolymer and 1,6-hexamethylene diisocyanate (HDI). LTPU is designed to be degraded by hydrolysis and enzymatic activity due to the presence of ester bonds and peptide bonds within the polymer backbone. LTPU NPs were fabricated by water-in-oil-in-water double emulsion solvent evaporation methods; Results: The polymerization of LTPU was confirmed by ¹H-NMR, ¹³C-NMR, and FT-IR spectroscopies. The molecular weights and polydispersity, determined with GPC, were 28,800 g/mol and 1.46, respectively. The morphology and size of NPs, characterized by DLS, FE-SEM, TEM, and confocal microscopy, showed smooth and spherical particles with diameters less than 200 nm; Conclusions: In addition, the drug loading, encapsulation efficiency, and drug release profiles, using UV-Vis spectroscopy, showed the highest encapsulation efficiency with 2.5% carboplatin and sustained release profile. Full article

Biodegradable polymers and bioceramics give rise to composite structures that serve as scaffolds to promote tissue regeneration. The current research explores the preparation of biodegradable filaments for additive manufacturing. Bioresorbable segmented poly(ester urethanes) (SPEUs) are easily printable elastomers but lack bioactivity and present low elastic modulus, making them unsuitable for applications such as bone tissue engineering. Strategies such as blending and composite filament production still constitute an important challenge in addressing SPEU limitations. In this work, SPEU-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blends and SPEU-PHBV-Bioglass 45S5^® (BG) composite materials were processed into filaments and 3D structures. A comprehensive characterization of their morphology and thermal and mechanical properties is presented. The production of 3D structures based on SPEU-PHBV with excellent dimensional precision was achieved. Although SPEU-PHBV-BG printed structures showed some defects associated with the printing process, the physicochemical, thermal, and mechanical properties of these materials hold promise. The blend composition, BG content and particle size, processing parameters, and blending techniques were carefully managed to ensure that the mechanical behavior of the material remained under control. The incorporation of PHBV in SPEU-PHBV at 70:30 w/w and BG (5 wt%) acted as reinforcement, enhancing both the elastic modulus of the filaments and the compressive mechanical behavior of the 3D matrices. The compressive stress of the printed scaffold was found to be 1.48 ± 0.13 MPa, which is optimal for tissues such as human proximal tibial trabecular bone. Therefore, these materials show potential for use in the design and manufacture of customized structures for bone tissue engineering. Full article

To develop an orthopedic scaffold that could overcome the limitations of implants used in clinics, we designed poly(ester-urethane) foams and compared their properties with those of a commercial gold standard. A degradable poly(ester-urethane) was synthetized by polyaddition between a diisocyanate poly(ε-caprolactone) prepolymer (PCL di-NCO, M_n = 2400 g·mol⁻¹) and poly(lactic-co-glycolic acid) diol (PLGA, M_n = 2200 g·mol⁻¹) acting as a chain extender. The resulting high-molecular-weight poly(ester-urethane) (PEU, M_n = 87,000 g·mol⁻¹) was obtained and thoroughly characterized by NMR, FTIR and SEC-MALS. The porous scaffolds were then processed using the solvent casting (SC)/particle leaching (PL) method with different NaCl crystal concentrations. The morphology, pore size and porosity of the foams were evaluated using SEM, showing interconnected pores with a uniform size of around 150 µm. The mechanical properties of the scaffolds are close to those of the human meniscus (Ey = 0.5~1 MPa). Their degradation under accelerated conditions confirms that incorporating PLGA into the scaffolds greatly accelerates their degradation rate compared to the gold-standard implant. Finally, a cytotoxicity study confirmed the absence of the cytotoxicity of the PEU, with a 90% viability of the L929 cells. These results suggest that degradable porous PLGA/PCL poly(ester-urethane) has potential in the development of meniscal implants. Full article

Tissue adhesives constitute a great possibility to improve conventional wound closure. In contrast to sutures, they enable nearly immediate hemostasis and can prevent fluid or air leaks. In the present study, a poly(ester)urethane-based adhesive was investigated which already proved to be suitable for different indications, such as reinforcing vascular anastomosis and sealing liver tissue. Using in vitro and in vivo setups, the degradation of the adhesives was monitored over a period of up to 2 years, to evaluate long-term biocompatibility and determine degradation kinetics. For the first time, the complete degradation of the adhesive was documented. In subcutaneous locations, tissue residues were found after 12 months and in intramuscular locations, tissue degradation was complete after about 6 months. A detailed histological evaluation of the local tissue reaction revealed good biocompatibility throughout the different degradation stages. After full degradation, complete remodeling to physiological tissue was observed at the implant locations. In addition, this study critically discusses common issues related to the assessment of biomaterial degradation kinetics in the context of medical device certification. This work highlighted the importance and encouraged the implementation of biologically relevant in vitro degradation models to replace animal studies or at least reduce the number of animals in preclinical testing prior to clinical studies. Moreover, the suitability of frequently used implantation studies based on ISO 10993-6 at standard locations was critically discussed, especially in light of the associated lack of reliable predictions for degradation kinetics at the clinically relevant site of implantation. Full article

The article below describes a simple methodology to prepare cost-effective biodegradable poly(ester urethane)s (PEUs) with ordered hard segments (OHS) for medical application as long-term implants. A low-cost diurethane diol (1,4-butanediol-hexanediisocyanate-1,4-butanediol, BHB) was first designed and synthesized. Consequently, the BHB was employed as a chain extender to react with NCO-terminated poly(ε-caprolactone) to obtain PEUs. The molecular structural formats for BHB and PEUs were defined through NMR, FT-IR, and MS together with GPC, while the influence of OHS content on physical/chemical features for casted PEU films was investigated. The introduction of OHS could contribute to forming denser hydrogen-bonds, and consequently produce a compact network structure, resulting in great tensile capacity, low water absorption, and slow hydrolytic degradation rate by PEU films. PEU-2.0 films, which possessed the highest OHS content within PEUs, exhibited 40.6 MPa tensile strength together with 477% elongation at break, 4.3 wt % equilibrium water absorption and only 29.5% weight loss post-12 months’ degradation. In addition, cytotoxicity analysis of film extracts indicated that the cell viability of all PEUs containing OHS exceeded 75%, indicating good cytocompatibility. Due to outstanding tensile features, high biostability, nontoxic and absorbable degradation products and acceptable cytocompatibility, the cost-effective materials exhibited promising applications in the field of long-term implants. Full article

A series of non-toxic biodegradable and biocompatible polyurethanes bearing p-aminobenzoate moieties are presented. The introduction of this attractive motif was carried out by the synthesis of a novel isocyanate. These biodegradable polymers were chemically and physically characterized by several techniques and methods including bioassay and water uptake measurements. The molecular weight of the soft segment (poly-ε-caprolactone, PCL) and hard segment crystallinity dictated the mechanical behavior and water uptake. The behavior of short PCL-based polyurethanes was elastomeric, whilst increasing the molecular weight of the soft segment led to plastic polyurethanes. Water uptake was hindered for long PCL due to the crystallization of the soft segment within the polyurethane matrix. Furthermore, two different types of chain extender, hydrolyzable and non-hydrolyzable, were also evaluated: polyurethanes based on hydrolyzable chain extenders reached higher molecular weights, thus leading to a better performance than their unhydrolyzable counterparts. The good cell adhesion and cytotoxicity results demonstrated the cell viability of human osteoblasts on the surfaces of these non-toxic biodegradable polyurethanes. Full article

Bio-based fillers for the polymer composites are still interesting from the scientific and industrial point of view, due to their low cost and renewable nature. In this work partially green composites were obtained by the mixing of thermoplastic poly(ester-urethane) with the unmodified and modified (by acetylation) grinded buckwheat husks. Obtained biocomposites were characterized in the terms of their chemical structure (FTIR), microstructure (SEM), thermal stability (TGA), thermomechanical properties (DMTA), and selected mechanical properties. The results showed that introduction of grinded buckwheat husks (even if the amount is 60 wt%) permit retaining high values of tensile strength (around 8–10 MPa), but the increasing amount of applied filler is connected with the decreasing of elongation at break. It can result from good interaction between the polymer matrix and the bio-based filler (confirmed by high values of polymer matrix-filler interaction parameter determined from Pukánszky’s model for the tensile strength of composites). The applied chemical treatment results in changing of mechanical properties of filler and composites. Obtained results confirmed the possibility of using powdered buckwheat husks as filler for thermoplastic polyurethane. Full article

This study concerns bio-based urethane prepolymers. The relationship between the chemical structure and the thermal and processing parameters of bio-based isocyanate-terminated ether and ester-urethane prepolymers was investigated. Bio-based prepolymers were obtained with the use of bio-monomers such as bio-based diisocyanate, bio-based polyether polyol or polyester polyols. In addition to their composition, the bio-based prepolymers were different in the content of iso-cyanate groups content (ca. 6 and 8%). The process of pre-polymerization and the obtained bio-based prepolymers were analyzed by determining the content of unreacted NCO groups, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, thermogravimetry, and rheological measurements. The research conducted facilitated the evaluation of the properties and processability of urethane prepolymers based on natural components. The results indicate that a significant impact on the processability has the origin the polyol ingredient as well as the NCO content. The thermal stability of all of the prepolymers is similar. A prepolymer based on a poly-ether polyol is characterized by a lower viscosity at a lower temperature than the prepolymer based on a polyester polyol. The viscosity value depends on the NCO content. Full article

Responsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polymer solution forms a hydrogel upon heating to physiological temperatures and undergoes slow degradation by hydrolytic cleavage of ester bonds. The disulfide functionality allows for immediate reductive cleavage of the redox-sensitive bond embedded within the polymer structure, affording the option of instantaneous hydrogel collapse. Poly(ethylene glycol)-b-poly(lactic acid)-S-S-poly(lactic acid)-b-poly(ethylene glycol) (PEG-PLA-SS-PLA-PEG) copolymer was synthesized by grafting PEG to PLA-SS-PLA via urethane linkages. The aqueous solution of the resultant copolymer was a free-flowing solution at ambient temperatures and formed a hydrogel above 32 °C. The immediate collapsibility of the hydrogel was displayed via reaction with NaBH₄ as a relatively strong reducing agent, yet stability was displayed even in glutathione solution, in which the polymer degraded slowly by hydrolytic degradation. The polymeric hydrogel is capable of either long-term or immediate degradation and thus represents an attractive candidate as a biocompatible material for the controlled release of drugs. Full article

The environmental and health hazards associated with petro-based chemicals have motivated the researchers to replace them partially or wholly with renewable resource-based polymers. Vegetable oils serve as an excellent alternative to this end as they are cost effective, eco-friendly, easily available and rich with functional groups amenable to chemical reactions. The aim of the research work is to prepare Canola oil [CANO] derived poly (ester–ether–amide–urethane) (CPEEUA) nanocomposite coating material using N,N-bis (2-hydroxyethyl) fatty amide [CFA] obtained from CANO, Lactic acid [LA], and reinforced with Fumed Silica [FS]. CPEEUA was obtained by esterification, etherification, and urethanation reactions and its structure was confirmed from FTIR and NMR spectral analyses. CPEEUA/FS coatings were found to be scratch resistant, flexible, well-adhered to mild steel panels, and hydrophobic with 2.0–2.5 kg scratch hardness, 150lb/inch impact resistance and >90° contact angle value. They exhibited good corrosion protection in 3.5 wt% NaCl solution as investigated by Potentiodynamic Polarization and Electrochemical Impedance tests. CPEEUA coatings are safe for usage up to 200 °C. Full article

A series of polycaprolactones (PCLs) with molecular weights of 950–10,100 g mol⁻¹ and Ð of 1.10–1.87 have been synthesized via one-pot, solvent-free ring-opening polymerization (ROP) of ε-caprolactone (CL) using a heterogeneous double metal cyanide (DMC) catalyst. Various initiators, such as polypropylene glycol, ethylene glycol, propylene glycol, glycerol, and sorbitol, are employed to tune the number of hydroxyl end groups and properties of the resultant PCLs. Kinetic studies indicate that the DMC-catalyzed ROP of CL proceeds via a similar mechanism with the coordination polymerization. Branched PCLs copolymers are also synthesized via the DMC-catalyzed copolymerization of CL with glycidol. The α,ω-hydroxyl functionalized PCLs were successfully used as telechelic polymers to produce thermoplastic poly(ester-ester) and poly(ester-urethane) elastomers with well-balanced stress and strain properties. Full article

Autograft (AG) is the gold standard for bone grafts, but limited quantities and patient morbidity are associated with its use. AG extenders have been proposed to minimize the volume of AG while maintaining the osteoinductive properties of the implant. In this study, poly(ester urethane) (PEUR) and poly(thioketal urethane) (PTKUR) AG extenders were implanted in a 20-mm rabbit radius defect model to evaluate new bone formation and graft remodeling. Outcomes including µCT and histomorphometry were measured at 12 weeks and compared to an AG (no polymer) control. AG control examples exhibited new bone formation, but inconsistent healing was observed. The implanted AG control was resorbed by 12 weeks, while AG extenders maintained implanted AG throughout the study. Bone growth from the defect interfaces was observed in both AG extenders, but residual polymer inhibited cellular infiltration and subsequent bone formation within the center of the implant. PEUR-AG extenders degraded more rapidly than PTKUR-AG extenders. These observations demonstrated that AG extenders supported new bone formation and that polymer composition did not have an effect on overall bone formation. Furthermore, the results indicated that early cellular infiltration is necessary for harnessing the osteoinductive capabilities of AG. Full article

In this work, we report the electrospinning and mechano-morphological characterizations of scaffolds based on blends of a novel poly(ester urethane urea) (PHH) and poly(dioxanone) (PDO). At the optimized electrospinning conditions, PHH, PDO and blend PHH/PDO in Hexafluroisopropanol (HFIP) solution yielded bead-free non-woven random nanofibers with high porosity and diameter in the range of hundreds of nanometers. The structural, morphological, and biomechanical properties were investigated using Differential Scanning Calorimetry, Scanning Electron Microscopy, Atomic Force Microscopy, and tensile tests. The blended scaffold showed an elastic modulus (~5 MPa) with a combination of the ultimate tensile strength (2 ± 0.5 MPa), and maximum elongation (150% ± 44%) in hydrated conditions, which are comparable to the materials currently being used for soft tissue applications such as skin, native arteries, and cardiac muscles applications. This demonstrates the feasibility of an electrospun PHH/PDO blend for cardiac patches or vascular graft applications that mimic the nanoscale structure and mechanical properties of native tissue. Full article