Biomedical Polyurethane Research Articles

A Novel Biomedical Polyurethane Material With Optimized Optical and Mechanical Properties Is Developed

Abstract This research aims to design and develop a novel polyurethane elastomer (PUE) material with potential for biomedical optical applications. The study investigates the influence of hard segment (HS) content on transparency and tensile strength to optimize optical and mechanical properties. A one-step polymerization method is employed to synthesize a series of PUEs based on polyester, poly (3-methyl-1,5-pentandioladipate) (PMPA), diisocyanate (4,4-methylene bis (phenyl isocyanate) (MDI)), and the chain extender 1,4 butanediol (BD). By varying the ratios of PMPA/BD/MDI, PUE samples with different HS concentrations are synthesized. Analytical techniques including infrared spectroscopy, refractometer, UV/visible spectrophotometer, and tensile tests confirm the chemical structure of the synthesized PMPAPUE materials and investigate refractive indices (n), transmission spectra, and Young's modulus (YM), respectively. Films (PUE-1, PUE-2, and PUE-3) prepared using solvent-casting techniques exhibit varying optical and mechanical properties. PUE-1, with low HS content, demonstrates excellent transparency, with n = 1.59 and 89.63% of total transmitted light, and possesses excellent elastic properties with a YM of 10.654 MPa and a high strain value of S = 303.7%, meeting lens material requirements, promising for biomedical optical applications. Conversely, PUE-2 and PUE-3, with high HS content, are translucent and stiffer materials exhibiting higher YM, suitable for polymer processing, and tissue engineering applications. The optimization of the material's properties was achieved by carefully tailoring the composition of HS and soft segments, raw material ratios, and optimizing reaction conditions.

A simple and efficient strategy for preparing anticoagulant coatings on biomedical polyurethane surfaces through a fluorinated urethane prepolymer

Developing an efficient yet uncomplicated method to achieve anticoagulant coatings on biomedical PU surfaces remains a challenge. In this research, we have proposed a very simple way to synthesize fluorinated urethane prepolymers (FPUs) that possess extended fluorocarbon side chains and terminal groups, innovatively using a new fluorinated chain extender and a fluorinated terminal capping agent. These FPUs have been utilized as additives to fabricate biomedical PU blends (BPUB). Incorporating a minimal quantity of FPUs, as little as 2.5 %, bestows BPUB with exceptional capabilities to resist protein and platelet adhesion, which can further prevent platelet activation, facilitated by the self-migrating nature of the fluorocarbon chains toward the film's upper surfaces, as substantiated by contact angle measurements and XPS. DSC and TG analysis indicate that the addition of FPUs marginally affects the thermal stability of the BPUB films, yet it reduces the glass transition temperature of the PUs. Remarkably, the BPUB films demonstrate enhanced degradation resistance to physiological solutions, exhibit excellent hemocompatibility, and maintain extremely low cytotoxicity levels. Thus, the FPUs present themselves as highly encouraging candidates for the development of anticoagulant coatings on biomedical polymers.

In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1H-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitro and in vivo settings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidis biofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.

An overview of polyurethane biomaterials and their use in drug delivery

Polyurethanes are a versatile and highly tunable class of materials that possess unique properties including high tensile strength, abrasion and fatigue resistance, and flexibility at low temperatures. The tunability of polyurethane properties has allowed this class of polymers to become ubiquitous in our daily lives in fields as diverse as apparel, appliances, construction, and the automotive industry. Additionally, polyurethanes with excellent biocompatibility and hemocompatibility can be synthesized, enabling their use as biomaterials in the medical field. The tunable nature of polyurethane biomaterials also makes them excellent candidates as drug delivery vehicles, which is the focus of this review. The fundamental idea we aim to highlight in this article is the structure-property-function relationships found in polyurethane systems. Specifically, the chemical structure of the polymer determines its macroscopic properties and dictates the functions for which it will perform well. By exploring the structure-property-function relationships for polyurethanes, we aim to elucidate the fundamental properties that can be tailored to achieve controlled drug release and empower researchers to design new polyurethane systems for future drug delivery applications.

In vitro evaluation of blood plasma coagulation responses to four medical-grade polyurethane polymers.

Segmented polyurethane (PU) block copolymers are widely used in implantable cardiovascular medical devices due to their good biocompatibility and excellent mechanical properties. More specifically, PU Biospan MS/0.4 was used in ventricular assist devices over the past decades. However, this product is being discontinued and it has become necessary to find an alternative PU biomaterial for application in cardiovascular devices. One important criterion for assessing cardiac biomaterials is blood compatibility. In this study, we characterized the surface properties of four medical-grade PU biomaterials: Biospan MS/0.4, BioSpan S, BioSpan 2F, and CarboSil 20 80A, including surface chemistry, topography, microphase separation structure and wettability, and then measured the blood plasma coagulation responses using bovine and human blood plasma. Results showed that BioSpan 2F contains high amounts of fluorine and has the lowest surface free energy while the other materials have surfaces with silicone present. An in vitro coagulation assay shows that these materials demonstrated improved blood coagulation responses compared to the polystyrene control and there were no significant differences in coagulation time among all PU biomaterials. The chromogenic assay showed all PU materials led to low FXII contact activation, and there were no significant differences in FXII contact activation, consistent with plasma coagulation responses.

Novel copper complexes-polyurethane composites that mimics anti-inflammatory response

Copper is a trace element of biological significance that can form complexes with several thiol containing compounds which can be used as filler in biomedical polyurethanes. In this work, segmented polyurethanes (SPUs) were synthesized with thiol containing compounds as chain extenders including d-penicillamine (DP), l-penicillamine (LP), l-cysteine (LC) and reduced glutathione (GR). Then, the synthesized polyurethane was filled with copper chelates based on the same chain extenders. Evidence of free thiol containing chain extender in polyurethane was not observed by FTIR and Raman but EDX provided evidence of sulfur in the unfilled polyurethane and copper and sulfur in their composite. DSC and DRX showed the semi-crystalline nature of the polyurethanes which provided good mechanical properties, especially to those prepared with DP. The Tg of the PCL determined by DMA shifted toward higher temperatures by the addition of copper complexes while TGA studies showed that the thermal degradation was slightly improved when LCCu and GRCu complex were added. Macrophage viability was observed in all composition studied after longer times of extraction (72 h) and dilutions (1:2 to 1:32) but remarkably high in those prepared with LCCu and GRCu. The anti-inflammatory response was proved in LC and GR copper complex filled polyurethanes as IL-4 and IL-10 increased with time while IL-1β and TNF-α were reduced.

Biomedical Polyurethanes for Anti-Cancer Drug Delivery Systems: A Brief, Comprehensive Review.

With the intensive development of polymeric biomaterials in recent years, research using drug delivery systems (DDSs) has become an essential strategy for cancer therapy. Various DDSs are expected to have more advantages in anti-neoplastic effects, including easy preparation, high pharmacology efficiency, low toxicity, tumor-targeting ability, and high drug-controlled release. Polyurethanes (PUs) are a very important kind of polymers widely used in medicine, pharmacy, and biomaterial engineering. Biodegradable and non-biodegradable PUs are a significant group of these biomaterials. PUs can be synthesized by adequately selecting building blocks (a polyol, a di- or multi-isocyanate, and a chain extender) with suitable physicochemical and biological properties for applications in anti-cancer DDSs technology. Currently, there are few comprehensive reports on a summary of polyurethane DDSs (PU-DDSs) applied for tumor therapy. This study reviewed state-of-the-art PUs designed for anti-cancer PU-DDSs. We studied successful applications and prospects for further development of effective methods for obtaining PUs as biomaterials for oncology.

Creative transformation of biomedical polyurethanes: from biostable tubing to biodegradable smart materials

Creative transformation of biomedical polyurethanes: from biostable tubing to biodegradable smart materials

Intelligent deformation of biomedical polyurethane

Intelligent deformation of biomedical polyurethane

Comparative Pull-Out Performances of Cephalomedullary Nail with Screw and Helical Blade According to Femur Bone Densities

This paper mainly examines the fixation performances of the cephalomedullary nail for the incidence of intertrochanteric (IT) fracture to guide the appropriate fixations with respect to the bone density in terms of a biomechanical perspective. It is substantially important to guide which types of fixation are applied during the operation since it tends to induce the backout or migration of the helical blade and screw according to weight and bone density. Biomedical polyurethane (PUR) foam blocks for simulating human bone are adopted with two grades of densities to simulate a normal person and an elderly person who has osteoporosis. Tensile and compression tests are conducted to analyze the tensile-compression anisotropy of PUR foams. Pull-out performances of screw and helical blades are evaluated from experimental perspectives, which are supported by comparison with the results of finite element method analysis. The clamping force of the screw is higher than the helical blade, about 177% in normal foam density and 198% in low foam density. After physical evaluation of the critical pull-out fixation force of screw and helical blade, we have suggested that stable fixation is guaranteed when the pull-out force is larger than projected force.

New cross-linkable poly[bis(octafluoropentoxy) phosphazene] biomaterials: Synthesis, surface characterization, bacterial adhesion, and plasma coagulation responses.

Biomaterial-associated microbial infection and thrombosis represent major issues to the success of long-term use of implantable blood-contacting medical devices. The development of new poly[bis(octafluoropentoxy) phosphazene (OFP) biomaterials provides new routes for combatting microbial infection and thrombosis. However, the limited mechanical properties of OFP to date render them unsuitable for application in medical devices and inhibit any attempts at subsequent surface topography modification. In this study, we synthesized cross-linkable OFPs (X-OFPs) with the different degrees of cross-linking in an effort to improve the mechanical properties. The results showed that the surface chemistry and surface topography of X-OFPs do not change significantly, but the surface mechanical stiffness increased after cross-linking. Atomic force microscopic phase images showed that the polymer phase separation structures changed due to cross-linking. Experiments with three bacterial strains: Staphylococcal epidermidis, Staphylococcal aureus, and Pseudomonas aeruginosa showed that bacterial adhesion was significantly decreased on the OFP and X-OFPs for both the pre-cross-linked and cross-linked as compared to polyurethane biomaterials. Furthermore, bacterial adhesions were lower on X-OFP surfaces than on pre-cross-linked materials, suggesting that mechanical stiffness is an important parameter influencing bacterial adhesion. Blood plasma coagulation responses revealed longer coagulation times for OFP and X-OFP materials than on polyurethanes, indicating that the new cross-linked OFPs are resistant to plasma coagulation compared to currently used polyurethane biomaterials.

Design, modeling and 3D printing of a personalized cervix tissue implant with protein release function

Cervical cancer induced by human papillomavirus (HPV) causes severe morbidity worldwide. Although cervical conization has been widely accepted as the most conventional surgery against cervical cancer, tissue defects and high recurrence rates have a significant negative impact on women’s mental and physical health. Herein we developed an implantable, personalized cervical implant with drug release function using 3D printing technology. The cervical implant was designed in cone-shape with hieratical porous structures according to the clinical data, 3D-printed using polyurethane by low-temperature deposition manufacturing (LDM), and finished by lyophilization. Anti-HPV protein was loaded into the porous structure under negative pressure afterwards. Elastic biomedical polyurethane and the porous structure ensured that these cervical implants were equipped with tailored mechanical properties comparable to physiological cervix tissue. Cytotoxicity and cytocompatibility tests indicated that these 3D-printed cervical implants supported cell adhesion and growth. More importantly, the cervical implants with regulated pores could help to quantitatively control the loading and release of anti-HPV protein to inhibit dissociative viruses near the cervix validly. As a result, the 3D-printed cervical implants in the present study showed considerable potential for use as functional tissue implants against HPV infection after cervical conization.

Effect of coagulation bath parameters on the morphology and absorption behavior of a skin–core filament based on biomedical polyurethane and native silk fibroin microparticles

This study investigates the effect of the constituents and temperature of a coagulation bath on the morphology and water absorption behavior of a skin–core filament, which has potential application in the field of controlled drug release, based on biomedical polyurethane (BPU) and native silk fibroin microparticles (NSFPs). BPU solution and BPU/NSFP blend solution were extruded from the cortex and core channel of a coaxial double injector into a coagulation bath with different constituents and at different temperatures to form filaments. Scanning electron microscopy analysis of the skin–core filament prepared by wet-spinning revealed that the addition of ethanol decreased the exchange speed between the solvent and non-solvent and led to the formation of micropores on the surface. Meanwhile, the interface between the cortex and core became pronounced and the water absorption capability of the filament decreased with increasing ethanol concentration in the coagulation bath. The high temperature of the coagulation bath also improved the exchange speed between the solvent and non-solvent; however, its effect on the morphology of the filament was weak. Thus, a skin–core filament with different morphologies and water absorption behaviors was fabricated by controlling the constituents and temperature of the coagulation bath during the wet-spinning process. This skin–core filament has potential applications in controlled drug release.

Blood coagulation response and bacterial adhesion to biomimetic polyurethane biomaterials prepared with surface texturing and nitric oxide release

A dual functional polyurethane (PU) film that mimics aspects of blood vessel inner surfaces by combining surface texturing and nitric oxide (NO) release was fabricated through a soft lithography two-stage replication process. The fabrication of submicron textures on the polymer surface was followed by solvent impregnation with the NO donor, S-nitroso-N-acetylpenicillamine (SNAP). An in vitro plasma coagulation assay showed that the biomimetic surface significantly increased the plasma coagulation time and also exhibited reduced platelet adhesion and activation, thereby reducing the risk of blood coagulation and thrombosis. A contact activation assay for coagulation factor XII (FXII) demonstrated that both NO release and surface texturing also reduced FXII contact activation, which contributes to the inhibition of plasma coagulation. The biomimetic surface was also evaluated for bacterial adhesion in plasma and results demonstrate that this combined strategy enables a synergistic effect to reduce bacterial adhesion of Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa microorganisms. The results strongly suggest that the biomimetic modification with surface texturing and NO release provides an effective approach to improve the biocompatibility of polymeric materials in combating thrombosis and microbial infection. Statement of significance(1) Developed a dual functional polyurethane (PU) film that mimics blood vessel inner surface by combining surface texturing and nitric oxide (NO) release for combatting biomaterial associated thrombosis and microbial infection. (2) Studied the blood coagulation response and bacterial adhesion to such biomimetic PU surfaces, and demonstrated that the combination of surface texturing and NO release synergistically reduced the platelet adhesion and bacterial adhesion in plasma, providing an effective approach to improve the biocompatibility of biomaterials used in blood-contacting medical devices. (3) The NO releasing surface significantly inhibits the plasma coagulation via the reduction of contact activation of FXII, indicating the multifunctional roles of NO in improving the biocompatibility of biomaterials in blood-contacting medical devices.

Mathematical modeling and experimental study of mechanical properties of chitosan based polyurethanes: Effect of diisocyanate nature by mixture design approach

This research work has been done to investigate the influence of the geometry of aliphatic diisocyanate (hexamethylene diisocyanate, HDI), cycloaliphatic diisocyanate (isophorone diisocyanate, IPDI) and aromatic diisocyanate (2,4-toluene diisocyanate, TDI) on the tensile strength and hardness of chitosan based polyurethane biomaterials. For this purpose, chitosan (CS) and polycaprolactone diol (PCL) based polyurethanes have been synthesized with above mentioned diisocyanates following statistical design (mixture design). Simplex mixture design was used for analysis and totally 10 experiments were generated by the software. Samples were tested based on the portions of mixture components. Fourier transform Infrared attenuated total reflection (FTIR-ATR) and nuclear magnetic resonance (NMR) spectroscopic techniques confirmed the synthesis of chitosan based polyurethanes. This biomaterial has been established as an innovative and promising strategy to improve the mechanical strength of chitosan-based polyurethanes.

Characteristics of Collagen-Rich Extracellular Matrix Hydrogels and Their Functionalization with Poly(ethylene glycol) Derivatives for Enhanced Biomedical Applications: A Review

The hydrogels of natural extracellular matrix (ECM) are excellent biomaterials with promising applications in the physiological manufacture of three-dimensional (3D) constructs that replicate native tissue-like architectures and function as cargo-delivery, 3D bioprinting, or injectable systems. ECM hydrogels retain the bioactivity to trigger key cellular processes in the tissue engineering and regenerative medicine (TERM) strategies. However, they lack suitable physicochemical properties, which restricts their applications in vivo. This demand that mechanical and degradation properties of the ECM hydrogels must be balanced against biological properties. By incorporating poly(ethylene glycol) (PEG) into mammalian type I collagen-rich ECM substrates, this task can be accomplished. This review is focused on the use of PEG derivatives, widely used in formulations of pharmaceutical products or in synthesis of biomedical polyurethanes, as a strategy to modulate both physical and biological properties of natural ECM hydrogels. The processing-property relationship in decellularized ECM hydrogels, as well as the main results when used in TERM, are discussed. A comparison of the characteristics of PEG-ECM hydrogels is provided in terms of the improvement of structure, mechanics, and degradation behavior. Finally, the benefits of producing PEG-ECM hydrogels according to in vitro and in vivo performance in different proofs-of-concept of emergent biomedical technologies are overviewed.

The effect of natural silk fibroin microparticles on the physical properties and drug release behavior of biomedical polyurethane filament

In this study, filaments comprising natural silk fibroin microparticles (NSFP) and biomedical polyurethane (BPU) were prepared via wet-spinning as a reusable-controlled drug-delivery system. The rheological properties of the spinning solution were studied to examine the effect of NSFP on the BPU/NSFP filament formation. The influences of NSFP content and spinning conditions on the morphology, molecular interactions, mechanical properties, and swelling performance of BPU/NSFP filaments were also investigated. The morphology and mechanical property studies showed that NSPF and BPU exhibit good compatibility. The capacity of the BPU/NSFP filaments as drug loading carriers and drug release behavior were studied by spectroscopy. The presence of NSFP in the drug controlled system increase the drug loading amount and enhance the drug release time. This paper presents a well-designed manufacturing method for preparing BPU/NSFP filaments with good controlled drug delivery.

Polyurethane tethering natural antibacterial substances for catheter applications

Antibacterial central venous catheters (CVC) have been in great demand in recent years. However, biomedical polyurethane (PU), the most used polymer for CVC extrusion, lacks antibacterial properties, surface coating after catheter extrusion or additives is generally required for fabricating antibacterial CVC. To develop antibacterial PU for CVC extrusion, a natural derived substance, benzoic acid, was thus grafted onto a PU with pendant alkynyl groups successfully through Cu(I)-catalyzed azide-alkyne cycloaddition click reaction in this research. The synthesized PU tethering benzoic acid (PUB) was fabricated into catheter which displays a suitable strength for CVC application. PUB tethering benzoic acid over 2 mmol/g has proved good antibacterial properties against Escherichia coli and Staphylococcus aureus based on a bacterial colony forming units test, and bone mesenchymal stem cells proliferation on PUB also demonstrate good cell compatibilities, suggesting PUB a promising polymer for CVC extrusion.

The effect of native silk fibroin powder on the physical properties and biocompatibility of biomedical polyurethane membrane.

Naturally derived fibers such as silk fibroin can potentially enhance the biocompatibility of currently used biomaterials. This study investigated the physical properties of native silk fibroin powder and its effect on the biocompatibility of biomedical polyurethane. Native silk fibroin powder with an average diameter of 3 µm was prepared on a purpose-built machine. A simple method of phase inversion was used to produce biomedical polyurethane/native silk fibroin powder hybrid membranes at different blend ratios by immersing a biomedical polyurethane/native silk fibroin powder solution in deionized water at room temperature. The physical properties of the membranes including morphology, hydrophilicity, roughness, porosity, and compressive modulus were characterized, and in vitro biocompatibility was evaluated by seeding the human umbilical vein endothelial cells on the top surface. Native silk fibroin powder had a concentration-dependent effect on the number and morphology of human umbilical vein endothelial cells growing on the membranes; cell number increased as native silk fibroin powder content in the biomedical polyurethane/native silk fibroin powder hybrid membrane was increased from 0% to 50%, and cell morphology changed from spindle-shaped to cobblestone-like as the native silk fibroin powder content was increased from 0% to 70%. The latter change was related to the physical characteristics of the membrane, including hydrophilicity, roughness, and mechanical properties. The in vivo biocompatibility of the native silk fibroin powder-modified biomedical polyurethane membrane was evaluated in a rat model; the histological analysis revealed no systemic toxicity. These results indicate that the biomedical polyurethane/native silk fibroin powder hybrid membrane has superior in vitro and in vivo biocompatibility relative to 100% biomedical polyurethane membranes and thus has potential applications in the fabrication of small-diameter vascular grafts and in tissue engineering.

Influence of Hard Segments on the Thermal, Phase-Separated Morphology, Mechanical, and Biological Properties of Polycarbonate Urethanes

In this study, we have fabricated a series of polycarbonate polyurethanes using a two-step bulk reaction by the melting pre-polymer solution-casting method in order to synthesize biomedical polyurethane elastomers with good mechanical behavior and biostability. The polyurethanes were prepared using dibutyltin dilaurate as the catalyst, poly(1,6-hexanediol)carbonate microdiols (PCDL) as the soft segment, and the chain extender 1,4-butanediol (BDO) and aliphatic 1,6-hexamethylene diisocyanate (HDI) as the hard segments. The chemical structures and physical properties of the obtained films were characterized by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimeter (DSC), and mechanical property tests. The surface properties and degrees of microphase separation were further analyzed by water droplet contact angle measurements (CA) and atomic force microscopy (AFM). The materials exhibited a moderate toxic effect on the tetrazolium (MTT) assay and good hemocompatibility through hemolytic tests, indicating a good biocompatibility of the fabricated membranes. The materials could be considered as potential and beneficial suitable materials for tissue engineering, especially in the fields of artificial blood-contacting implants or other biomedical applications.