Synthesis and degradation of nontoxic biodegradable waterborne polyurethanes elastomer with poly(ε-caprolactone) and poly(ethylene glycol) as soft segment

In this study, in order to obtain waterborne polyurethanes (WBPUs) with biocompatibility, biodegradability as well as good mechanical properties, a series of nontoxic cross-linked waterborne polyurethanes were designed and synthesized with isophorone diisocyanate (IPDI), poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), 1,4-butandiol (BDO) and l-lysine without any other organic agent involved in the whole synthetic process. The bulk structures and properties were characterized by DSC, IR and Instron, mainly focused on the effect of amount of PEG. Their corresponding biodegradability was examined with Lipase AK. The result showed that the prepared waterborne polyurethanes had very good tensile properties, allowing them to be well used as biomaterials. And the change of tensile properties with increasing of amount of PEG in the polymers could be assigned to the change of microphase separation, as indicated by DSC and IR data. A quite good biodegradability was achieved as judged from the change of tensile properties as a function of time. The current work demonstrated a new synthetic approach that can be more promising to prepare both nontoxic and biodegradable polyurethanes for soft tissue engineering applications or drug delivery.     

Characterization of Novel Biodegradable Segmented Polyurethanes Prepared from Amino-Acid Based Diisocyanate

Segmented polyurethanes (SPUs) which were expected to yield non-toxic degradation products were synthesized from lysine-based diisocyanate (LDI), 1,3-propanediol (PDO), and polycaprolactone diol (PCL). SPUs were synthesized via a standard two-step prepolymer method. The hard segment fraction was changed in order to tune the mechanical properties and the degradability. The aggregation structures of the SPUs were characterized by infrared spectroscopy and differential scanning calorimetry (DSC), temperature dependence of dynamic viscoelasticity, and small-angle X-ray scattering (SAXS). DSC and dynamic viscoelastic measurements revealed that the glass transition temperature (T_g) of the soft segment increased with an increase in the hard segment fraction. SAXS of SPUs revealed the aggregation states of hard and soft segments. Furthermore, the degradation of SPUs was investigated by exposing the polymers to a buffer solution at 310 K (pH=7.6). The degradation rate of SPUs increased with an increase in the soft segment fraction. This is because the soft segment has the hydrolyzable ester linkages and the ester linkages are susceptible to hydrolysis compared with the urethane linkages. Finally, an electrospray deposition method was used to fabricate biodegradable SPU micro-fibers. FE-SEM images showed that higher concentration of solution favored the formation of uniform biodegradable micro-fibers without beads-like structure.     

Effect of Chain Extender on Hydrogen Bond and Microphase Structure of Biodegradable Thermoplastic Polyurethanes

Thermomechanical properties of polyurethanes (PUs) strongly depend on the molecular interactions and microphase structure.In this work,two chain extenders with different ratios,flexile 1,4-butanediol (BDO) and branched trimethylolpropane mono allyl ether (TMPAE),are used to tune the molecular interactions and microphase structures of a series of biodegradable thermoplastic polyurethanes (TPUs).In TPUs,the biodegradable polycaprolactone (PCL,Mn of 2000) is used as soft segment while 1,6-diisocyanatohexane (HDI) and chain extenders are used as hard segment.Fourier transform infrared spectroscopy (FTIR),proton nuclear magnetic resonance spectroscppy (1H-NMR),gel permeation chromatography (GPC),differential scanning calorimetry (DSC),dynamic mechanical analysis (DMA) and mechanical tests were performed to characterize the bulk structure and properties of TPUs.Compared with BDO,the steric bulk of TMPAE is larger.The increment of TMPAE can help to increase the hydrogen bond content,microphase separation,and the elastic modulus ratio (R),which would strongly affect the thermomechanical property of the TPUs.The results of this work verify the importance of the structure of chain extender on the properties of TPUs.It provides valuable information for further understanding the structure-property relationships of these polyurethanes.     

Injectable Hyaluronic Acid/Poly(γ-glutamic acid) Hydrogel with Step-by-step Tunable Properties for Soft Tissue Engineering

Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering. However, their crosslinking degree is difficult to be controlled after being injected into body. As we all know, the crosslinking degree strongly influences the physicochemical properties of hydrogels. Therefore, developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering. Herein, we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization. The developed hyaluronic acid/poly(γ-glutamic acid)(HA/γ-PGA) hydrogels exhibit step-bystep tunable swelling behavior, enzymatic degradation behavior and mechanical properties. Mechanical performance tests show that the storage moduli of HA/γ-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal, which have a good match with soft tissue. In addition, NIH 3 T3 cells encapsulated in HA/γ-PGA hydrogel exhibit a high cell viability, indicating a good cytocompatibility of HA/γ-PGA hydrogel.Therefore, the developed HA/γ-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.     

Phase morphology of hydrolysable polyurethanes derived from aqueous dispersions

Biodegradable polyurethanes are an interesting alternative to many applications that involve plastics since they can minimize environmental problems caused by the low rates of natural degradation of synthetic polymers. In addition, since waterborne polyurethanes are based on aqueous dispersions, they restrict the use of organic solvents during processing and application of the polymer, thus contributing furthermore to reduce environmental damage. In this work, aqueous anionic polyurethane dispersions (PUD) with tailorable susceptibility for hydrolysis were synthesized by progressively replacing polypropylene glycol (PPG) with a biodegradable polycaprolactone diol (PCL) as soft segments. The hard segments were formed by extending isophorone diisocyanate (IPDI) with hydrazine (HZ). Dimethylol propionic acid (DMPA) was used as ionic center and triethyl amine (TEA) as neutralizer. The degree of phase separation was evaluated mainly by infrared spectroscopy (FTIR) and small angle X-ray scattering (SAXS). The results indicated that phase separation between hard and soft segments of poly(ester-urethane) is more significant than that of poly(ether-urethane). Data obtained from SAXS experiments indicated that phase separation within soft domains can also be present in samples containing both polyester and polyether soft segments. Hydrolytic degradation of the polymers in buffer solution of pH 7.4 and alkaline solution was performed as an initial test. The results showed that the fraction of polyester soft segments in the polyurethanes can be used to tailor the susceptibility of the materials to hydrolytic attack. Polyurethanes having higher contents of polyester were more promptly hydrolytically degraded than polyurethanes containing only polyether segments.     

A structural reconsideration: Linear aliphatic or alicyclic hard segments for biodegradable thermoplastic polyurethanes?

Thermoplastic polyurethane elastomers (TPUs) with a biodegradable chain extender and different nonaromatic diisocyanate hard segments were synthesized and tested concerning their thermal, mechanical, and degradation properties and for their processability regarding electrospinning. The design of the TPUs was based on the structural modification of the hard segment using linear aliphatic hexamethylene diisocyanate (HMDI), more rigid alicyclic 4,4′-methylene bis(cyclohexylisocyanate) (H12MDI), 1,3-bis(isocyanatomethyl)cyclohexane (BIMC), or isophorone diisocyanate (IPDI). The soft segment consisted of poly(tetrahydrofuran). Bis(2-hydroxyethyl) terephthalate (BET) was used as chain extender with cleavable ester bonds. Some of the polyurethanes based on alicyclic diisocyanate showed better mechanical performance than the less rigid HMDI-based TPU. The TPU in vitro degradability was tested for 25 days at elevated temperatures in PBS buffer and indicated a bulk erosion process. Electrospinning experiments were conducted and promising results with respect to further applicability of these materials in vascular tissue engineering were obtained. © 2018 The Authors Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2214–2224     

Photo-crosslinking copolymers based polyanhydride and 1G polyamidoamine-methacrylamide as bone tissue engineering: Synthesis, characterization, and in vitro degradation

In the past decade, Biodegradable materials that are capable of in situ formation have attracted increased attention for use in restorative orthopedic devices. In this communication, the surface erosion biodegradable polymers derived from 1.0G-polyamidoamine-double bond (PAMAM-DB) and methacrylated sebacic anhydrides (MSA) were evaluated over 2 months period under physiological conditions. Rectangular shaped samples were prepared by crosslinking the components using both chemical and photo initiators and exposure to UV light. The effects of PAMAM-DB: MSA ratio on local pH, water uptake, mass loss, and mechanical properties were explored. Polymers were characterized by ¹H NMR, ¹³C NMR, FT-IR, compressive strength testing and SEM. It is found that copolymer with 50-60% PAMAM-DB (mass fraction) show more excellent mechanical properties compared with other formulations. Copolymers degraded mainly by surface erosion but the bulk erosion pattern also appeared at the initial time of degradation for formulation 30% and 40%. The material was expected to be useful for drug controlled delivery, tissue engineering scaffold and other biomedical applications.     

Ultraviolet‐induced crosslinking of poly(butylene succinate) and its thermal property,dynamic mechanical property,and biodegradability

Crosslinking is an effective way to improve polymer properties. This paper focuses on ultraviolet‐induced crosslinking of poly(butylene succinate) (PBS) in the presence of a photoinitiator and a crosslinking agent at ambient temperature. The effects of the concentration of photoinitiator, the crosslinking agent content, and the irradiation time on the crosslink behavior were investigated. To obtain an appropriate gel fraction in different irradiation times, 3.0 wt% of photoinitiator and 10.0 wt% of crosslinking agent were proved to be the optimum choice. Furthermore, properties such as thermal properties, dynamic mechanical property, and enzymatic degradation of PBS before and after crosslinking were examined. Differential scanning calorimetry (DSC) analysis revealed that glass transition temperature (T_g) increased with increase in gel fraction, while melting temperature (T_m) and the degree of crystallinity decreased. This may be caused by the reduced molecular chain mobility and inhibited molecular motion for crystallization in crosslinked samples. The crosslinked polymer also showed improved thermal stability and dynamic mechanical property. In addition, the introduction of crosslinking retarded the enzymatic degradation rate of PBS, but it was still biodegradable. The improved properties of crosslinked PBS will extend the application of PBS. Copyright © 2009 John Wiley & Sons, Ltd.     

Novel 3D printed shape-memory PLLA-TMC/GA-TMC scaffolds for bone tissue engineering with the improved mechanical properties and degradability

The biodegradable substitution materials for bone tissue engineering have been a research hotspot. As is known to all, the biodegradability, biocompatibility, mechanical properties and plasticity of the substitution materials are the important indicators for the application of implantation materials. In this article, we reported a novel binary substitution material by blending the poly(lactic-acid)-co-(trimethylene-carbonate) and poly(glycolic-acid)-co-(trimethylene-carbonate), which are both biodegradable polymers with the same segment of flexible trimethylene-carbonate in order to accelerate the degradation rate of poly(lactic-acid)-co-(trimethylene carbonate) substrate and improve its mechanical properties. Besides, we further fabricate the porous poly(lactic-acid)-co-(trimethylene-carbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate) scaffolds with uniform microstructure by the 3D extrusion printing technology in a mild printing condition. The physicochemical properties of the poly(lactic-acid)-co-(trimethylene-carbonate)/poly(glycolic-acid)-co-(trimethylene-carbonate) and the 3D printing scaffolds were investigated by universal tensile dynamometer, fourier transform infrared reflection (FTIR), scanning electron microscope (SEM) and differential scanning calorimeter (DSC). Meanwhile, the degradability of the PLLA-TMC/GA-TMC was performed in vitro degradation assays. Compared with PLLA-TMC group, PLLA-TMC/GA-TMC groups maintained the decreasing T_g, higher degradation rate and initial mechanical performance. Furthermore, the PLLA-TMC/GA-TMC 3D printing scaffolds provided shape-memory ability at 37 ℃. In summary, the PLLA-TMC/GA-TMC can be regarded as an alternative substitution material for bone tissue engineering.     

Kinetics of the crosslinking reaction of nonionic polyol dispersion from terpene-maleic ester-type epoxy resin

The bulk crosslinking reaction kinetics of a novel two-component waterborne polyurethanes (2K-WPUs) composed of a bio-resin-based polyol dispersion and a hydrophilically modified hexamethylene diisocyanate tripolymer are investigated by freeze–drying and differential scanning calorimetry (DSC) technique at different heating rates. The data fit for the above two components is implemented with the nth-order kinetics equation and Málek’s mechanism function method, respectively. The kinetic parameters of crosslinking reaction are determined by the kinetic analysis of the data obtained from the thermal treatment, and then the kinetic model is built. The results indicate that the nth-order model deduced from Kissinger and Crane equation has great distinction with the experimental data, while the Málek analytic mechanism shows that the crosslinking process of the crosslinking reaction follows an autocatalytic reaction. The two-parameter (m and n) autocatalytic model (S–B model) can well describe the crosslinking reaction process of the studied 2K-WPU. The DSC curves derived from the experimental data show a good agreement with the theoretical calculation under 5–20 °C min^?1 heating rate. The results provide theoretical basis for the choice of the manufacturing process and the optimization of processing window.     

Effect of phase separation on the crystallization of soft segments of green waterborne polyurethanes

Effect of phase separation on the crystallization of soft segments of green waterborne polyurethanes (WPUs) was discussed in this paper. Phase separation was studied through dynamic mechanical analysis and energy dispersive spectrometer. Energy dispersive spectrometer was employed originally for the study of phase separation of polyurethanes in our study. Crystallization of soft segments of green WPUs was characterized by differential scanning calorimetry, X-ray diffraction and polarizing optical microscope. Characterization results indicated that phase separation hindered the crystallization of soft segments of green WPUs; higher phase separation degree gave rise to lower crystallization capacity, lower crystallinity and smaller crystals of soft segments.     

Synthesis and characterization of novel biodegradable folate conjugated polyurethanes

In order to obtain targeting polyurethane micelle drug carriers, a series of biodegradable folate conjugated polyurethanes (FPUs) were synthesized using poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) as soft segments, L-lysine ethyl ester diisocyanate (LDI) and 1,3-propanediol (PDO) as hard segments, and folic acid-ethylenediamine conjugate (FA-EDA) as an end-capping reagent. The resultant FPUs were fully characterized by (1)H NMR, Fourier-transform infrared (FTIR) spectroscopy, ultraviolet spectrophotometry (UV), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). These polymers can self-assemble into micelles in aqueous solutions confirmed by dynamic light scattering (DLS), pyrene fluorescence probe techniques, and transmission electron microscopy (TEM). The results indicated that the bulk structures and micellar properties of the prepared polyurethanes could be controlled by varying the PEG content in the soft segments. The present work provides a facile approach to prepare amphiphilic multiblock copolymers with tumor targeting moiety, which is a good candidate as biodegradable carriers for active intracellular drug delivery.     

生物可降解医用聚氨酯及其应用

生物可降解医用聚氨酯由于其优良的生物相容性、降解性、功能化修饰和力学性能可调控等优点,逐渐引起研究者的关注,尤其在药物传递和组织工程支架等方面可望具有广阔的应用前景。结合本课题组开展的工作,本文综述了生物可降解医用聚氨酯材料在结构、功能化设计及医学应用上的研究进展,并展望了其在医学材料中的发展前景。     

The effect of thiolation on the mechanical and protein adsorption properties of polyurethanes

Segmented polyurethanes are important polymers for a number of industrial and technological applications. The purpose of this work was to synthesize polybutadiene-based polyurethanes and subsequently graft carboxylate and sulfonate side chains via thiol-ene reaction. Spectroscopic investigations showed that grafting yielded good conversion for the vinyl unsaturation of the polybutadiene soft segment. DSC and tensile testing revealed that grafted polyurethanes had a better segmental compatibility and superior mechanical properties than the control polyurethane without grafting. The carboxylic side chains of the soft segment were responsible for the observed improved mechanical properties. Initial protein adsorption tests on these polymers were found to be higher than the control surface. The polyurethanes of the current study could be used for biomedical applications where protein attachment to the surface is needed for specific cell adhesion and tissue repair.     

Mechanical and dielectric properties of segmented polyurethane elastomers containing chemical crosslinks in the hard segment

Mechanical and dielectric properties of two series of segmented polyurethanes having soft segment concentration of 50 and 70% and a varying degree of crosslinking through the hard segment were studied. The degree of crosslinking in each series was varied by varying the butane diol/trimethylol propane ratio in the chain extender mixture. Tensile strength, elongation at break decrease, but elastic recovery increases monotonically with increasing crosslinking. The plateau modulus in the dynamic mechanical test decreases and then increases with increasing TMP content. Crosslinking causes broadening of the soft segment glass transition as seen by permittivity and loss factor measurements. It also affects high temperature behavior (above the glass transition of the hard segment); it lowers permittivity, loss factor, and ionic conductivity. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36 : 237–251, 1998     

Effect of starch content on the biodegradation of polycaprolactone/starch composite for fabricating in situ pore-forming scaffolds

Bone tissue engineering is an efficient approach to regenerating bone-related defects. The optimal scaffold used for bone tissue engineering must possess adequate porosity and suitable mechanical properties. This work described the development of a biodegradable polymeric composite based on polycaprolactone (PCL) and starch that can form a porous structure in situ. The scaffold exhibited the required mechanical properties at the initial stage of implantation by controlling in situ degradation and subsequent pore formation. PCL/starch (SPCL) scaffolds with 100/0, 70/30, and 50/50 ratios were developed. Degradation studies were performed in phosphate buffer saline (PBS) containing α-amylase or lipase at 37 °C for 4 weeks. Fourier-transform infrared spectroscopy was used to analyze chemical bonds and their changes after degradation. Differential scanning calorimetry was applied to determine the crystallinity and recrystallization of samples before and after degradation. Mass loss and starch release were observed during degradation, and the porosity of samples was measured by the ethanol replacement method. Morphology was further determined using scanning electron microscopy. Finally, variations in compressive strength and modulus during degradation and pore formation were also measured. The porosity of samples reached 45% after 1 month of degradation, and mechanical properties were still appropriate for human bone tissue. Reduction in mechanical property after mass loss, starch release and pore formation was controlled by the hydrogen bonding and recrystallization effect of PCL after degradation. Results suggested that SPCL composite had potential to form porous scaffold with adequate mechanical properties in situ and is promising for bone tissue engineering applications.     

Biodegradation of polyurethanes and nanocomposites to non-cytotoxic degradation products

Polyurethanes with controllable biodegradable properties have been considered for biomedical applications. However, the potential toxicity of their biodegraded by-products is still a concern. In this study, biodegradable polyurethanes based on poly(?-caprolactone) (PCL) and/or poly(ethylene glycol) as soft segments and biodegradable polyurethanes containing montmorillonite nanoparticles were synthesized and were subjected to in vitro biodegradation for 4 months. The post-degraded polyurethanes and nanocomposites were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and small angle X-ray scattering (SAXS). The toxicity of the biodegradation by-products was evaluated by measuring their effect on the viability of retinal cells. FTIR results indicated that hard segments of the biomaterials were preserved during biodegradation, and suggested that the ester bonds of the PCL incorporated into the soft segments were hydrolytic broken. XRD data indicated also that the soft segments crystallized as a result of the hydrolysis of PCL ester bonds and re-organization of the amorphous phase during annealing at 37 °C. As the biodegradation of the biomaterials induced the formation of soft segment lamella crystals, a complex nanostructure was formed, resulting in the enhancement of the small angle X-ray scattering. The by-products were non-cytotoxic to the retinal cells. These results suggest that the hydrolytic unstable polyurethanes and nanocomposites can be possible candidates for ophthalmological applications.     

脂肪族水性聚氨酯的动态力学行为研究

合成了一系列脂肪族水性聚氨酯 .考察了软段的组成、软段分子量及DMPA用量对产物动态力学性能的影响作用 .实验结果表明 ,软段的化学结构对水性聚氨酯的相态结构影响很大 .聚醚型水性聚氨酯具有较低的软段玻璃化转变温度 (Tgs) .聚醚型产物的微相分离程度高于聚酯型产物 .当采用聚酯和聚醚二元醇为混合软段时 ,Tgs随软段中聚醚含量的提高而逐渐降低 .提高DMPA用量 ,软段玻璃化转变温度Tgs移向低温区 ,硬段玻璃化转变温度Tgh移向高温区 ,说明体系的微相分离程度加大 .当软段分子量较低时 ,产物为半相容结构 ,只有一个主转变峰 ,软段的玻璃化转变以肩峰的形式出现 ;当软段分子量较高时 ,产物的微相分离程度较高 ,可以分别观察到软段及硬段的玻璃化转变 .总之 ,通过改变软段的种类、组成和分子量以及DMPA用量 ,可以大幅度地改变水性聚氨酯的形态结构 .     

Thermal properties of poly(urethane-ester-siloxane)s based on hyperbranched polyester

Novel polyurethanes (PUs) were synthesized using hydroxy-terminated hyperbranched polyester (BH-20) and 4,4′-methylenediphenyl diisocyanate (MDI) as hard segments and hydroxy-terminated ethylene oxide-poly(dimethylsiloxane)-ethylene oxide triblock copolymer (PDMS-EO) as soft segment, with soft segment content ranging from 30 to 60 wt %. The PUs were synthesized by two-step solution polymerization method. The influence of the soft segment content on the structure, swelling behavior and thermal properties of PUs was investigated. According to the results obtained by swelling measurements, the increase of the hard segment content resulted in the increase of the crosslinking density of synthesized samples. DSC results showed that the glass transition temperatures increase from 36 to 65°C with increasing hard segment content. It was demonstrated using thermogravimetric analysis (TGA) that thermal stability of investigated PUs increases with increase of the soft PDMS-EO content. This was concluded from the temperatures corresponding to the 10 wt % loss, which represents the beginning of thermal degradation of samples.     

Biodegradable elastomers for tissue engineering and cell-biomaterial interactions

Synthetic biomaterials serve as a cornerstone in the development of clinically focused regenerative medicine therapies that aim to reduce suffering and prolong life. Recent improvements in biodegradable elastomeric materials utilize natural extracellular matrix proteins as inspiration to yield a new class of materials with superior degradation kinetics, desirable biocompatibility profiles, and mechanical properties that closely match those of soft tissues. This review describes several classes of synthetic biodegradable elastomers and associated fabrication techniques that are relevant to scaffold development. The application of these materials to select tissue engineering models is also discussed.