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Preparation of POSS-PCLU polyurethane by reacting polycaprolactone diol and trans -cyclohexanechloroydrinisobutyl-POSS with two diisocyanates and chain extending the resulting polyurethane prepolymer with ethylenediamine.
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The field of tissue engineering is rapidly evolving, generating numerous biodegradable materials suited as regeneration platforms. Material sterility is of fundamental importance for clinical translation, yet, few studies have systematically researched the effects of different sterilization methods on biodegradable materials. Here, we exposed a nov...
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... flask equipped with a mechanical stirrer and nitrogen inlet. The mixture was heated to 135 ° C to dissolve the POSS nanocage and then cooled to 60 ° C. To this, dicyclohexylmethane diisocyanate (Desmodur W, Bayer) was added and reacted under nitrogen at 70 ° C for 90 min to form a pre- polymer. Then, N,N-dimethylacetamide (DMAC) was added and the mixture cooled to 40 ° C. A mixture of ethylenediamine and diethylamine in DMAC was added to allow chain extension of the pre-polymer. 1-Butanol in DMAC was added to the mixture to form an 18 % POSS-PCLU solution. All chemicals and reagents were purchased from Sigma Aldrich Ltd. (Gillingham, UK). Figure 1 schematically represents the reaction steps involved in the synthesis of a polyurethane ...
Citations
... Addition of PEG provided more hydrophilicity, increased cellular proliferation rate leading to faster regeneration of defected knee cartilage (Fuse et al., 2015). Polyurethane (PU) films and mats are made from PCL-diol for skin tissue engineering application (Yildirimer and Seifalian, 2015). PCL mats modified with biological molecules like collagen, fibronectin showed enhanced cell attachment and differentiation (Campagnolo et al., 2016). ...
With the development of biomedical research over the last few decades, biodegradable polymeric biomaterials have gained tremendous attraction in biomedical field due to its ease of synthesis with tunable properties like biodegradation, mechanical properties, stimuli responsive etc. Both natural polymers such as cellulose, chitosan, alginate, collagen, gelatin etc., and synthetic polymers including polycaprolactone (PCL), polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG) etc., have been extensively studied for biomedical applications like drug delivery system, gene delivery vector, tissue engineering, biosensors etc. Polymers have been used in biomedical applications in different forms like hydrogel, nanoparticles, composites or nanocomposites, porous sponge, 3D porous scaffold etc. Despite the several advantages of polymeric materials, still some modifications of existing natural biopolymers or some strategies to synthesis new biopolymers are adopted to improve different properties like solubility, degradation rate, toxicity, immunogenicity, stability etc. Here, we will discuss about the advancement of different biopolymers with respect to their synthesis procedures, degradation properties, toxicity, stability as well as their application in different biomedical fields elaborately.
... Ethanol treatment (70% v/v) has been previously shown to modify surface properties of polyurethanes but this sterilisation approach (on the POSS-PCLU polymer) did not significantly influence the mechanical properties or the cellular interactions 134,189 . For this study polymer samples were sterilised by washing in TWEEN® 20 for one minute (to remove endotoxins) followed by 70% ethanol, with phosphate buffered saline (PBS) washes between. ...
... Hydrolysis of PCL with intermediate steps and degradation products.1.7.4 POSSPolyhedral oligomeric silsesquioxane (POSS) was developed for biomedical applications in the 1960s and is now used in a wide variety of applications131 .POSS can be used to create nanocomposite materials with properties that allow even greater control of the material physicochemical properties that enables tailored materials for specific applications 132, 133 .1.7.5 POSS PCLUPOSS PCLU is a propriety polymer consisting of polyhedral oligomeric silsesquioxane (POSS) nanoparticles suspended in poly(e-caprolactone urea) (PCLU) and was developed as a degradable evolution of a similar POSS containing polyurethane POSS PCU (UCL-Nano™)134 . Its properties and applications have been extensively investigated as part of previous work within this laboratory105,[135][136][137] .POSS PCU has been used for tear duct replacement 138 while vascular grafts and synthetic scaffolds for tissue regeneration have been investigated in vitro137,139,140 . ...
Oesophageal leaks and perforations carry mortality and morbidity. Management options include surgery, stents, drains, and negative pressure therapy; all current treatment options, however, have significant associated morbidity. Here we investigate an alternative approach using a temporary polymer patch to adhere to and seal the oesophageal defect whilst supporting healing and function without damaging local tissue. This approach could offer a timely, cost effective and minimally invasive approach, especially for environments where specialised and complex surgery may not be available such as resource limited military and humanitarian healthcare settings. To quantitatively compare perforation management options (including the novel patch) a novel ex vivo model of oesophageal perforation repair was developed. The patch had a degradable poly(ε-caprolactone urea) urethane backbone with a polyhedral oligomeric silsesquioxane (POSS PCLU) component. The study successfully developed an ex vivo porcine oesophagus bench top model for testing the strength of oesophageal repair techniques. The model allowed a maximum pressure of 100kPa and was capable of quantitatively assessing perforation repair approaches. A major consideration in the patch approach to perforation repair is the adhesion of the patch to the oesophagus. The study demonstrates that the surface chemistry of the patch can be modified to improve adhesion and increase attachment strength. Here we found that both modifications of the tissue adhesion site in vivo (by removal of the outer epithelial layer of the oesophagus) and by modifying the surface chemistry of the patch (by plasma treatment) it was possible to enhance fibrin patch adhesion to the oesophagus. The optimisation of the patch surface chemistry and host tissue site for fibrin-based adhesion could have an impact in the medical use of polymer patches throughout the body.
... Our group have developed and patented two families of nanocomposite polymers for the development of organs and tissues [7][8][9]. The nonbiodegradable polymer incorporates POSS nanoparticles into polycarbonate-based ureaurethane (POSS-PCU, UCL-Nano). ...
... Adipose derived stem cells (ADSCs) were shown to adhere to the POSS-PCL scaffolds following ethanol and bleach sterilisation [8]. Lastly, a study comparing the effects of autoclave, microwave, antibiotics, and 70% ethanol sterilisation on POSS-PCL scaffolds found ethanol to be a suitable sterilisation technique with maintained fibroblast attachment [9]. The aim of this study was to compare all available sterilisation techniques for POSS-PCU and POSS-PCL in a single study including a new method using argon plasma sterilisation, building on previous studies, to understand the optimal sterilisation technique for nanocomposite scaffolds. ...
An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices.
... For example, PCL-diol could be used to prepare polyurethanes. This kind of polymer films and mats were produced by forming a bioabsorbable poly(ε-caprolactone urea) urethane backbone integrating-polyhedral oligomeric silsesquioxane nanoparticles for skin tissue engineering [97]. Films (300 μm thickness) and mats (800 μm thickness) were prepared by solvent evaporation and porogen leaching techniques, respectively, and effect of sterilization techniques as autoclave, microwave, antibiotic solution and 70% ethanol were studied where ethanol sterilization provided more clearance, less damage to structure and higher cell viability. ...
Biodegradable polymers have met withan increasing demand in medical usage over the last decades. One of such polymers is poly(ε-caprolactone) (PCL), whichis a polyester that has been widely used in tissue engineering field for its availability, relatively inexpensive price and suitability for modification. Its chemical and biological properties, physicochemical state, degradability and mechanical strengthcan be adjusted, and therefore,it can be usedunderharsh mechanical, physical and chemical conditions without significant loss of its properties. Degradation time of PCL is quite long, thus it is used mainly in the replacement of hard tissues inthe body where healing also takes an extended period of time. It is also used at load-bearing tissues of the body by enhancing its stiffness. However, due to its tailorability, use of PCL is not restricted to one type of tissueand it can be extended to engineering of soft tissues by decreasing its molecular weight and degradation time. This review outlines the basic properties of PCL, its composites, blends and copolymers. Wereport on various techniquesforthe productionof different forms, and provide examples ofmedical applications such as tissue engineering and drug delivery systemscovering the studies performed in the last decades.
... This result was contradictory to a previous study showing no changes to POSS-PCL macrostructure after two 15 min intervals of 70% ethanol exposure. 21 We believe that this may be due to the fact that we exposed POSS-PCL scaffolds to a continuous 30-min treatment of 70% ethanol. GPC results showed that ethanol sterilisation was associated with a 21% decrease in the Mn of POSS-PCL. ...
Objective:
Selection of the appropriate sterilisation method for biodegradable materials has been a challenging task. Many conventional sterilisation methods are not suitable for the next generation of biomaterials, mainly due to their complex composition, based on nanomaterials, often incorporating bioactive moieties. In this study, we investigate sterilisation efficacy of slow chlorine releasing compound sodium dichloroisocyanurate dihydrate (SDIC) for polyhedral oligomeric silsesquioxane (POSS)-poly(caprolactone urea-urethane) (PCL) scaffolds in comparison with conventional sterilisation methods.
Methods:
POSS-PCL scaffolds were subjected to 70% ethanol, UV, and SDIC sterilisation methods. Samples were immersed in tryptone soya broth (TSB) and thioglycollate medium (THY) and after seven days visually inspected for signs of microbial growth. Bulk and surface properties and molecular weight distribution profiles of the scaffolds after sterilization were investigated using FTIR analysis, surface hydrophilicity, scanning electron microscopy analysis, tensile strength testing, and gel-permeation chromatography (GPC). Adipose-derived stem cells (ADSC) were seeded on the scaffolds and AlamarBlue® viability assay was performed to investigate cell metabolic activity. Confocal imaging of rhodamine phalloidin and Dapi stained ADSC on scaffolds was used to demonstrate cell morphology.
Results:
GPC results showed that autoclaving led to a significant decrease in the molecular weight of POSS-PCL, whereas ethanol caused visible deformation of the polymer 3D structure and UV radiation did not effectively sterilise the scaffolds. AlamarBlue® analysis showed metabolic activity close to that of tissue culture plastic for ethanol and SDIC.
Conclusion:
SDIC sterilisation can be safely applied to biodegradable scaffolds unsuitable for the more common sterilisation methods.
... These findings are in line with previous reports demonstrating that particularly nanorough surfaces impair fundamental processes, which are crucially involved in vascularization and incorporation of biomaterials, such as cell growth, migration, and adhesion. 34,35 For instance, Pennisi et al. 34 found that in response to nanotopography fibroblasts spread less and exhibit an elongated morphology, displaying characteristics of actin cytoskeleton impairment and reduced formation of focal adhesion complexes. Moreover, they detected a lower expression of migration-related genes. ...
Porous polyethylene (Medpor®) is commonly used in craniofacial reconstructive surgery. Rapid vascularization and tissue incorporation are crucial for the prevention of migration, extrusion, and infection of the biomaterial. Therefore, we analyzed whether surface modification by plasma etching may improve the early tissue response to Medpor®. Medpor® samples were treated in a plasma chamber at low (20 W; LE-PE) and high energy levels (40 W; HE-PE). The samples and non-treated controls were implanted into mouse dorsal skinfold chambers to analyze angiogenesis, inflammation, and granulation tissue formation over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. Scanning electron microscopy (SEM) analyses revealed that elevating energy levels of plasma etching progressively increase the oxygen surface content and surface roughness of Medpor®. This did not affect the leukocytic response to the implants. However, LE-PE and HE-PE samples exhibited an impaired vascularization. This was associated with a reduced formation of a collagen-rich granulation tissue at the implantation site. Additional in vitro experiments showed a reduced cell attachment on plasma-etched Medpor®. Thus, plasma etching may not be recommended to improve the clinical outcome of reconstructive interventions using Medpor®. However, it may be beneficial for temporarily implanted polyethylene-based biomedical devices for which tissue incorporation is undesirable. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.
... Incorporation of this nanoparticle into poly-caprolactone (PCL) resulted in the synthesis of POSS-incorporated poly (caprolactone) urea/ urethane (POSS-PCL) nanocomposite polymer with considerably enhanced physiochemical properties including increased in tensile strength and surface roughness compared to conventional PCL (Chawla et al., 2014). Scaffold made of this nanocomposite are currently under investigation for nerve and skin (Yildirimer and Seifalian, 2015) tissue regeneration and implants needed for paediatric cases. ...
There is a high clinical demand for new smart biomaterials, which stimulate neuronal cell proliferation, migration and increase cell-material interaction to facilitate nerve regeneration across these critical-sized defects. This article briefly reviews several up-to-date published studies using Arginine-Glycine-Aspartic acid peptide sequence, nanocomposite based on polyhedral oligomeric silsesquioxane nanoparticle and nanofibrous scaffolds as promising strategies to enhance peripheral nerve regeneration by influencing cellular behaviour such as attachment, spreading and proliferation. The aim is to establish the potent manipulations, which are simple and easy to employ in the clinical conditions for nerve regeneration and repair. © 2015, Editorial Board of Neural Regeneration Research. All rights reserved.
... Our main interest lay in bioabsorbable biomaterials, polyhedral oligomeric silsesquioxane poly(e-caprolactone) urea urethane, (POSS-PCL) [12] that can support relevant cell growth whilst providing suitable mechanical properties (SI Image). POSS-PCL is also a highly insulating material (10 -13 S cm -1 ) and incorporation of POSS has attributed greater mechanical properties over pristine PCL. ...
Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content.
Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS–PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS–PCL and a new lamination method was explored. Porogen (40, 60 or 105 µm) were introduced to POSS–PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS–PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 µm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS–PCL. These bilayered-tubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored.
Porous polyethylene (pPE) is a frequently implanted biomaterial in craniofacial reconstructive surgery. Its rapid vascularization and tissue incorporation are major prerequisites to prevent complications, such as material infection, migration and extrusion. To achieve this, several sophisticated strategies have been introduced and evaluated during the last 20 years. These include i) the angiogenic stimulation of the host tissue with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) or macrophage-activating lipopeptide-2 (MALP-2), ii) material modifications, such as increase of surface roughness and incorporation of bioactive glass particles, iii) surface coatings with growth factors, glycoproteins, acrylic acid (AA), arginine-glycine-aspartic acid (RGD) peptide as well as components of the plasminogen activation system and autologous clotted blood or serum, and iv) the seeding with fibroblasts, chondrocytes, stem cells or adipose-tissue derived microvascular fragments (MVF). The majority of these approaches showed promising results in experimental studies and, thus, may be capable of improving the success rates after pPE implantation in future clinical practice.
Electrically-conductive nanocrystalline carbon films, having non-toxic and non-immunogenic characteristics, are promising candidates for reusable medical devices. Here, the pure and N- doped nanocrystalline carbon films are deposited by the assistance of inductively coupled plasma (ICP) in an unbalanced facing target pulsed-DC magnetron sputtering process. Through the optical emission spectroscopy study, the role of ICP assistance and N-doping on the reactive components/radicals during the synthesis is presented. The N-doping enhances the three fold bonding configurations by increasing the ionization and energies of the plasma species. Whereas, the ICP addition increases the plasma density to control the deposition rate and film structure. As a result, sputtering-throughput (deposition rate: 31–55 nm/min), electrical resistivity (4–72 Ωcm) and water contact angle (45.12°–54°) are significantly tailored. Electric transport study across the surface microchannel confirms the superiority of N-doped carbon films for sterilization stability over the undoped carbon films.
