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PSIDAB fibrous membrane before (a) and after hydrolysis (b), where red numbers are the area of samples. https://doi.org/10.1371/journal.pone.0254843.g003
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In this work two types of biodegradable polysuccinimide-based, electrospun fibrous membranes are presented. One contains disulfide bonds exhibiting a shorter (3 days) in vivo biodegradation time, while the other one has alkyl crosslinks and a longer biodegradation time (more than 7 days). According to the mechanical measurements, the tensile streng...
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Context 1
... caused minimal change in the fiber morphology, which alterations should not have any effect on either the mechanical or in vivo performance of the membranes. An example for the macroscopic changes of a PSIDAB-PASPDAB transition can be seen in Fig 3. In this case, the fibrous membranes grew from 16 ± 0 mm to 21 ± 1 mm, which corresponds to 31 ± 7% (n = 3, p = 0.05). Similar behavior was demonstrated for PSI based bulk hydrogels [42] but also other PASP based fibrous membranes with different crosslinkers as well [27]. ...
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... both sample types grew by approximately 40% in diameter (from 16 mm to ~ 22 mm) and turned from the implanted white paper-like membranes to soft swollen gels (Figs 6A, 7A and 7B). Similar size change (16 mm to ~21 mm) due to hydrolysis was observed in vitro for both samples (Fig 3A and 3B, PSICYS not shown). This strongly suggests that hydrolysis of PSI based systems occurs in vivo, which is the first step in the biodegradation of PSI based materials. ...
Citations
... Synthetic poly(amino acid)s as degradable and water-soluble polymers are potential alternatives for fossil-based synthetic polymers and natural polymers due to their biomass origin and chemical versatility [28]. Poly (aspartic acid), a synthetic poly(amino acid), has high potential in biotechnology [29] and biomedical applications [30,31] such as drug delivery vehicles [32][33][34][35], film coatings [36], electrospun matrices [37,38], and scaffolding materials [39]. Its versatility is based on the reactivity of its precursor anhydride, polysuccinimide (PSI). ...
Efficient topical treatment of ocular diseases requires a prolonged residence time of drug formulations. An in situ gelling, mucoadhesive system can provide improved residence time while keeps the installation of the formulation easy and accurate due to its low initial viscosity. We synthesized a two-component, biocompatible water-based liquid formulation showing in situ gelation upon mixing. S-protected, preactivated derivatives of thiolated poly(aspartic acid) (PASP-SS-MNA) were synthesized by coupling the free thiol groups of thiolated poly(aspartic acid) (PASP-SH) with 6-mercaptonicotinic acid (MNA). The amount of protecting groups was 242, 341, and 530 µmol/g depending on the degree of thiolation of PASP. The chemical interaction between PASP-SS-MNA and mucin was proven, indicating the mucoadhesive properties. Disulfide cross-linked hydrogels were formed in situ without an oxidizing agent by mixing the aqueous solutions of PASP-SS-MNA and PASP-SH. The gelation time was controlled between 1 and 6 min, while the storage modulus was as high as 4-16 kPa depending on the composition. Swelling experiments showed that hydrogels with no residual thiol groups are stable in phosphate-buffered saline at pH = 7.4. In contrast, the presence of free thiol groups leads to the dissolution of the hydrogel with a rate depending on the excess of thiol groups. The biological safety of the polymers and MNA was confirmed on Madin-Darby Canine Kidney cell line. Furthermore, a prolonged release of ofloxacin was observed at pH = 7.4 compared to a conventional liquid formulation, supporting the potential of the developed biopolymers in ophthalmic drug delivery.
... Magnetic iron oxide nanoparticles (MIONPs) are highly promising candidates for theranostics [7][8][9][10][11][12]. Being superparamagnetic nanoparticles [13,14] their magnetic momentum turns towards an external magnetic field and thus act as nanomagnets. ...
... Polysuccinimide (PSI) is a cyto-and biocompatible polymer. It hydrolyses in vivo to poly(aspartic acid) (PASP), which can then be eliminated via renal secretion and bowel excretion [7,8,14]. Thus, after a potential implantation, not only nanoparticles, but also the implant, will be eliminated [9]. ...
... Thus, after a potential implantation, not only nanoparticles, but also the implant, will be eliminated [9]. Electrospun PSI systems have been documented and their physico-chemical properties are more than suitable for implantation, while their biodegradation period can be adjusted days, weeks or months [7]. ...
When exposed to an alternating magnetic field, superparamagnetic nanoparticles can elicit the required hyperthermic effect while also being excellent magnetic resonance imaging (MRI) contrast agents. Their main drawback is that they diffuse out of the area of interest in one or two days, thus preventing a continuous application during the typical several-cycle multi-week treatment. To solve this issue, our aim was to synthesise an implantable, biodegradable membrane infused with magnetite that enabled long-term treatment while having adequate MRI contrast and hyperthermic capabilities. To immobilise the nanoparticles inside the scaffold, they were synthesised inside hydrogel fibres. First, polysuccinimide (PSI) fibres were produced by electrospinning and crosslinked, and then, magnetitc iron oxide nanoparticles (MIONs) were synthesised inside and in-between the fibres of the hydrogel membranes with the well-known co-precipitation method. The attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) investigation proved the success of the chemical synthesis and the presence of iron oxide, and the superconducting quantum interference device (SQUID) study revealed their superparamagnetic property. The magnetic hyperthermia efficiency of the samples was significant. The given alternating current (AC) magnetic field could induce a temperature rise of 5 °C (from 37 °C to 42 °C) in less than 2 min even for five quick heat-cool cycles or for five consecutive days without considerable heat generation loss in the samples. Short-term (1 day and 7 day) biocompatibility, biodegradability and MRI contrast capability were investigated in vivo on Wistar rats. The results showed excellent MRI contrast and minimal acute inflammation.
... During this process, a non-woven mat can be produced consisting of polymer fibers with a diameter on nanometer-or micrometer scale. Plenty of publications have recently appeared in the field of nanotechnology and tissue engineering regarding electrospun fibrous structures using biopolymers such as collagen [4] and gelatin [5], or synthetic polymers such as polycaprolactone [6], polyvinylpyrollidon [7] or synthetic biopolymers such as poly-Llacticacid [8], and polyamino acids [9] separately, or in combination [10]. ...
... Cytotoxicity tests were carried out as described in our previous studies [38], [9], ...
... The size of the images was 1.6 μm x 1.6 μm and they were taken by the MES 4.4v program. The low red channel (600-700 nm) was used to detect the red fluorescence of the cells due to the Vybrant DiD vital staining while the low green channel (490-560 nm) was used to detect the autofluorescence of the PASPDAB membranes [9]. After image capturing, the ImageJ program was used for further modifications. ...
The aim of tissue engineering is to develop methods to restore, maintain or improve tissue functions. To imitate the fibrous structure of the native extracellular matrix, the electrospinning technique is widely used. However, the dense packing of fibers results in small pores and hereby the inhibition of cellular penetration.
In this study, we used biocompatible and biodegradable poly(aspartic acid) based fibrous hydrogel scaffolds to enhance the cell infiltration using ultrasonication (US). The US can enlarge the space between the fibers in the scaffold and create a 3D structure based on the thickness increase of the samples. To prevent the scaffolds from degradation and create an easy-to-store sample beyond the US treatment, a freeze-drying process was also introduced in this work. After all these treatments, the scaffold’s specific load capacity was 0.11 ± 0.01 Nm²/g which did not change after a rehydration cycle and the elongation break became almost two times higher than before the US treatment. The cytotoxicity results demonstrated that the cellular viability did not show any significant decrease compared to the control groups for none of the samples. The cellular penetration was visualized by multiphoton microscopy.
In summary, we were able to overcome the major limitation of conventional electrospun scaffolds regarding their application in tissue engineering. We also improved the storing conditions of fibrous hydrogel scaffolds and extend their shelf life without degradation.
... In parallel research we work on the development of scaffolds that allow not only the survival and proliferation of the ectomesenchyme-derived cells, both in vitro and in vivo, but also elicit their differentiation [64][65][66][67][68]. By chemical modification of biocompatible and biodegradable poly(aspartamide) (PASP)-based hydrogels, and parallel studies on their biocompatibility, biodegradability and regenerative potential, we are attempting to develop novel scaffolds that are clinically applicable [64][65][66][67][68]. ...
... In parallel research we work on the development of scaffolds that allow not only the survival and proliferation of the ectomesenchyme-derived cells, both in vitro and in vivo, but also elicit their differentiation [64][65][66][67][68]. By chemical modification of biocompatible and biodegradable poly(aspartamide) (PASP)-based hydrogels, and parallel studies on their biocompatibility, biodegradability and regenerative potential, we are attempting to develop novel scaffolds that are clinically applicable [64][65][66][67][68]. We expect that in the near future these separate lines of research, on microcarriers and scaffolds, will meet through the development of biomaterials that can serve both for cell expansion and tissue regeneration. ...
Ectomesenchymal stem cells derived from the dental pulp are of neural crest origin, and as such are promising sources for cell therapy and tissue engineering. For safe upscaling of these cells, microcarrier-based culturing under dynamic conditions is a promising technology. We tested the suitability of two microcarriers, non-porous Cytodex 1 and porous Cytopore 2, for culturing well characterized dental pulp stem cells (DPSCs) using a shake flask system. Human DPSCs were cultured on these microcarriers in 96-well plates, and further expanded in shake flasks for upscaling experiments. Cell viability was measured using the alamarBlue assay, while cell morphology was observed by conventional and two-photon microscopies. Glucose consumption of cells was detected by the glucose oxidase/Clark-electrode method. DPSCs adhered to and grew well on both microcarrier surfaces and were also found in the pores of the Cytopore 2. Cells grown in tissue culture plates (static, non-shaking conditions) yielded 7 × 105 cells/well. In shake flasks, static preincubation promoted cell adhesion to the microcarriers. Under dynamic culture conditions (shaking) 3 × 107 cells were obtained in shake flasks. The DPSCs exhausted their glucose supply from the medium by day seven even with partial batch-feeding. In conclusion, both non-porous and porous microcarriers are suitable for upscaling ectomesenchymal DPSCs under dynamic culture conditions.
Bacterial infection caused by medical material is a common problem in the field of medicine. In this work, we aim to develop a novel antimicrobial bioplastic with potential medical value. A novel composite material composed of polyamino acid (PAA) and titanium dioxide/silver nanoparticles (TiO 2 /Ag NPs) was synthesized by in situ melting polycondensation with different TiO 2 /Ag loadings. The morphological, antibacterial, mechanical, thermal, and cytotoxicity properties of the PAA/TiO 2 /Ag composites were investigated. The results showed that uniform nanocomposites with amide bonds were synthesized, and the nanocomposites with 10% TiO 2 /Ag incorporation exhibited the best thermal and mechanical properties. Cytotoxicity assay showed that the composites significantly promoted the proliferation of MG‐63 cells. The composites showed obvious inhibitory effect on both Escherichia coli and Staphylococcus aureus , and this effect was increased as the TiO 2 /Ag NPs doping was increased. These PAA/TiO 2 /Ag composites are suitable for antibacterial and high‐performance biomaterials in the medical field.
