Surface modification of polycaprolactone nanofibers through hydrolysis and aminolysis: a comparative study on structural characteristics, mechanical properties, and cellular performance.

Hydrolysis and aminolysis are two main commonly used chemical methods for surface modification of hydrophobic tissue engineering scaffolds. The type of chemical reagents along with the concentration and treatment time are main factors that determine the effects of these methods on biomaterials. In the present study, electrospun poly (ℇ-caprolactone) (PCL) nanofibers were modified through hydrolysis and aminolysis. The applied chemical solutions for hydrolysis and aminolysis were NaOH (0.5-2 M) and hexamethylenediamine/isopropanol (HMD/IPA, 0.5-2 M) correspondingly. Three distinct incubation time points were predetermined for the hydrolysis and aminolysis treatments. According to the scanning electron microscopy results, morphological changes emerged only in the higher concentrations of hydrolysis solution (1 M and 2 M) and prolonged treatment duration (6 and 12 h). In contrast, aminolysis treatments induced slight changes in the morphological features of the electrospun PCL nanofibers. Even though surface hydrophilicity of PCL nanofibers was noticeably improved through the both methods, the resultant influence of hydrolysis was comparatively more considerable. As a general trend, both hydrolysis and aminolysis resulted in a moderate decline in the mechanical performance of PCL samples. Energy dispersive spectroscopy analysis indicated elemental changes after the hydrolysis and aminolysis treatments. However, X-ray diffraction, thermogravimetric analysis, and infrared spectroscopy results did not show noticeable alterations subsequent to the treatments. The fibroblast cells were well spread and exhibited a spindle-like shape on the both treated groups. Furthermore, according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the surface treatment procedures ameliorated proliferative properties of PCL nanofibers. These findings represented that the modified PCL nanofibrous samples by hydrolysis and aminolysis treatments can be considered as the potentially favorable candidates for tissue engineering applications.

Tailoring structural properties, mechanical behavior and cellular performance of collagen hydrogel through incorporation of cellulose nanofibrils and cellulose nanocrystals: A comparative study.

Physically cross-linked collagen hydrogel is a desirable scaffold for tissue engineering applications especially where 3D cell encapsulation is considered. To overcome its shortcomings such as weak mechanical properties and also provide additional benefits, nanofiller reinforcement could be applied. This study was conducted to compare physical properties and cellular performance of physically cross-linked collagen hydrogel reinforced with cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs). Addition of both nanofillers drastically changed the hydrogel properties depending on the type and concentration. As a general trend, both CNCs and CNFs resulted in reduction in gelation time, enhancement in compressive strength, increase in swelling ratio, decrease in weight loss and improvement of injectability. The highest impact for CNCs was achieved when 5 % was applied, while the maximum impact for CNFs was observed for 3 % content (related to the collagen solid weight). By comparing two types of nanocellulose, CNCs showed higher impact on all properties. In-vitro cell compatibility with fibroblasts showed that CNFs did not adversely affected the viability and morphology of the cells while the CNCs improved cell viability and developed more elongated cell morphology.

Mitochondrial Targeted Peptide (KLAKLAK)2, and its Synergistic Radiotherapy Effects on Apoptosis of Radio Resistant Human Monocytic Leukemia Cell Line.

BACKGROUND: Ionizing radiation plays a significant role in cancer treatment. Despite recent advances in radiotherapy approaches, the existence of irradiation-resistant cancer cells is still a noteworthy challenge. Therefore, developing novel therapeutic approaches are still warranted in order to increase the sensitivity of tumor cells to radiation. Many types of research rely on the role of mitochondria in radiation protection. OBJECTIVE: Here, we aimed to target the mitochondria of monocyticleukemia (THP-1) radio-resistant cell line cells by a mitochondrial disrupting peptide, D (KLAKLAK)2, and investigate the synergistic effect of Gamma-irradiation and KLA for tumor cells inhibition in vitro. MATERIAL AND METHODS: In this experimental study, KLA was delivered into THP-1 cells using a Cell-Penetrating Peptide (CPP).The cells were then exposed to gamma-ray radiation both in the presence and absence of KLA conjugated with CPP. The impacts of KLA, ionizing radiation or combination of both were then evaluated on the cell proliferation and apoptosis of THP-1 cells using MTT assay and flow cytometry, respectively. RESULTS: The MTT assay indicated the anti-proliferative effects of combined D (KLAKLAK)2 peptide with ionizing radiation on THP-1cells. Moreover, synergetic effects of KLA and ionizing radiation reduced cell viability and consequently enhanced cell apoptosis. CONCLUSION: Using KLA peptide in combination with ionizing irradiation increases the anticancer effects of radio-resistant THP-1 cells. Therefore, the combinational therapy of (KLAKLAK)2 and radiation is a promising strategy for cancer treatment the in future.

Dual spinneret electrospun nanofibrous/gel structure of chitosan-gelatin/chitosan-hyaluronic acid as a wound dressing: In-vitro and in-vivo studies.

Structural and compositional similarity to the natural extracellular matrix (ECM) is a main characteristic of an ideal scaffold for tissue regeneration. In order to resemble the fibrous/gel structure of skin ECM, a multicomponent scaffold was fabricated using biopolymers with structural similarity to ECM and wound healing properties i.e., chitosan (CS), gelatin (Gel) and hyaluronic acid (HA). The CS-Gel and CS-HA nanofibers were simultaneously electrospun on the collector through dual-electrospinning technique. The presence of polymers, possible interactions, and formation of polyelectrolyte complex were proven by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and thermogravimetric analysis (TGA). The noncomplex component of CS-HA fibers formed a gel state when the scaffold was exposed to the aqueous media, while the CS-Gel fibers reserved their fibrous structure, resulting in formation of fibrous/gel structure. The CS-Gel/CS-HA scaffold showed significantly higher cell proliferation (109%) in the first 24 h comparing with CS (90%) and CS-Gel (96%) scaffolds. Additionally, the initial cell adhesion improved by incorporation of HA. The in-vivo wound healing results in rat elucidated more wound healing capability of the CS-Gel/CS-HA scaffold in which new tissue with most similarity to the normal skin was formed.

Stabilization of chitosan based electrospun nanofibers through a simple and safe method.

A simple and safe method was used to stabilize nanofibrous structure of chitosan (CS) based mats obtained from acidic solution. The electrospun CS based nanofibrous mats were fabricated using CS/poly ethylene oxide in acetic acid aqueous solution. Exposure to water vapor at 40-70 °C for 30-120 min was implemented in order to stabilizing the CS mats. Scanning electron microscopy of the treated mats revealed preservation of nanofibrous structure after immersion in phosphate buffered saline (pH = 7.4). This result along with infrared spectroscopy and thermogravimetric analysis confirmed removal of acetic acid residues and neutralization of CS mats after treatment with water vapor. Stabilization with water vapor also led to augmentation in tensile strength and elastic moduli of CS mats comparing to as-spun mats while the elongation was decreased. Furthermore, the crystallinity and thermal stability of mats were slightly increased after neutralization. In comparison with glutaraldehyde cross-linked mats, water vapor treated mats showed higher swelling ratio and enhanced cell compatibility.

Incorporation of nanofibrillated chitosan into electrospun PCL nanofibers makes scaffolds with enhanced mechanical and biological properties.

Fabricating polycaprolactone (PCL) composite can be a facile approach to improve wettability, mechanical properties and cellular compatibility of PCL-based scaffolds. In this study, nanofibrillated chitosan (NC) was utilized as dispersing phase in PCL matrix to acquire electrospun nanocomposite fibrous scaffolds. Various amounts of NC were added to PCL solutions and the solutions were electrospun under constant electrospinning parameters. Adding NC to PCL solutions was accompanied with notable changes in the solutions viscosity, conductivity and electrospinnability. Whiles the pure PCL solutions with concentration of 8 wt. % and 10 wt. % were not electrospinnable, adding 5-10 % NC made them electrospinnable. The mechanical properties, wettability and cellular compatibility of electrospun PCL/NC composites were improved as well. PCL/NC scaffolds showed remarkable enhancement in both tensile strength and Young's modulus compared to neat PCL scaffold. Contact angle measurements revealed improvement in wettability of scaffolds after adding NC. In addition, proliferation and adhesion of cells was enhanced when NC was incorporated to nanofibers. The results suggest PCL/NC as a proper scaffold for tissue engineering applications.

Evaluation of electrospinning parameters on the tensile strength and suture retention strength of polycaprolactone nanofibrous scaffolds through surface response methodology.

Scaffolds should provide sufficient biomechanical support during tissue regeneration for tissue engineering (TE) applications. Electrospun scaffolds are commonly applied in TE applications due to their tunable physical, chemical, and mechanical properties as well as their similarity to extracellular matrix. Although the mechanical properties of electrospun scaffolds are highly dependent on processing parameters, a limited number of studies have systematically investigated this subject. The present study has investigated the effects of the main electrospinning parameters on tensile and suture retention strength of polycaprolactone (PCL) scaffolds using response surface methodology. Scaffolds morphology and cell-scaffold interaction were also investigated in this study. According to the fitted model, polymer concentration and feed rate have the most significant positive effect on both the tensile and suture retention strength. Whereas applied voltage negatively affected both the tensile and suture retention strength. The effect of distance on tensile strength was not significant while its effect on suture retention was different depending on its values. Changes in biomechanical properties were associated with gross alterations in morphology of the fibers and cell-scaffold interaction. Scaffolds with lowest tensile strength presented a beaded morphology while scaffolds with higher tensile strength presented beadless morphology with worm-like fibers. The increase in tensile strength was correlated with the increase in average diameter of the fibers and pore size. The results of cell culture study showed that fibroblasts stretched and proliferated more on scaffolds with lower tensile strength. The generated model might be helpful when PCL scaffold with desirable tensile and suture retention strength are required. Furthermore, the results suggest that changes in morphology and subsequent cell-scaffold interaction should be considered when these biomechanical properties are optimized.