Nor Hasrul Akhmal Ngadiman

γ-Fe2O3 nanoparticles filled polyvinyl alcohol as potential biomaterial for tissue engineering scaffold

Maghemite (γ-Fe2O3) nanoparticle with its unique magnetic properties is recently known to enhance the cell growth rate. In this study, γ-Fe2O3 is mixed into polyvinyl alcohol (PVA) matrix and then electrospun to form nanofibers. Design of experiments was used to determine the optimum parameter settings for the electrospinning process so as to produce elctrospun mats with the preferred characteristics such as good morphology, Youngs modulus and porosity. The input factors of the electrospinnning process were nanoparticles content (1-5%), voltage (25-35 kV), and flow rate (1-3 ml/h) while the responses considered were Youngs modulus and porosity. Empirical models for both responses as a function of the input factors were developed and the optimum input factors setting were determined, and found to be at 5% nanoparticle content, 35 kV voltage, and 1 ml/h volume flow rate. The characteristics and performance of the optimum PVA/γ-Fe2O3 nanofiber mats were compared with those of neat PVA nanofiber mats in terms of morphology, thermal properties, and hydrophilicity. The PVA/γ-Fe2O3 nanofiber mats exhibited higher fiber diameter and surface roughness yet similar thermal properties and hydrophilicity compared to neat PVA PVA/γ-Fe2O3 nanofiber mats. Biocompatibility test by exposing the nanofiber mats with human blood cells was performed. In terms of clotting time, the PVA/γ-Fe2O3 nanofibers exhibited similar behavior with neat PVA. The PVA/γ-Fe2O3 nanofibers also showed higher cells proliferation rate when MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was done using human skin fibroblast cells. Thus, the PVA/γ-Fe2O3 electrospun nanofibers can be a promising biomaterial for tissue engineering scaffolds.

A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions:

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

Development of highly porous biodegradable γ-Fe2O3/polyvinyl alcohol nanofiber mats using electrospinning process for biomedical application

The use of electrospinning process in fabricating tissue engineering scaffolds has received great attention in recent years due to its simplicity. The nanofibers produced via electrospinning possessed morphological characteristics similar to extracellular matrix of most tissue components. Porosity plays a vital role in developing tissue engineering scaffolds because it influences the biocompatibility performance of the scaffolds. In this study, maghemite (γ-Fe2O3) was mixed with polyvinyl alcohol (PVA) and subsequently electrospun to produce nanofibers. Five factors; nanoparticles content, voltage, flow rate, spinning distance, and rotating speed were varied to produce the electrospun nanofibrous mats with high porosity value. Empirical model was developed using response surface methodology to analyze the effect of these factors to the porosity. The results revealed that the optimum porosity (90.85%) was obtained using 5% w/v nanoparticle content, 35kV of voltage, 1.1ml/h volume flow rate of solution, 8cm spinning distance and 2455rpm of rotating speed. The empirical model was verified successfully by performing confirmation experiments. The properties of optimum PVA/γ-Fe2O3 nanofiber mats such as fiber diameter, mechanical properties, and contact angle were investigated. In addition, cytocompatibility test, in vitro degradation rate, and MTT assay were also performed. Results revealed that high porosity biodegradable γ-Fe2O3/polyvinyl alcohol nanofiber mats have low mechanical properties but good degradation rates and cytocompatibility properties. Thus, they are suitable for low load bearing biomedical application or soft tissue engineering scaffold.

Effect of Electrospinning Parameters Setting towards Fiber Diameter

Fabrication of nanofibers using electrospinning has recently attracted much attention for various applications due to its simplicity. Electrospinning has the ability to produce nanofibers within 100-500 nm. Some applications require certain fiber diameter. As a relatively new process, there are many electrospinning parameters that are believed to influence the nanofibers diameter. The purpose of this review is to identify and discuss the effect of some of those parameters, i.e. concentration, spinning distance, and applied voltage, and volume flow rate, to the nanofiber diameter during electrospinning process. It was concluded that fiber volume flow rate is proportional to fiber diameter while there is no agreement in reports on other parameters.

Mechanical properties and biocompatibility of co-axially electrospun polyvinyl alcohol/maghemite

Electrospinning is a simple and efficient process in producing nanofibers. To fabricate nanofibers made of a blend of two constituent materials, co-axial electrospinning method is an option. In this method, the constituent materials contained in separate barrels are simultaneously injected using two syringe nozzles arranged co-axially and the materials mix during the spraying process forming core and shell of the nanofibers. In this study, co-axial electrospinning method is used to fabricate nanofibers made of polyvinyl alcohol and maghemite (γ-Fe2O3). The concentration of polyvinyl alcohol and amount of maghemite nanoparticle loading were varied, at 5 and 10 w/v% and at 1–10 v/v%, respectively. The mechanical properties (strength and Young’s modulus), porosity, and biocompatibility properties (contact angle and cell viability) of the electrospun mats were evaluated, with the same mats fabricated by regular single-nozzle electrospinning method as the control. The co-axial electrospinning method is able to fabricate the expected polyvinyl alcohol/maghemite nanofiber mats. It was noticed that the polyvinyl alcohol/maghemite electrospun mats have lower mechanical properties (i.e. strength and stiffness) and porosity, more hydrophilicity (i.e. lower contact angle), and similar cell viability compared to the mats fabricated by single-nozzle electrospinning method.

Fabricating high mechanical strength γ-Fe2O3 nanoparticles filled poly(vinyl alcohol) nanofiber using electrospinning process potentially for tissue engineering scaffold

The use of electrospinning has gained substantial interest in the development of tissue engineering scaffolds due to its ability to produce nanoscale fibers which can mimic the geometry of extracellular tissues. Besides geometry, mechanical property is one of the main elements to be considered when developing tissue engineering scaffolds. In this study, the electrospinning process parameter settings were varied in order to find the optimum setting which can produce electrospun nanofibrous mats with good mechanical properties. Maghemite (γ-Fe2O3) was mixed with poly(vinyl alcohol) and then electrospun to form nanofibers. The five input variable factors involved were nanoparticles content, voltage, flow rate, spinning distance, and rotating speed, while the response variable considered was Young’s modulus. The performance of electrospinning process was systematically screened and optimized using response surface methodology. This work truly demonstrated the sequential nature of designed experimentation. Additionally, the application of various designs of experiment techniques and concepts was also demonstrated. Results revealed that electrospun nanofibrous mats with maximum Young’s modulus (273.51 MPa) was obtained at optimum input settings: 9 v/v% nanoparticle content, 35 kV voltage, 2 mL/h volume flow rate, 8 cm spinning distance, and 3539 r/min of rotating speed. The model was verified successfully by performing confirmation experiments. The nanofibers characterization demonstrated that the nanoparticles were well dispersed inside the nanofibers, and it also showed that the presence of defects on the nanofibers can decrease their mechanical strength. The biocompatibility performance was also evaluated and it was proven that the presence of γ-Fe2O3 enhanced the cell viability and cell growth rate. The developed poly(vinyl alcohol)/γ-Fe2O3 electrospun nanofiber mat has a good potential for tissue engineering scaffolds.

3D Biofabrication of Thermoplastic Polyurethane (TPU)/Poly-l-lactic Acid (PLLA) Electrospun Nanofibers Containing Maghemite (γ-Fe2O3) for Tissue Engineering Aortic Heart Valve

Valvular dysfunction as the prominent reason of heart failure may causes morbidity and mortality around the world. The inability of human body to regenerate the defected heart valves necessitates the development of the artificial prosthesis to be replaced. Besides, the lack of capacity to grow, repair or remodel of an artificial valves and biological difficulty such as infection or inflammation make the development of tissue engineering heart valve (TEHV) concept. This research presented the use of compound of poly-l-lactic acid (PLLA), thermoplastic polyurethane (TPU) and maghemite nanoparticle (γ-Fe2O3) as the potential biomaterials to develop three-dimensional (3D) aortic heart valve scaffold. Electrospinning was used for fabricating the 3D scaffold. The steepest ascent followed by the response surface methodology was used to optimize the electrospinning parameters involved in terms of elastic modulus. The structural and porosity properties of fabricated scaffold were characterized using FE-SEM and liquid displacement technique, respectively. The 3D scaffold was then seeded with aortic smooth muscle cells (AOSMCs) and biological behavior in terms of cell attachment and proliferation during 34 days of incubation was characterized using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal laser microscopy. Furthermore, the mechanical properties in terms of elastic modulus and stiffness were investigated after cell seeding through macro-indentation test. The analysis indicated the formation of ultrafine quality of nanofibers with diameter distribution of 178 ± 45 nm and 90.72% porosity. In terms of cell proliferation, the results exhibited desirable proliferation (109.32 ± 3.22% compared to the control) of cells over the 3D scaffold in 34 days of incubation. The elastic modulus and stiffness index after cell seeding were founded to be 22.78 ± 2.12 MPa and 1490.9 ± 12 Nmm2, respectively. Overall, the fabricated 3D scaffold exhibits desirable structural, biological and mechanical properties and has the potential to be used in vivo.

Novel Processing Technique to Produce Three Dimensional Polyvinyl Alcohol/Maghemite Nanofiber Scaffold Suitable for Hard Tissues

Fabrication of three dimensional (3D) tissue engineering scaffolds, particularly for hard tissues remains a challenge. Electrospinning has been used to fabricate scaffolds made from polymeric materials which are suitable for hard tissues. The electrospun scaffolds also have structural arrangement that mimics the natural extracellular matrix. However, electrospinning has a limitation in terms of scaffold layer thickness that it can fabricate. Combining electrospinning with other processes is the way forward, and in this proposed technique, the basic shape of the scaffold is obtained by a fused deposition modelling (FDM) three dimensional (3D) printing machine using the partially hydrolysed polyvinyl alcohol (PVA) as the filament material. The 3D printed PVA becomes a template to be placed inside a mould which is then filled with the fully hydrolysed PVA/maghemite (γ-Fe2O3) solution. After the content in the mould solidified, the mould is opened and the content is freeze dried and immersed in water to dissolve the template. The 3D structure made of PVA/maghemite is then layered by electrospun PVA/maghemite fibers, resulting in 3D tissue engineering scaffold made from PVA/maghemite. The morphology and mechanical properties (strength and stiffness) were analysed and in vitro tests by degradation test and cell penetration were also performed. It was revealed that internally, the 3D scaffold has milli- and microporous structures whilst externally; it has a nanoporous structure as a result of the electrospun layer. The 3D scaffold has a compressive strength of 78.7 ± 0.6 MPa and a Young’s modulus of 1.43 ± 0.82 GPa, which are within the expected range for hard tissue engineering scaffolds. Initial biocompatibility tests on cell penetration revealed that the scaffold can support growth of human fibroblast cells. Overall, the proposed processing technique which combines 3D printing process, thermal inversion phase separation (TIPS) method and electrospinning process has the potential for producing hard tissue engineering 3D scaffolds.