Directing Axonal Growth: A Review on the Fabrication of Fibrous Scaffolds That Promotes the Orientation of Axons

Gels ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 25
Author(s):  
Devindraan Sirkkunan ◽  
Belinda Pingguan-Murphy ◽  
Farina Muhamad

Tissues are commonly defined as groups of cells that have similar structure and uniformly perform a specialized function. A lesser-known fact is that the placement of these cells within these tissues plays an important role in executing its functions, especially for neuronal cells. Hence, the design of a functional neural scaffold has to mirror these cell organizations, which are brought about by the configuration of natural extracellular matrix (ECM) structural proteins. In this review, we will briefly discuss the various characteristics considered when making neural scaffolds. We will then focus on the cellular orientation and axonal alignment of neural cells within their ECM and elaborate on the mechanisms involved in this process. A better understanding of these mechanisms could shed more light onto the rationale of fabricating the scaffolds for this specific functionality. Finally, we will discuss the scaffolds used in neural tissue engineering (NTE) and the methods used to fabricate these well-defined constructs.

Nanomaterials ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 952 ◽  
Author(s):  
Li ◽  
Liao ◽  
Tjong

Polyvinylidene fluoride (PVDF) and polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE) with excellent piezoelectricity and good biocompatibility are attractive materials for making functional scaffolds for bone and neural tissue engineering applications. Electrospun PVDF and P(VDF-TrFE) scaffolds can produce electrical charges during mechanical deformation, which can provide necessary stimulation for repairing bone defects and damaged nerve cells. As such, these fibrous mats promote the adhesion, proliferation and differentiation of bone and neural cells on their surfaces. Furthermore, aligned PVDF and P(VDF-TrFE) fibrous mats can enhance neurite growth along the fiber orientation direction. These beneficial effects derive from the formation of electroactive, polar β-phase having piezoelectric properties. Polar β-phase can be induced in the PVDF fibers as a result of the polymer jet stretching and electrical poling during electrospinning. Moreover, the incorporation of TrFE monomer into PVDF can stabilize the β-phase without mechanical stretching or electrical poling. The main drawbacks of electrospinning process for making piezoelectric PVDF-based scaffolds are their small pore sizes and the use of highly toxic organic solvents. The small pore sizes prevent the infiltration of bone and neuronal cells into the scaffolds, leading to the formation of a single cell layer on the scaffold surfaces. Accordingly, modified electrospinning methods such as melt-electrospinning and near-field electrospinning have been explored by the researchers to tackle this issue. This article reviews recent development strategies, achievements and major challenges of electrospun PVDF and P(VDF-TrFE) scaffolds for tissue engineering applications.


2012 ◽  
Vol 1 (6) ◽  
pp. 681-681 ◽  
Author(s):  
Mohammad R. Abidian ◽  
Eugene D. Daneshvar ◽  
Brent M. Egeland ◽  
Daryl R. Kipke ◽  
Paul S. Cederna ◽  
...  

Biomaterials ◽  
2014 ◽  
Vol 35 (4) ◽  
pp. 1205-1214 ◽  
Author(s):  
Silvia Baiguera ◽  
Costantino Del Gaudio ◽  
Elena Lucatelli ◽  
Elena Kuevda ◽  
Margherita Boieri ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3876
Author(s):  
Diana María Osorio-Londoño ◽  
José Rafael Godínez-Fernández ◽  
Ma. Cristina Acosta-García ◽  
Juan Morales-Corona ◽  
Roberto Olayo-González ◽  
...  

Promising strategies for neural tissue engineering are based on the use of three-dimensional substrates for cell anchorage and tissue development. In this work, fibrillar scaffolds composed of electrospun randomly- and aligned-oriented fibers coated with plasma synthesized pyrrole polymer, doped and undoped with iodine, were fabricated and characterized. Infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction analysis revealed the functional groups and molecular integration of each scaffold, as well as the effect of plasma polymer synthesis on crystallinity. Scanning microscopy imaging demonstrated the porous fibrillar micrometric structure of the scaffolds, which afforded adhesion, infiltration, and survival for the neural cells. Orientation analysis of electron microscope images confirmed the elongation of neurite-like cell structures elicited by undoped plasma pyrrole polymer-coated aligned scaffolds, without any biochemical stimuli. The MTT colorimetric assay validated the biocompatibility of the fabricated composite materials, and further evidenced plasma pyrrole polymer-coated aligned scaffolds as permissive substrates for the support of neural cells. These results suggest plasma synthesized pyrrole polymer-coated aligned scaffolds are promising materials for tissue engineering applications.


2012 ◽  
Vol 1 (6) ◽  
pp. 762-767 ◽  
Author(s):  
Mohammad R. Abidian ◽  
Eugene D. Daneshvar ◽  
Brent M. Egeland ◽  
Daryl R. Kipke ◽  
Paul S. Cederna ◽  
...  

2020 ◽  
Vol 17 (162) ◽  
pp. 20190505 ◽  
Author(s):  
Pallavi Madhusudanan ◽  
Gayathri Raju ◽  
Sahadev Shankarappa

Neural tissue engineering (NTE) is a rapidly progressing field that promises to address several serious neurological conditions that are currently difficult to treat. Selecting the right scaffolding material to promote neural and non-neural cell differentiation as well as axonal growth is essential for the overall design strategy for NTE. Among the varieties of scaffolds, hydrogels have proved to be excellent candidates for culturing and differentiating cells of neural origin. Considering the intrinsic resistance of the nervous system against regeneration, hydrogels have been abundantly used in applications that involve the release of neurotrophic factors, antagonists of neural growth inhibitors and other neural growth-promoting agents. Recent developments in the field include the utilization of encapsulating hydrogels in neural cell therapy for providing localized trophic support and shielding neural cells from immune activity. In this review, we categorize and discuss the various hydrogel-based strategies that have been examined for neural-specific applications and also highlight their strengths and weaknesses. We also discuss future prospects and challenges ahead for the utilization of hydrogels in NTE.


Author(s):  
Chun-Yi Yang ◽  
Wei-Yuan Huang ◽  
Liang-Hsin Chen ◽  
Nai-Wen Liang ◽  
Huan-Chih Wang ◽  
...  

Strategies using surface topography, contact guidance and biomechanical cues in the design of scaffolds as an ECM support for neural tissue engineering.


Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1205
Author(s):  
Ruchi Sharma ◽  
Rebecca Kirsch ◽  
Karolina Papera Valente ◽  
Milena Restan Perez ◽  
Stephanie Michelle Willerth

Three-dimensional bioprinting can fabricate precisely controlled 3D tissue constructs. This process uses bioinks—specially tailored materials that support the survival of incorporated cells—to produce tissue constructs. The properties of bioinks, such as stiffness and porosity, should mimic those found in desired tissues to support specialized cell types. Previous studies by our group validated soft substrates for neuronal cultures using neural cells derived from human-induced pluripotent stem cells (hiPSCs). It is important to confirm that these bioprinted tissues possess mechanical properties similar to native neural tissues. Here, we assessed the physical and mechanical properties of bioprinted constructs generated from our novel microsphere containing bioink. We measured the elastic moduli of bioprinted constructs with and without microspheres using a modified Hertz model. The storage and loss modulus, viscosity, and shear rates were also measured. Physical properties such as microstructure, porosity, swelling, and biodegradability were also analyzed. Our results showed that the elastic modulus of constructs with microspheres was 1032 ± 59.7 Pascal (Pa), and without microspheres was 728 ± 47.6 Pa. Mechanical strength and printability were significantly enhanced with the addition of microspheres. Thus, incorporating microspheres provides mechanical reinforcement, which indicates their suitability for future applications in neural tissue engineering.


2015 ◽  
Vol 1798 ◽  
Author(s):  
Rachel Martin ◽  
M. E. Mullins ◽  
F. Zhao ◽  
Zichen Qian

ABSTRACTPolymer nanofiber scaffolds for use in neural tissue engineering have been fabricated via electrospinning of poly-L-lactic acid (PLLA) directly onto a 3D printed support. Previously, the investigators have shown success in promoting the directed growth of neural axons on highly aligned PLLA substrates both in vitro and in vivo. However, one criticism of the earlier in vitro studies is that by spinning fibers on a flat, two-dimensional surface, the growth of the axons is restricted to one plane. Thus the axon-to-fiber attachment may not be the sole mechanism for aligning the growth of the axons along the fibers, and the channels between the fibers and the substrate could contribute to the results. Using 3D-printing, elevated or “bridge” spinning stages were made with supports at varying heights, allowing the fibers to be suspended 2 to 5 mm above the substrate surface in different configurations. This 3D structure promotes better access of in vitro cell cultures on the fibers to the growth media during incubation, reduces substrate effects, allows more degrees of freedom for axonal growth, and more closely simulates the growth environment found in vivo. Using these 3D stages, we have electrospun free-standing, highly-aligned pure PLLA fiber scaffolds. We are exploring spinning coaxial fibers with a PLLA sheath and a second core polymer. These coaxial fiber scaffold structures offer additional opportunities for in situ delivery of growth agents and/or electrical stimulation for improved axonal growth results.


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