Bioactive polymeric scaffolds for tissue engineering

Abstract

A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Keywords: Bioactive; Biodegradable; Biomaterials; Porosity; Scaffold; Tissue regeneration.

Graphical abstract

Fig. 1

There is always a tradeoff between mechanical strength and porosity, which must be fine-tuned depending on the tissue in question and the specific application.

Fig. 2

The surface morphology of typical PLLA nanofibrous scaffolds can be seen using SEM microscopy . The fibers represented indicate pure PLLA (a), PLLA with 2%Rg3 (b), PLLA with 6% Rg3 (c), and PLLA with 10% Rg3 (d). Rg3 is used to enhance the scaffold bioactivity as the compound plays a critical role in scar reduction, making such a material more useful for skin regeneration applications. It can be seen that the fibers are relatively uniform as well in structure, allowing for cellular infiltration of the scaffolds.

Fig. 3

A typical collagen scaffold is shown above, where (A) is the scaffold with 8 mm diameter and 2 mm thickness and (B) is a surface view (left) via SEM technology and a cross sectional view (right) . Scaffolds have an average pore size of about 80 μm and were fabricated with the use of a lyophilizer in order to create the porous structures shown. The rough surface morphology associated with many collagen type II scaffolds can be seen.

Fig. 4

Cellular staining for collagen type II and aggrecan markers demonstrates cellular viability on photo-crosslinked HA scaffolds in vitro for cartilage tissue engineering applications . Collagen type II and aggrecan are important byproducts for demonstrating cellular viability in many applications. One can observe the secretion of collagen and aggrecan markers as the amount of crosslinking is increased throughout the scaffold. It can also be observed that collagen type II and aggrecan markers are more concentrated at the edge of the constructs rather than towards the center.

Fig. 5

A typical chitosan-collagen composite microstructure is shown above using SEM technology . Part (A) is a zoomed out image of the structure, while (B) demonstrates the spherical nature of the microparticles. Part (C) displays the honey-bomb structure, while parts (D), (E), and (F) display the unique orientation of the micro-channels throughout the structure, which are formed by interconnected microparticles.

Fig. 6

A 3D printed brain model is shown . Part (A) shows a sagittal view of the brain from an MRI scan, (B) shows the rendered digital image, (C) shows the 3D printed result, and (D) shows electrical stimulation of the model. The model can be electrically stimulated in vitro for cell studies, albeit being able to replicate the functionality of the human brain in its entirety is still a very long way.

Fig. 7

Nanofiber morphology via SEM is shown . Part (A) shows the superfine diameter of the fibers, while (B) and (C) demonstrate the morphology before and after dipping in aqueous solution respectively. Polystyrene (PS) is used as a material. Through inspection, it can be visually noted that the fibers are of a uniform diameter, which is important for cellular compatibility.

Fig. 8

A typical PGA/Collagen NGC is shown above . Part (A) shows a digital image of the conduit, with (B) and (C) demonstrating how it fits into a nerve gap. The broken nerve has two cut ends and the tube fits directly between them, allowing for further outgrowth toward the gap itself.

Fig. 9

Silk fibroin scaffolds were stained with GFP at 8 weeks post in vivo operation . Part (a) represents pure silk, (b) is cell proliferation on the scaffold, (c) shows silk with VEGF and BMP-2 growth factors for vascularization, and (d) demonstrates cellular proliferation once again. New vasculature can be seen forming via VEGF stimulation.