Novel synthesis strategies for natural polymer and composite biomaterials as potential scaffolds for tissue engineering

Abstract

Recent developments in tissue engineering approaches frequently revolve around the use of three-dimensional scaffolds to function as the template for cellular activities to repair, rebuild and regenerate damaged or lost tissues. While there are several biomaterials to select as three-dimensional scaffolds, it is generally agreed that a biomaterial to be used in tissue engineering needs to possess certain material characteristics such as biocompatibility, suitable surface chemistry, interconnected porosity, desired mechanical properties and biodegradability. The use of naturally derived polymers as three-dimensional scaffolds has been gaining widespread attention owing to their favourable attributes of biocompatibility, low cost and ease of processing. This paper discusses the synthesis of various polysaccharide-based, naturally derived polymers, and the potential of using these biomaterials to serve as tissue engineering three-dimensional scaffolds is also evaluated. In this study, naturally derived polymers, specifically cellulose, chitosan, alginate and agarose, and their composites, are examined. Single-component scaffolds of plain cellulose, plain chitosan and plain alginate as well as composite scaffolds of cellulose-alginate, cellulose-agarose, cellulose-chitosan, chitosan-alginate and chitosan-agarose are synthesized, and their suitability as tissue engineering scaffolds is assessed. It is shown that naturally derived polymers in the form of hydrogels can be synthesized, and the lyophilization technique is used to synthesize various composites comprising these natural polymers. The composite scaffolds appear to be sponge-like after lyophilization. Scanning electron microscopy is used to demonstrate the formation of an interconnected porous network within the polymeric scaffold following lyophilization. It is also established that HeLa cells attach and proliferate well on scaffolds of cellulose, chitosan or alginate. The synthesis protocols reported in this study can therefore be used to manufacture naturally derived polymer-based scaffolds as potential biomaterials for various tissue engineering applications.

Figure 1.

Cellulose-based hydrogel synthesized with a mixture of CMC and HEC at a weight ratio of 3:1.

Figure 2.

Images showing the thermosensitive transition of Ultrasan from liquid to gel as a function of time.

Figure 3.

Alginate gel formed by the cross-linking of alginate solution with CaCl₂.

Figure 4.

Images of scaffolds of (a) pure cellulose, and composite scaffolds of (b) cellulose–alginate, (c) cellulose–agarose, (d) chitosan–cellulose, (e) chitosan–agarose and (f) chitosan–alginate.

Figure 5.

Cross-sectional SEM images of (a,b) cellulose scaffolds, (c) cellulose–agarose, (d) chitosan–cellulose, (e) chitosan–alginate and (f) chitosan–agarose, showing the porosity induced by lyophilization.

Figure 6.

Optical microscopy of (a) cellulose scaffold cross-linked with DVS, demonstrating the porous polymeric network (20×), (b) HeLa cells cultured on cellulose (10×), and (c) HeLa cells cultured on cellulose (20×).

Figure 7.

Optical microscopy images of HeLa cells cultured on (a) polystyrene, 2 days (20×), (b) Ultrasan, 91% DDA, 2 days (20×), (c) Ultrasan, 81% DDA, 2 days (20×), and (d) non-Ultrasan chitosan, 75% DDA, 3 days (10×).

Figure 8.

Optical microscopy image of HeLa cells cultured on alginate-based scaffold (10×).