Covalently polysaccharide-based alginate/chitosan hydrogel embedded alginate microspheres for BSA encapsulation and soft tissue engineering

Hydrogels based scaffolds are very promising materials for a wide range of medical applications including tissue engineering and drug delivery. This study reports a covalently cross-linked composite hydrogel embedded with microspheres basing natural polysaccharides as a protein delivery system for soft tissue engineering. This biodegradable composite hydrogel derived from water-soluble chitosan and alginate derivatives upon mixing, without addition of chemical cross-linking agents. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of N-succinyl chitosan (N-Chi) and oxidized alginate (OAlg), respectively. Meanwhile, gel-like microspheres were prepared with a diameter of 2-10 μm by conjugating sodium alginate with Ca2+ in an aqueous emulsion via the emulsion cross-linking technique. Bull Serum Albumin (BSA) was encapsulated into alginate gel microspheres and subsequently incorporated into OAlg/N-Chi hydrogels to produce a composite scaffold. In the current work, gelation rate, morphology, mechanical properties, swelling ratio, in vitro degradation and BSA release of the composite scaffolds were examined. The results show that mechanical and stable properties of gel scaffolds can be significantly improved by embedding alginate microspheres. The alginate microspheres can serve as a filler to toughen the soft OAlg/N-Chi hydrogels. Compressive modulus of composite gel scaffolds containing 0.5 mL volume of microspheres was 57.3 KPa, which was higher than the control hydrogel without microspheres. Moreover, the controlled release of BSA encapsulated within this composite hydrogels showed significantly lower rate when compared with control hydrogel or microspheres alone. These characteristics provide a potential opportunity to use this injectable composite gel scaffold in protein delivery and soft tissue engineering applications.