Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery

Abstract

Natural bone constitutes a complex and organized structure of organic and inorganic components with limited ability to regenerate and restore injured tissues, especially in large bone defects. To improve the reconstruction of the damaged bones, tissue engineering has been introduced as a promising alternative approach to the conventional therapeutic methods including surgical interventions using allograft and autograft implants. Bioengineered composite scaffolds consisting of multifunctional biomaterials in combination with the cells and bioactive therapeutic agents have great promise for bone repair and regeneration. Cellulose and its derivatives are renewable and biodegradable natural polymers that have shown promising potential in bone tissue engineering applications. Cellulose-based scaffolds possess numerous advantages attributed to their excellent properties of non-toxicity, biocompatibility, biodegradability, availability through renewable resources, and the low cost of preparation and processing. Furthermore, cellulose and its derivatives have been extensively used for delivering growth factors and antibiotics directly to the site of the impaired bone tissue to promote tissue repair. This review focuses on the various classifications of cellulose-based composite scaffolds utilized in localized bone drug delivery systems and bone regeneration, including cellulose-organic composites, cellulose-inorganic composites, cellulose-organic/inorganic composites. We will also highlight the physicochemical, mechanical, and biological properties of the different cellulose-based scaffolds for bone tissue engineering applications.

Keywords: Bone tissue engineering; Cellulose; Cellulose derivatives; Drug delivery system.

Graphical abstract

Fig. 1

Chemical formulation of cellulose and its derivatives [27].

Fig. 2

A. Schematic illustration for PLA/RC scaffold fabrication [51]. B. Calcium and phosphate nucleation by biomimetic method in PLA/RC scaffold [51]. C. 3D printed T-CNF/SA hydrogels in different forms [65]. D. 3D printed cell-encapsulated bio-ink was spontaneously gelled at 37 °C [71].

Fig. 3

A. Illustration of the fabricating regenerated cellulose fibers containing HAp and Ag NPs [133]. B. Schematic of creation of 3D carbon fiber reinforced CMC-HAp ternary composite [142].

Fig. 4

A. Schematic of preparation process of the BC-GEL/HAp hydrogel [158]. B. Schematic of stress dissipating of the BC-GEL/HAp composite under external load [158]. C. Schematic of the formation mechanism of Col-CMC/HAp composites [176].

Fig. 5

A. Preparation of PLA-EC/HAp porous scaffolds for bone grafting [187]. B. Bone grafting of PLA-EC/HAp porous scaffold [187]. C. Schematic of the TEMPO-oxidation of BC and the colloidal dispersion of HAp NPs. (HAp NPs/TOBC solutions with weight ratios of 1:1) [203].

Fig. 6

A. Schematic of different drug delivery systems based on cellulose for bone tissue engineering. B. The ALP activity of BC-BMP-2 scaffolds after implantation (BMP-2 at 225 mg/ml for L-BMP-2/BC, and BMP-2 at 450 mg/ml for H-BMP-2/BC) [214]. C. Cumulative release of ceftazidime from EC microspheres and HAp/PU scaffolds (microspheres/scaffold-L and microspheres/scaffold-H refers to EC microspheres incorporated HAp/PU scaffolds containing 100 μg and 200 μg ceftazidime, respectively) [223].