Cellulose-Based Hybrid Hydrogels for Tissue Engineering Applications: A Sustainable Approach

Abstract

Cellulose is a sustainable biopolymer, being renewable and abundant, non-toxic, biodegradable, and easily functionalizable. However, the development of hydrogels for tissue engineering applications presents significant challenges that require interdisciplinary expertise, given the intricate and dynamic nature of the human body. This paper delves into current research focused on creating advanced cellulose-based hydrogels with tailored mechanical, biological, chemical, and surface properties. These hydrogels show promise in healing, regenerating, and even replacing human tissues and organs. The synthesis of these hydrogels employs a range of innovative techniques, including supramolecular chemistry, click chemistry, enzyme-induced crosslinking, ultrasound, photo radiation, high-energy ionizing radiation, 3D printing, and other emerging methods. In the realm of tissue engineering, various types of hydrogels are explored, such as stimuli-responsive, hybrid, injectable, bio-printed, electrospun, self-assembling, self-healing, drug-releasing, biodegradable, and interpenetrating network hydrogels. Moreover, these materials can be further enhanced by incorporating cell growth factors, biological molecules, or by loading them with cells or drugs. Looking ahead, future research aims to engineer and tailor hydrogels to meet specific needs. This includes exploring safer and more sustainable materials and synthesis techniques, identifying less invasive application methods, and translating these studies into practical applications.

Keywords: carboximethyl cellulose; cellulose; cellulose derivatives; hydrogels; hydroxypropylcellulose; methyl cellulose; scaffolds; stimuli responsive hydrogels; sustainable resources; tissue engineering.

Figure 1

Cellulose network structure.

Figure 2

Cellulose resources.

Figure 3

Bacterial cellulose production process.

Figure 4

Chemical structure of the most common cellulose derivatives.

Figure 5

Hydrogel physical and chemical crosslinking methods.

Figure 6

Freeze–thaw method consists of repeatedly freezing and thawing a polymer solution to induce phase separation and create porous structures.

Figure 7

Radical polymerization steps. A physical or chemical initiator agent induces the formation of free radicals. These radicals can bond with monomers, leading to the formation of chains of varying lengths. The termination step occurs when two free radicals link together through various mechanisms: (a) the merger of two free radicals, (b) the interaction of a radical with another free radical within a chain, and (c) the joining of two distinct chains, each containing a free radical.

Figure 8

Mixing HPC and PEG to create a chiral nematic hydrogel with unsaturated bonds causes polar responses to stimuli by changing its structure and, therefore, showing color transitions depending on the distance between its plates.

Figure 9

Cellulose-based hydrogels can be functionalized by copolymerization with other bio or synthetic polymers, the addition of growth factor or other biological material, and nanoparticles to fulfill tissue engineering requirements.

Figure 10

Cellulose-based hydrogels used for bioprinting human body tissue and evaluation of the printed scaffold by implantation in rats.

Figure 11

Cellulose-based injectable hydrogels loaded with growth factors, cells, drugs such as antibiotics or anti-inflammatory agents, and nanoparticles in a liquid state before physiological conditions and gel state after them.

Figure 12

Bacterial cellulose–graphene hydrogel for culture and growth of spiral ganglion neurons (SGNs) and development of growth cones (GC) and filopodia.