The use of hydrogels in tissue engineering

Researchers working in the tissue engineering field are constantly looking for new biomimetic materials to enhance the regeneration of damaged or lost tissues and organs. Hydrogels are three-dimensional network structures constituted of hydrophilic polymers cross-linked either by chemical covalent bonds or physical interactions. These materials are very mimetic to the cell microenvironment therefore, they have been widely used in tissue engineering, providing mechanical support for cells. In addition, hydrogels have excellent biocompatibility, causing minimal inflammatory responses, thrombosis, and tissue damage. Several types of hydrogels with different structures, compositions, and properties have been developed in recent years. 1 2

Hydrogels have high water content and can swell large amounts of water without polymer dissolution due to their hydrophilic and crosslinked structure, giving them physical characteristics that mimic native tissues, particularly soft tissues. Furthermore, these biomaterials have high permeability to oxygen, nutrients, and other water-soluble metabolites. 1 2

A variety of synthetic and natural polymers can be used to form hydrogels for tissue engineering scaffolds. Synthetic materials include poly (ethylene oxide), poly (vinyl alcohol), poly (acrylic acid), and polypeptides. Natural polymers include agarose, alginate, chitosan, collagen, fibrin, gelatin, and hyaluronic acid. Hydrogels can be prepared by various methods depending on the designed structure and the intended application, which include the polymerization or crosslinking of hydrogel precursors through chemical or physical approaches. 3

Researchers are striving to design hydrogels with modified physical and chemical properties to better respond to external stimuli such as temperature, pH, light, enzymes, magnetic and electrical fields. This type of hydrogel is called “smart hydrogel” and has shown great potential in regenerative medicine therapies, tissue engineering, and artificial organ implantation. 1

Figure 1: The most common classes of hydrogels. 3

A study by Park et al. (2014) examined the proliferation, differentiation, and migration of chondrocytes and osteoblasts in hyaluronic acid (HA) and type I collagen (Col-1) hydrogels seeking to develop an approach for osteochondral regeneration. The team demonstrated that chondrocytes exhibited better cell proliferation and function than chondrocytes in Col-1 hydrogels and osteoblasts in HA hydrogels. Finally, 3D osteochondral tissue mimetic structures composed of two compartments, osteoblast-encapsulated Col-1 hydrogels, and chondrocyte-encapsulated HA hydrogels were bioprinted; and it was observed that the viability and functions of each cell type were well maintained within the 3D structures up to 14 days in vitro. 4

Hydrogels are also widely used in skin regeneration therapies and chronic diabetic wounds. For this purpose, Wang et al. (2019) developed an antibacterial hydrogel (PHE@exo) based on polypeptides (Pluronic F127, oxidative hyaluronic acid, and Poly-ε-L-lysine) with stimuli-responsive exosomes from adipose-derived mesenchymal stem cells. In vitro, the hydrogel promoted human umbilical vein endothelial cells’ proliferation, migration, and tube-forming capacity. In vivo, the hydrogel was able to increase the healing efficiency of full-thickness diabetic skin wounds significantly. In addition, in vivo analysis was characterized by increased wound closure rates, rapid angiogenesis, re-epithelialization, and collagen deposition at the wound site in rats. 5

Figure 2: Images of the healing process in wounds treated with FHE, exosomes, FHE@exo, and control. 5


1. Mantha, S. et al. Smart Hydrogels in Tissue Engineering and Regenerative Medicine. Materials 12, (2019).

2. Nguyen, K. T. & West, J. L. Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23, 4307–4314 (2002).

3. El-Sherbiny, I. M. & Yacoub, M. H. Hydrogel scaffolds for tissue engineering: Progress and challenges. Glob Cardiol Sci Pract 2013, 316–342 (2013).

4. Park, J. Y. et al. A comparative study on collagen type I and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting. Biofabrication 6, 035004 (2014).

5. Wang, C. et al. Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration. Theranostics 9, 65–76 (2019).