Application and potential of hyaluronic acid in tissue engineering

Tissue engineering is a comprehensive discipline that combines engineering and natural science. It uses the biologically active substance to replace or repair organs and tissues through in vitro culture or construction. This concept was proposed by the National Science Foundation of the United States in 1987 and has developed rapidly in the following two decades [1]. The three elements of tissue engineering: cells, scaffold, and growth factor, have been able to regenerate bone, cartilage, skin, kidney, liver, digestive tract, cornea, muscle, breast, and other tissues and organs.

One of the main approaches in tissue engineering is to deliver cells, and bioactive substitutes (e.g., growth factors) to patients using 3D scaffolds (Fig. 1). The cells and growth factors are selected according to the type of tissue to be repaired, and the scaffolds act as temporary artificial extracellular matrices (ECM) that house the cells and direct their growth in three dimensions to form new tissue. ?Polymers are ideal as scaffold materials for tissue engineering because they can be tailored to have desired properties (e.g., mechanical features, geometric shapes, biocompatibility, minimal toxicity) and be degraded at the same rate as new tissue formed.

Hyaluronic acid (sodium hyaluronate, HA) is a glycosaminoglycan found in the extracellular matrix of most connective tissues. This component can naturally participate in tissue repair and exhibits unique viscoelasticity, biodegradability, biocompatibility, etc., making it an ideal material for tissue engineering. However, due to the low turnover rate and limited mechanical properties of native HA solutions, it is necessary to use different linkers to cross-linking natural HA to better fulfill the tissue engineering mission.

HA tissue engineering scaffolds can be prepared in the form of hydrogels, sponges, cryogels, etc. [2] HA hydrogels can mimic human tissue in terms of water content and exchange oxygen, nutrients, and metabolic waste, which are the ideal materials for 3D printing [3]. The HA sponges are characterized by their high porosity, allowing cell encapsulation and proliferation. Studies on wound healing and angiogenesis in wounds show the incorporation of different nanoparticles (NPs) in the chitosan–HA sponges for an enhanced effect [4]. Cryogels have been studied chiefly for their applications in cartilage tissue engineering as a substitute for extracellular matrix.?

HA-based tissue engineering applications have been extensively studied, and breakthroughs have been made in the regeneration of tissues such as cartilage, bone, skin, nerve, and heart (Fig. 2).

Reference：

[1]?Langer, R & Vacanti JP, Tissue engineering. Science 260, 920-6; 1993.

[2]?Chircov C, Grumezescu A M, Bejenaru L E . Hyaluronic acid-based scaffolds for tissue engineering[J]. Romanian journal of morphology and embryology, 2018, 59(1):71-76.

[3]?Zhu Z, Wang YM, Yang J, Luo XS. Hyaluronic acid: a versatile biomaterial in tissue engineering. Plast Aesthet Res, 2017, 4:219–227.

[4]?Chircov C , Grumezescu A M , Bejenaru L E . Hyaluronic acid-based scaffolds for tissue engineering[J]. Romanian journal of morphology and embryology, 2018, 59(1):71-76.