title: Hyaluronan: a simple polysaccharide with diverse biological functions.
abstract: Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of d-glucuronic acid and N-acetyl-d-glucosamine. It is evolutionarily conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways, which regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. This paper illustrates the properties of HA from a matrix biology perspective by first introducing the principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. It next highlights the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models.
authors.affiliation: Department of Materials Science and Engineering, 201 DuPont Hall, University of Delaware, Newark, DE 19716, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Dicker
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gurski
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; Helen F. Graham Cancer Center, Christiana Care Health Systems (CCHS), Newark, DE 19713, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Pradhan-Bhatt
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; Helen F. Graham Cancer Center, Christiana Care Health Systems (CCHS), Newark, DE 19713, USA; Otolaryngology - Head & Neck Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Witt
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77251, USA; Department of Bioengineering, Rice University, Houston, TX 77251, USA.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
authors.affiliation: Department of Materials Science and Engineering, 201 DuPont Hall, University of Delaware, Newark, DE 19716, USA; Biomedical Engineering Program, University of Delaware, Newark, DE 19716, USA; Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USA. Electronic address: xjia@udel.edu.
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
mesh_terms: D000818:Animals; D020811:Biomedical Technology; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009024:Morphogenesis; D009369:Neoplasms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014945:Wound Healing
chemical_list: D011506:Proteins; D006820:Hyaluronic Acid
keywords: Cancer; Hyaluronan; Morphogenesis; Tissue engineering; Wound healing