In Search of Bioactivities of Hyaluronan and Its Fragments: A Mini-review

Hyaluronic acid (HA) is a biopolymer widely distributed in the extracellular matrix, synovial fluid, and other tissues, where it plays a key role in hydration, cell signaling, and wound healing. High-molecular-weight HA (HMWHA) is primarily produced through microbial fermentation, while enzymatic degradation has become the preferred method for obtaining low-molecular-weight HA (LMWHA) due to its high purity and scalability. The biological functions of HA are strongly influenced by its molecular weight. HMWHA remains localized due to limited permeability, whereas LMWHA, particularly HA35, penetrates tissues more effectively, interacts with receptors and ion channels, and exhibits potent anti-inflammatory and analgesic properties. The presence of high levels of HA in the naked mole rat has been linked to its advantages in cancer resistance, longevity, and reduced pain sensitivity, significantly expanding its clinical applications. Furthermore, the development of high-dose oral HA therapies has opened new avenues for clinical use. As research continues, the therapeutic potential of LMWHA is expected to become increasingly prominent, reinforcing its role in modern medicine and biotechnology. This review provides a comprehensive overview of HA’s historical development, molecular characteristics, and recent scientific and industrial advancements, highlighting its expanding contributions to biomedical innovation.