This review provides an overview of the latest applications of sulfonated molecules in biomaterials. Sulfonation, a chemical modification process introducing sulfonic acid groups, enhances biomaterial properties. This review explores the effect of sulfonation and recent innovations in biomaterial applications. It covers hydrogels, scaffolds, and nanoparticles, emphasizing sulfonation’s unique advantages. The impact on cellular responses, including adhesion, proliferation, and differentiation, is discussed. This review also addresses sulfonated biomaterials’ role in regenerative medicine, drug delivery, and tissue engineering challenges. It also provides a small overview of the sources and features of marine-derived sulfonated molecules, emphasizing their potential roles in advancing scientific research. As a novel aspect, an unconventional complex, “traditional Chinese medicine” and its sulfonation method have come to the forefront after a thousand years of history. This article concludes with a reflection on current research and future avenues, highlighting sulfonation’s transformative potential in biomedicine.

Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan (GAG) that is a versatile material whose biological, chemical, and physical characteristics can be deeply tuned to modifications. However, HA is easy to decompose by hyaluronidase in vivo, and this process will reduce its structure and function stability during application. The sulfonation of HA can improve its stability under the action of hyaluronidase. Sulfated hyaluronic acid (S-HA) can be synthesized by many methods, and it shows significantly slower degradation by hyaluronidase compared with HA. In addition, negatively charged S-HA has other advantages such as anti-adhesive activity, anti-inflammatory, macromolecules by electrostatic interactions, stable site absorption of positively charged molecules, and enhancement of growth factor binding ability. It has numerous applications in medical (anti-aging, inflammation, tissue regeneration, cancer therapy, wound healing, and drug delivery) and cosmetics as biomaterials and coatings. In this article, the advances of S-HA for potential application of biomaterials and biomedical coatings will be reviewed and comprehensively discussed.