Hyaluronic Acid

Hyaluronic acid, or hyaluronan, is a water soluble, anionic extracellular matrix glycosaminoglycan polymer with variable molecular weight that determines its physiological role, rheological properties and applications. Since its discovery in the early 1930s, there has been an increased awareness concerning the biology of hyaluronic acid, its signaling pathways and its role in the biomedical and cosmeceutical industry. Being an endogenous molecule, hyaluronic acid is biocompatible, biodegradable, and has strong mucoadhesive, viscoelastic properties. The authors provide chemical modification approaches to hyaluronic acid, as well as address the magnitude of applications of hyaluronic acid-based targeted drug vectors and patents. The closing study discusses glycosaminoglycans, a specialized group of unbranched, anionic disaccharide polymers attached by a covalent linkage to the membrane proteins via sulphate groups in their sugar moieties.

Hyaluronic acid (HA) is found in extracellular tissue in many parts of the body. It is a material of increasing importance to biomaterials science and is finding applications in diverse areas ranging from tissue culture scaffolds to cosmetic materials. Its properties, both physical and biochemical, in solution or hydrogel form, are extremely attractive for various technologies concerned with body repair. This book considers the materials science behind some of the important biomedical and therapeutic applications that are emerging for HA. Key characteristics such as its mechanical properties, biological function and degradation are discussed. The latest technologies in chemical modification and crosslinking strategies are analysed and emerging applications in soft and hard tissue repair are highlighted. The first objective of the book, which consists of a collection of chapters from leading researchers across the globe, is to highlight the role of HA based hydrogels as scaffolds in sustaining stem cells for transplantation and regrowth. The second objective is to detail the significant influence of HA derived materials in the latest advances in cancer therapy, general therapeutics and cosmetics. The third objective is to link the structure-property relationships of HA to medical function and application while reflecting on current clinical and market trends. The book will be of interest to those involved in HA research for medical device and therapeutic applications. Graduate and undergraduate students engaged in the fields of biomedical engineering, materials science, chemistry, medical science, pharmaceutical science and polymer science will find this book of particular interest.

The biological outcome of Hyaluronan (also hyaluronic acid, abbreviated HA) interaction with its CD44 or RHAMM receptors recently attracted much attention within the scientific community owing to a Nature article by Tian X et al. (Nature 2013; 499:346-9). The article described a life span exceeding 30 years in naked mole rats, whereas the maximal lifespan of mice, to which the naked mole rat is related, is only 4 years. This observation is accompanied by the finding that the naked mole rat, in contrast to the mouse, does not develop spontaneous tumors during this exceptional longevity. The article provides evidence that interaction of long tissue HA (6000-12,000 kDa) of the naked mole rat with cell surface CD44, in contrast to the interaction of short tissue HA (less than 3000 kDa) with the mouse CD44, makes the difference. More specifically, this communication shows that the interaction of short HA with fibroblasts’ CD44 imposes on them susceptibility for malignant transformation, whereas the corresponding interaction with long HA imposes on the fibroblasts a resistance to malignant transformation. The article does not explain the mechanism that underlines these findings. However, the articles, that will be published in the proposed Research Topic in the Inflammation section of Frontiers in Immunology, can bridge not only this gap, but also may explain why interaction between short HA and cell surface CD44 (or RHAMM, an additional HA receptor) enhances the development of inflammatory and malignant diseases. Furthermore, the articles included in the proposed Frontiers Research Topic will show that cancer cells and inflammatory cells share several properties related to the interaction between short HA and cell surface CD44 and/or RHAMM. These shared properties include: 1. Support of cell migration, which allows tumor metastasis and accumulation of inflammatory cells at the inflammation site; 2. Delivery of intracellular signaling, which leads to cell survival of either cancer cells or inflammatory cells; 3. Delivery of intracellular signaling, which activates cell replication and population expansion of either cancer cells or inflammatory cells; and 4. Binding of growth factors to cell surface CD44 of cancer cells or inflammatory cells (i.e., the growth factors) and their presentation to cells with cognate receptors (endothelial cells, fibroblasts), leading to pro-malignant or pro-inflammatory activities. Going back to the naked mole rat story, we may conclude from the proposed articles of this Frontiers Research Topic that the long HA, which displays anti-malignant effect, interferes with the above described pro-malignant potential of the short HA (perhaps by competing on the same CD44 receptor). Extrapolating this concept to Inflammation, the same mechanism (competition?) may be valid for inflammatory (and autoimmune) activities. If this is the case, long HA may be used for therapy of both malignant and inflammatory diseases. Moreover, targeting the interaction between short HA and CD44 (e.g. by anti-CD44 blocking antibodies) may display also a therapeutic effect on both malignant and inflammatory diseases, an issue that encourages not only fruitful exchange of views, but also practical experimental collaboration.

Hyaluronic acid is an essential part of connective, epithelial and neural tissues, and contributes to cell proliferation and migration. It is used as a stimulating agent for collagen synthesis and is a common ingredient in skin-care products, a multi-billion dollar industry, as it is believed to be a key factor in fighting the aging process. Hyaluronic Acid: Production, Properties, Application in Biology and Medicine consists of six chapters discussing the various issues of hyaluronic acid research. In Chapter 1, a historical analysis recounts the discovery and milestones of the research leading to the practical applications of hyaluronan. Chapter 2 is dedicated to biological role of the hyaluronic acid in nature, in particular in the human body. The chapter starts from the phylogenesis of hyaluronic acid, then describes hyaluronan functions in human ontogenesis and especially the role which hyaluronan plays in extracellular matrix of the different tissues. Chapter 3 describes the methods to manufacture and purify hyaluronic acid, including the analytical means for assessing quality of the finished product. Chapter 4 discusses the structure and rheological properties of hyaluronic acid considering effects on conformation and biological properties related to molecular weight. In Chapter 5, the physical and chemical methods for modifying the structure of hyaluronan are discussed including cross-linking using bi-functional reagents, solid-phase modification and effects of the combined action of high pressures and shift deformation. The final chapter focuses on the products derived from hyaluronic acid, including therapeutics composed of modified hyaluronan conjugated to vitamins, amino acids and oligo-peptides. The biological roles and medical applications of this polysaccharide have been extensively studied and this book provides a wealth of scientific data demonstrating the critical role of hyaluronic acid and its promise as a multifaceted bio-macromolecule. Approaching hyaluronic acid from multiple angles, this book links relationships between its biological functions, structure and physical–chemical properties. It will be an invaluable resource to researchers, both industrial and academic, involved in all aspects of hyaluronan-based technologies.

The aging process affects every aspect of the body, with the face being one of the first places to show signs. The search for the perfect injectable filler has taken an interesting path with the majority of innovations having been introduced in the last 30 years. The patient-driven demand for safe and effective minimally invasive aesthetic procedures has led to the development of an expanding and competitive market for dermal fillers. The demand for soft tissue augmentation has grown rapidly since its start in 1981 with collagen fillers. Fillers using hyaluronic acid, calcium hydroxyapatite, poly-L-lactic acid, and polymethylmethacrylate provide a wide range of options so that the best cosmetic outcome can be attained. The ability to correct facial rhytides and folds, to augment lips and cheeks, to correct acne scars, and now even to replenish volume loss in the dorsum of the hands is something that many practitioners thought would never be possible. This publication reviews the history of fillers, injection techniques, complications and safety as well as the novel use of fillers and fillers of the future.

"Hyaluronic acid, or hyaluronan, is a water soluble, anionic extracellular matrix glycosaminoglycan polymer with variable molecular weight that determines its physiological role, rheological properties and applications. Since its discovery in the early 1930s, there has been an increased awareness concerning the biology of hyaluronic acid, its signaling pathways and its role in the biomedical and cosmeceutical industry. Being an endogenous molecule, hyaluronic acid is biocompatible, biodegradable, and has strong mucoadhesive, viscoelastic properties. The authors provide chemical modification approaches to hyaluronic acid, as well as address the magnitude of applications of hyaluronic acid-based targeted drug vectors and patents. The closing study discusses glycosaminoglycans, a specialized group of unbranched, anionic disaccharide polymers attached by a covalent linkage to the membrane proteins via sulphate groups in their sugar moieties"--