The cross-linking reaction of HA can be divided into complete or incomplete one. Besides, the mechanical strength of crosslinked HA can be remarkably improved compared to the non-crosslinked one, which makes it more suitable for tissue engineering applications. The purpose of HA cross-linking is to convert it from solid state to hydrogel state under mild conditions and to prolong its maintaining time in the human body. In this reaction, many different alcohols, such as fatty alcohols and aryl fatty alcohols can be bound to HA moleculesin order to improve the chemical properties of HA and its stability as a tissue engineering scaffold, as well as to extend its maintenance in the human body. Under certain conditions, the carboxyl group of HA can undergo esterification reaction to produce HYAFF, an esterified derivative of HA. The purpose of esterification is to link HA with certain hydrophobic groups, reducing the poly anion properties of HA. The chemical modification of HA can be roughly divided into two types: esterification and crosslinking. Many biomaterials do not have a lot of chemically modified sites, while HA can be chemically modified with its hydroxyl, carboxyl and N-acetylaminoends. To overcome this defect, chemical modification is indispensable. However, HA without modification tends to be absorbed rapidly in human body, which makes it unqualified in tissue engineering. The characteristics of HA including its consistency, biocompatibility, hydrophilicity, limited immunogenicity and unique viscoelasticity have made it an excellent moisturizer in cosmetic dermatology and skin-care products as well as a potential biomaterial in tissue engineering. However, it can also be degraded by reducing substances or at acidic pH values after modification. Under most circumstances, the HA macromere is degraded by hyaluronidase. In most instances, HA exhibited a highly porous morphology so that cells can permeate into the scaffold easily. Although higher molecular weight or crosslinking degree can result in improved compressive modulus that is essential in the tissue engineering of cartilage or bone, the viability of seed cells would be compromised. With macromereconcentrations from 2 to 20 wt%, networks exhibited volumetric swelling ratios ranging from ~42 to 8, compressive moduli ranging from ~2 to over 100 kPa, and degradation times ranging from less than 1 day up to almost 38 days in the presence of 100 U/mL of hyaluronidase. Moreover, the mutual macromolecular crowding in human body contributes to the higher viscosity. In human bodies, especially soft tissues, HA often exists in the form of high molecular weights which is the essential reason for its high viscosity even in diluted solutions. This phenomenon can be observed in HA solution as low as 1 mg/mL, which is one of the reasons to the unique rheological characteristics of HA. The molecular chains of HA are intertwined in solution and it occurs even when the concentration is very low. The high hydrophilicity of HA is the physical basis for its wide presence in the human body. HA has a molecular weight between 10 3 and 10 4 kDa, which can reach a length of 25 μm when fully extended. Skin and soft tissue engineering with HA-based scaffold were reviewed as well. The most important or typical papers discussing cartilage and bone tissue engineering using HA-based scaffolds were viewed and selectively cited. ![]() Therefore, to understand the application of HA, the basic physical, chemical and biological properties of HA must first be understood.Ī review of the literature was performed by searching the keywords “hyaluronic acid” AND “tissue engineering” OR “tissue regeneration” OR “stem cells” in PubMed, EMBASE and Medline. The versatility of HA is closely related to its unique properties, andHA with its different states or molecular weights can exhibitdiverse features. ![]() HA has become a hotspot in the fields of scaffold materials in tissue engineering because of its ubiquitously distribution in vertebrate tissues, good biocompatibility and non-toxic degradation products. Researches demonstrated that HA plays an important role in regulating cell differentiation, migration, angiogenesis and inflammation responses. HA is a linear polysaccharide without branches and is one of the most important components of extracellular matrix. It was named because of its transparent appearance in water and the probable presence of hexuronic acid as one of the components. Hyaluronic acid or hyaluronan (HA) was the first isolated from bovine vitreous humor by Meyer and Palmer in 1934.
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