HA’s intrinsic physicochemical and biological properties suggest that this distinctive molecule is suitable for application in clinical therapies, diagnostics, tissue engineering scaffolds, and drug delivery devices. Unmodified, derivatized, and cross-linked HA have proven beneficial in a variety of applications, which are briefly described in the following sections.
Orthopedic Applications
HA plays a vital role in the development of cartilage, the maintenance of the synovial fluid, and the regeneration of tendons.High concentrations of HA can be found in the
ECM of all adult joint tissues, including the synovial fluid and the outer layer of cartilage. In part because of its viscoelastic nature and ability to form highly hydrated
matrices, HA acts in the joint as a lubricant and a shock absorber. In diseases such as osteoarthritis, the concentration and molecular weight of the HA naturally present in the joint are decreased, contributing to stiffness and pain. Viscosupplementation treatments aim to treat these conditions, and to this end, a variety of HA materials
have been successfully applied as clinical therapies.Researchers have also investigated cross-linked HA as cell delivery scaffolds for cartilage and bone tissue
engineering. Esterified HA (Hyaff, Fidia Advanced Biopolymers) supports the growth of chondrocytes and the differentiation of bone marrow–derived mesenchymal
progenitor cells into chondrocytes and osteoblasts. In fact, when compared to a well characterized delivery vehicle (porous calcium phosphate ceramic), Hyaff materials allowed greater amounts of bone and cartilage to be formed in vivo (as determined from the image analysis of stained tissue sections)
Antiadhesion Applications
As HA is highly hydrophilic, it is a polymer that is well suited for applications requiring minimal cellular adhesion. Postoperative adhesions, which form between adjacent tissue layers following surgery, impede wound healing and often require additional surgical procedures to repair successfully. Barriers made from cross-linked HA have been effectively used to prevent such adhesions from
forming. Furthermore, the adhesion of bacteria onto biomaterials can induce infections and great risk to the patient; with this in mind, esterified HA has also been
used to prevent bacterial adhesion to dental implants, intraocular lenses, and catheters.
Cardiovascular Applications
In a manner related to its antiadhesive properties, HA has also proven to be effective for increasing the blood compatibilities of cardiovascular implants such as vascular
grafts and stents. For example, biomaterial surfaces treated with cross-linked HA have been associated with reduced platelet adhesion and thrombus formation. Furthermore, sulfated HA derivatives can act as heparin mimics;] in fact, HA derivatives with higher degrees of sulfation are associated with increased abilities to prevent blood coagulation (as measured by longer times required for whole blood clotting).
Cross-linked HA is also a promising biomaterial for cardiac tissue engineering. In the embryo, HA is required for the normal development of the valves and chambers within the heart.Building upon this information, studies by Masters and Anseth have indicated that photopolymerized HA hydrogels are suitable materials for constructing tissue-engineered heart valves (K.S.Masters and K.S. Anseth, Department of Chemical Engineering,The University of Colorado at Boulder, 2003,personal communication). Valvular interstitial cells,which are the primary cell type found in heart valves,were found to adhere to and proliferate upon the HA hydrogels. Furthermore, the hyaladherins CD44 and RHAMM are present on the valvular interstitial cells,and these receptors were thought to be involved in promoting cellular proliferation in response to degraded HA hydrogel fragments.
Ophthalmology
HA, a natural component of the vitreous humor of the eye, has found many successful applications in ophthalmologic surgery. In part because it forms viscoelastic and highly hydrated matrices, HA is particularly useful as a spacefilling matrix in the eye; thus, intraocular injection of HA during surgery is used to maintain the shape of the anterior chamber. Furthermore, HA solutions also serve as a viscosity-enhancing component of eye drops and an adjuvant to eye tissue repair.
Dermatology and Wound-Healing Applications
HA is naturally present in high concentrations in the skin and soft connective tissues. Therefore, HA is an appropriate choice for a matrix to support dermal regeneration and augmentation. For example, Prestwich and coworkers found that cross-linked HA hydrogel films accelerate the healing of full-thickness wounds , presumably by providing a highly hydrated and nonimmunogenic environment that is conducive to tissue repair. Hyaff scaffolds cultured in vitro with keratinocytes and fibroblasts have been used to create materials similar to skin, including two distinct epidermal and
dermal-like tissue layers.Moreover, as a result of its ability to form hydrated, expanded matrices, HA has also been successfully used in cosmetic applications such as soft tissue augmentation.