Regenerative medicine and tissue engineering were considered as alternative treatments for organ transplant during the previous three decades. Organ failure and loss of tissue were challenging situations as the demand for organs is high, very few donors would be available and due to necessity for taking medication all through the life. The engineering and life science principles that help in improving biological substitutes to maintain and develop tissue function constitute tissue engineering (TE). The main intention behind TE is to the provide growth factors or cells to the patients through 3D scaffolds. The growth factors and the cells are selected depending on the nature of tissue to be repaired and the provided scaffolds work as extracellular matrix that help the growth of cells in 3 dimensions to form a novel tissue.

Polymers are considered as ideal substances to function as scaffold materials for tissue engineering. The polymers are either represented by artificial or natural molecules. The synthetic polymers like poly-N-iso propylacrylamide, polyvinyl alcohol and polyethylene glycol are investigated to study the slight modifications they undergo to attain some physical and mechanical properties. The hydrogel scaffolds are generated by using natural polymers like fibrin, collagen type-I, chondroitin sulfate, Chitosan and hyaluronic acid. The polymers derived from hydrogel are biodegradable and are similar to extracellular matrix. Collagen hydrogels are found to be immunogenic and fibrin hydrogels result in fibrin peptide aggregates that are insoluble.

Hyaluronic acid

HA is glycosaminoglycan polysaccharide which does not consist of protein backbone and is useful as good material for tissue engineering. The purified HA is known to be present in various molecular weights. Due to the short rate of turnover and very few mechanical features of natural HA, the chemical modifications of HA are essential for obtaining stable bio-materials. The current review paper focuses on the applications and products of HA for diagnosis and treatment.

HA hydrogels

Hydrogels are utilized in TE as they possess properties like porosity, bio-compatibility and hydrophilic character. The HA hydrogels are created by covalent cross linking or they are derived due to the hydrophobic groups added to HA. The chemical modification of HA has to be carried out in mild pH and temperature conditions allowing the functionalization and maintainance of the native properties of HA. The HA chemical modification is obtained by modifying the carboxylic acid group of glucuronic acid molecule or hydroxyl groups present in the two sugar rings.

Hydrogel preparation

HA gels are manufactured by the covalent cross linking of components of native HA like bisepoxides, formaldehyde, divinylsulfone, biscarbodiimides and dihydrazides along with EDC (1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. EDC is found to react with hydroxyl groups of HA. Cross linking of functional HA was utilized effectively for HA hydrogel preparation which is helpful in the In-Vivo gel formation. The homo-bifunctional cross linkers were studied by using diacrylated PEG and thiolated HA along with methacrylated HA combined with dithiothreitol.

Tissue Engineering

If the tissue is damaged extensively, then tissue transplantation or prosthetic implant are observed and practiced as a medical solution. These therapeutic options do have certain limitations and risks. Tissue engineering is observed as an alternative to tissue transplantation and prosthetic implantation. Tissue engineering could exhibit positive consequences exclusively for acute and small lesions. Tissue engineering has extensive clinical applications if used in chronic lesions.

TE accelerates the procedure of formation of tissue by distributing stem cells and growth factors In Situ with the help of bio-material scaffolds like HA centered scaffolds that are degradable. Bone tissue engineering constitutes injectable polymer dependent scaffolds of HA hydrogels and osteo stem cells, which were generated and differentiated in bone building cells accompanied by growth factors like bone morphogenic proteins and proteins related to TGF-beta family. The HA centered polymers are used for carrying the cells for the repair of cartilage and bone tissues.

The tissue engineering method which is minimally invasive is called as Hyalograft constituting the implantation of chondrocytes grown on 3D hyaluronan based scaffold. Hyalograft is considered as rapid, easy and safer method, is also considered as a possible treatment option for treating acute lesions in the cartilage.

HA dependent scaffolds used for drug delivery

The hydrogels made of HA are utilized for transdermal and dermal drug delivery systems. These systems are made specially to have the ability to regulate the drug release through the skin into the systemic blood circulation. This way of drug delivery is known to enhance the efficacy of the drugs and decrease the dosage and adverse effects of them. Releasing DNA into the body through hydrogel scaffolds would enhance the application of gene therapy in the regeneration of tissues. A process called caged nano particle encapsulation was done to gather unaggregated non-viral gene delivery nano particles and push them into HA hydrogels.

HA scaffold usage in anti-aging

HA centered scaffolds symbolize the injectable dermal fillers used for esthetic, anti-aging purposes and used as specialists of plastic surgery. HA has many applications in wound healing, skin regeneration and wrinkle treatment. In these procedures, it helps in the correction of the defects in the soft tissue. HA material has tremendous capacity to bind water and get implanted easily and hence is considered as an effective, non-surgical and non-invasive method for rectifying the facial defects.


Farid Menaa, Abder Menaa, and Bouzid Menaa. Hyaluronic Acid and Derivatives for Tissue Engineering. J Biotechnol Biomaterial, 2011, S1.

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