UTILITY AND CONTROL OF PROTEOGLYCANS IN TISSUE ENGINEERING

Proteoglycans (PGs) and their glycosaminoglycan (GAG) have been used commonly in tissue engineering (TE) to produce scaffolds. However, their specific biophysical and biological functions in TE have not been fully studied. Proteinglycan is an important part of the extracellular matrix (ECM). PG molecule consists of a core protein and the GAG chains. The core protein doesn’t have serine residues. GAG chains are attached to core protein by tetrasaccharide link. The variety of PGs are the result of the variety of GAG chains attach to core protein. GAGs are long chains of disaccharide units that are sulfated differently. PGs in the native tissues have roles in tissue remodeling, intracellular signaling, cell migration, cell compressibility and transparency, and other functions. PGs in the extracellular space are the following: basement membrane PGs, hyalectines, and small leucine-rich PGs (SLRPs). In this paper, we will discuss the functions of perlycan in the TE scaffold. Another category of PGs is the cell surgace PGs, which include syndecans, glypicans. Thrombomodulin, and CD44. The more we learn about functions of specific PG and its GAGs, the closer we are to reconstruct native environment of tissues.
This paper review two kinds of PGs and GAGs grafted in scaffolds. The first one is collagen-GAG scaffold. The collagen-GAG suspension is solidified, which results in the co-precipitation of collagen-GAG and the growing ice crystals. The GAG chains are then grafted to the scaffold through exposure to high temperature. This process also sterilizes the scaffold. Studies have proved that the present of GAGs in scaffold improve tissue growth and regeneration over the use of collagen alone. This type of scaffold help inducing cells to retain more PG aggregates in scaffold and retain more newly synthesized PGs within the cell layers. Collagen-GAG scaffolds recently have been used in nerve regeneration, artificial skin, osteogenic and chondrogenic tissue development. Studies have suggested that osteoblasts seeded in collagen-GAG scaffolds show greater adhesion, proliferation and make more markers. Silicone tube-collagen-GAG combination has shown more success in inducing greater number of axons per nerve. There are also many applications of this type of scaffold discussed in this paper.
Matrigel scaffolds have also been studied for TE applications. Matrigel is a soluble extract of Engelbreth-Holm-Swarm tumor cells’ basement membrane. Its components include laminin, fibril, nidogen, entactin, collagen IV, perlecan, and growth factors. This scaffold has been used to study tumor cell migration and invasion of the basement membrane. HSPG perlycan is one of the major component of matrigel which has not been studied widely. It is suggested to play key roles in blood vessel growth. The C-terminus of perlycan has been reported to inhibit endothelial cell migration, collagen-induced endothelial tube formation, and blood vessel growth in vivo. Therefore, it is suggested to contribute in the control of tumor cell growth.
There are still many type of PGs and GAG that are commonly used in TE. Scientists have done many studies on the total amount of PGs synthesized in engineered tissues. However, not many studies have been done to fully explore the potentials of PGs in creating the native environment of tissues.