Utility and control of proteoglycans in tissue engineering.

This review addresses various methods of integrating proteoglycans (PGs) into the design of engineered tissues and provides insight for designing tissue-engineered disease models that leverage current knowledge of PG biology. Even though PGs show immense possibilities in tissue-engineering applications, they have seldom been used to their full potential. The most common tissue-engineering application of PGs has been in scaffolds (matrigels and collagen-chondroitin sulfate matrices), in which PGs or their glycosaminoglycan (GAG) chains are incorporated into the scaffold to promote cell growth, tissue remodeling, and intracellular signaling. In addition, many studies have reported the total amount of PGs synthesized within engineered tissues but have not delineated which specific PGs or GAG classes are involved in engineered tissue development. In native tissues, various PGs are dynamically and differentially regulated to achieve specific biophysical and biological functions, such as compressibility and transparency. Therefore, the targeted modulation of specific PGs (via exogenous addition, endogenous stimulation with growth factors, or mechanical stimulation) may help engineered tissues to achieve native tissue properties. The PG composition of engineered tissues could also be modified to achieve disease models in vitro and thus provide a way to study the effect of external agents on PG-related disease mechanisms.