Synthesis and characterization of an aggrecan mimic

Abstract

Aggrecan (AGG) is a large, aggregating proteoglycan present throughout the body, but predominantly found in articular cartilage. The principle features of AGG, its hyaluronan (HA) binding domain and its abundance of covalently attached glycosaminoglycans (GAGs), make it an essential component of the functional ability of articular cartilage. Current tissue engineering constructs have attempted to stimulate AGG production, but have been unable to produce adequate amounts of mature AGG, and hence have suffered a mismatch in mechanical properties. To address these deficiencies, an AGG mimic was synthesized to match AGG functional properties and provide greater control within tissue engineering constructs. Chondroitin sulfate was functionalized with HA-specific binding peptides to replicate both the GAG presence and HA-binding ability of AGG, respectively. Upon characterization and testing, the mimic was able to effectively bind to HA, increase the compressive strength of cartilage extracellular matrix-based constructs, and protect the other extracellular matrix (ECM) components from degradation, replicating the important functions of AGG. In particular, the mimic produced a 78% increase in compressive strength of the ECM-based constructs, and was able to significantly reduce the degradation of both HA and collagen. The initial characterization of the newly synthesized AGG mimic demonstrates its potential in tissue engineering constructs, and provides an essential basis for more explorative studies of the AGG mimic's abilities as an AGG substitute and beyond.