Collagen-Binding Peptidoglycans: A Biomimetic Approach to Modulate Collagen Fibrillogenesis for Tissue Engineering Applications

摘要

The small leucine-rich proteoglycans (SLRPs), prevalent in collagenous tissues, regulate collagen fibrillogenesis and provide a host of biochemical cues critical to tissue function and homeostasis. Incorporating SLRPs may enhance tissue engineering designs that mimic the native extracellular matrix, although SLRPs purified from animal sources bear low yields and lack design control. Consequently, we have designed synthetic peptidoglycans, inspired by the native SLRP decorin, that contain a collagen-binding peptide attached to a glycosaminoglycan (GAG) chain. These peptidoglycans modulate collagen fibrillogenesis and decrease fibril diameter in vitro, similarly to decorin, while maintaining the characteristic D-banded fibrils. Application for tissue engineering is demonstrated as these peptidoglycans are incorporated into collagen gels seeded with smooth muscle cells. Gels formed with peptidoglycans and decorin show a faster rate of gel compaction, and one peptidoglycan uniquely increases elastin production. The peptidoglycan design can be tailored with respect to the peptide sequence and GAG identity and is expected to have versatile application in tissue engineering.