Regenerative potential of glycosaminoglycans for skin and bone

Abstract

To meet the growing need for tissue replacement materials for our aging population, the development of new adaptive biomaterials is essential. The tissues with the highest demand for implant materials are skin and bone. These tissues share various similarities, including signaling pathways and extracellular matrix composition. Glycosaminoglycans such as hyaluronan and chondroitin sulfate are the major organic extracellular matrix components. They modulate the attraction of skin and bone precursor cells and their subsequent differentiation and gene expression and regulate the action of proteins essential to bone and skin regeneration. The precise action of glycosaminoglycans varies according to their structural composition mainly in respect to the degree of sulfation and polymer length. Changes in the glycosaminoglycan composition are frequently seen in physiological and pathological remodeling processes, such as bone formation or scaring. Here, we review the current state of knowledge of how the most common glycosaminoglycan, chondroitin sulfate and hyaluronan, interact with bone and skin cells, and summarize their potential in tissue engineering for skeletal and skin diseases.

Osteoblast-released Matrix Vesicles, Regulation of Activity and Composition by Sulfated and Non-sulfated Glycosaminoglycans

“…The use of sulfated GAGs could be a promising approach in bone grafting because in vitro studies showed promoting effects on osteogenesis (3,14). However, besides stimulating bone formation and reducing bone resorption, the alteration of GAG concentrations has also been reported to correlate with cancer progression by activating oncogenic pathways (92), promoting invasion and metastasis (93), and accelerating shedding of extracellular vesicles (94,95), which have to be carefully evaluated prior to clinical application.…”

“…Their sequence varies with respect to saccharide composition, glycosidic bond, and modification of the disaccharide unit, e.g. the degree of sulfation (3). GAGs modulate water and extracellular cation homeostasis.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…Negatively charged GAGs mediate and regulate various functions, mainly by electrostatic interactions with proteins in the ECM. Hence, they are a promising tool to increase the biocompatibility of biomaterials (Salbach et al, 2012). The structures of GAGs differ in their saccharide composition, glycosidic linkage and their chemical modification such as sulfation (Figure 3).…”

“…These events can lead to the so-called foreign body reaction, which can eventually cause loosening of the implant, inflammation, coagulation or, in a secondary event, infections ( Figure 1A) (Anderson et al, 2008;Trindade et al, 2016). To circumvent these issues, biomaterials are coated with components of the extracellular matrix (ECM) such as proteins, specific peptide sequences or glycosaminoglycans (GAGs) (Geissler et al, 2000;LeBaron and Athanasiou, 2000;Lee et al, 2011b;Salbach et al, 2012;Chlupac et al, 2014;Agarwal et al, 2015). However, to address additional biological cues or to increase specificity and activity, multifunctional coatings are required ( Figure 1B).…”

Review of Major Theories of Skin Aging

“…The precise action of glycosaminoglycans varies according to their structural composition mainly in respect to the degree of sulfation and polymer length. Changes in the glycosaminoglycan composition are frequently seen in physiological and pathological remodeling processes, such as bone formation or scaring [119].…”