Glycosaminoglycan and Proteoglycan‐Based Biomaterials: Current Trends and Future Perspectives

Abstract

Proteoglycans and their glycosaminoglycans (GAG) are essential for life as they are responsible for orchestrating many essential functions in development and tissue homeostasis, including biophysical properties and roles in cell signaling and extracellular matrix assembly. In an attempt to capture these biological functions, a range of biomaterials are designed to incorporate off-the-shelf GAGs, typically isolated from animal sources, for tissue engineering, drug delivery, and regenerative medicine applications. All GAGs, with the exception of hyaluronan, are present in the body covalently coupled to the protein core of proteoglycans, yet the incorporation of proteoglycans into biomaterials remains relatively unexplored. Proteoglycan-based biomaterials are more likely to recapitulate the unique, tissue-specific GAG profiles and native GAG presentation in human tissues. The protein core offers additional biological functionality, including cell, growth factor, and extracellular matrix binding domains, as well as sites for protein immobilization chemistries. Finally, proteoglycans can be recombinantly expressed in mammalian cells and thus offer genetic manipulation and metabolic engineering opportunities for control over the protein and GAG structures and functions. This Progress Report summarizes current developments in GAG-based biomaterials and presents emerging research and future opportunities for the development of biomaterials that incorporate GAGs presented in their native proteoglycan form.

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

“…Interesting recent developments in bioscaffold design have resulted in production of CS containing scaffolds with the ability to direct MSC cell differentiation in‐situ. in the context of tissue repair this can be used to promote the production of matrix components conducive to tissue repair . These bio‐scaffolds have yet to be applied to disc and annular repair, however they have properties which would be useful in such applications and are worthy of further examination.…”

“…in the context of tissue repair this can be used to promote the production of matrix components conducive to tissue repair. 127,128 These bio-scaffolds have yet to be applied to disc and annular repair, however they have properties which would be useful in such applications and are worthy of further examination.…”

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[47] A number of recombinant PGs have been successfully produced. [30,46] The stability of recombinant large PGs is also relevant to any prospective therapeutic application and it may be more expedient to use specific modules of the large PG in specific applications rather than the intact PG. Production of recombinant, large PGs such as aggrecan and perlecan have their own technical difficulties associated with their massive molecular dimensions and glycosylation characteristics.…”

“…[46,142] Reproducing GAG fine structures attached to recombinant core proteins to recapitulate native GAG structure is a challenging exercise. [46]); however, the GAG side chains of these recombinant proteins have not been a major focus in many of these studies and it is not clear to what extent the extensive GAG substitution of native aggrecan has been reproduced. In the case of aggrecan, its high degree of GAG substitution represents around 90% of its mass and is of functional importance in water imbibition, space-filling, and hydrodynamic properties which equip tissues with their unique weight bearing properties.…”

“…Vascular proteoglycan iii. 47,150. Treatment of vascular dementia v. Treatment of post-ischemic cerebral angiogenesis vi.…”