Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules

Abstract

Proteoglycans have emerged as biomacromolecules with important roles in matrix remodeling, homeostasis, and signaling in the past two decades. Due to their negatively charged glycosaminoglycan chains as well as distinct core protein structures, they interact with a variety of molecules, including matrix proteins, growth factors, cytokines and chemokines, pathogens, and enzymes. This led to the dawn of glycan therapies in the 20 th century, but this research was quickly overshadowed by readily available DNA and protein-based therapies. The recent development of recombinant technology and advances in our understanding of proteoglycan function have led to a resurgence of these molecules as potential therapeutics. This review focuses on the recent preclinical efforts that are bringing proteoglycan research and therapies back to the forefront. Examples of studies using proteoglycan cores and mimetics have also been included to give the readers a perspective on the wide-ranging and extensive applications of these versatile molecules. Collectively, these advances are opening new avenues for targeting diseases at a molecular level, and providing avenues for the development of new and exciting treatments in regenerative medicine.

Glycosaminoglycans in Tissue Engineering: A Review

“…DS has been implicated in the development of many pathologies, such as cancer metastasis [ 94 ], connective tissue diseases [ 95 ], and inhibited neuron regeneration [ 96 ]. Research focusing on DS in tissue engineering is sparse, with the bulk of research focusing on discovery of its functions and some research focusing on DS, modified DS, and DS proteoglycans as therapeutics or as a targeting mechanism for drug delivery [ 97 , 98 , 99 , 100 , 101 ]. This lack of exploration can likely be attributed to two key factors: the recent reclassification of DS from chondroitin sulfate B, and the extreme complexity of DS synthesis and physiological interactions.…”

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

“…Specific domains of proteoglycan core and/or HS chains as well as HSPG synthetizing and remodeling enzymes represent potential therapeutic targets [205]. Among the explored approaches, there is the use of high-affinity antibodies recognizing functional epitopes of HSPGs, HS mimetic compounds, cationic proteins which interact with the highly anionic sulfate and carboxylate moieties of HS chains, natural and synthetic peptides, small organic molecules that may affect either HSPG-protein interactions and subsequent signaling or the HSPG biosynthetic machinery [4][5][6]29,32,37,155,156,165,[239][240][241][242][243]. Some examples of HSPG targeting-based therapeutics for cancer treatment are reported in Table 4.…”

Sustained delivery of 17β-estradiol by human amniotic extracellular matrix (HAECM) scaffold integrated with PLGA microspheres for endometrium regeneration

“…Glycosaminoglycans (GAGs) are a class of long unbranched periodic negatively charged polysaccharides found in ECM that take part in many biological processes such as anticoagulation, angiogenesis and tissue regeneration (Walimbe & Panitch, 2019 ; Bojarski et al., 2020 ). They are partially responsible for the mechanical stability of tissues due to their capacity to retain a large quantity of water, enabling hydration of the ECM and rendering it resistant to compressive forces (Neves et al., 2020 ).…”