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

Abstract

The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico-chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo-proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen-binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo-proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco-supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study.Similar protective perineural net structures assembled from the lectican proteoglycan family and HA also occur in the CNS/PNS. These so called perineuronal nets are visualized by immunolocalization of MAb 1B5 (+) epitope in rat brain (e) and pericellular 1B5(+) epitope expression by isolated neurons (f). Scale bars 100 µm.

The Glucosinolates: A Sulphur Glucoside Family of Mustard Anti-Tumour and Antimicrobial Phytochemicals of Potential Therapeutic Application

“…The effective delivery of SFN and AITCs to the target cells in solid tumours is a difficult proposition. Delivery systems based on hyaluronan as a carrier molecule have been developed for several steroids and cytotoxic compounds and successfully treated solid tumours however this methodology has yet to be applied to the delivery of SFN or AITCs in these problematic cancers (reviewed in [219]).…”

3D distribution of perlecan within intervertebral disc chondrons suggests novel regulatory roles for this multifunctional modular heparan sulphate proteoglycan

“…Perlecan is also involved in the co-acervation of tropoelastin, as part of the elastic microfibril assembly process at the cell surface in the AF (Hayes, 2011a). As stated, perlecan is a multifunctional PG and interacts with collagen types VI (Hayes et al, 2016) and type XI within the PCM compartment (Smith and to stabilise the chondron structure. It also interacts with a variety of structural and cell-adhesive glycoproteins at the cell surface and within the wider ECM (Gomes et al, 2004;Knox and Whitelock, 2006;Melrose et al, 2008a and b;Melrose et al, 2006).…”

Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues

“…Images a, c, d reproduced from [ 125 ] through Open Access. Image e modified [ 126 ] under Open Access.…”