Glycosylation as a design component of biomaterials in implant design.

Abstract

An implanted medical device is specified in detail through its bulk and surface chemistry, mechanical properties, architecture, degradation kinetics, and surface ligands, whereas the host receiving it is specified hardly at all. Much of what the host presents at that interface is glycan, and glycan-mediated recognition acts through defined receptor families, including the Siglecs, the C-type lectin receptors, the galectins, and the regulators of complement. The host glycome is not fixed. It is assembled combinatorially, varies with age, metabolic state, and inflammation, differs between recipients, and is altered systematically in disease. Those alterations are measurable before implantation and are resolved both regionally and temporally, N-glycosylation differing region by region within the human Parkinsonian nigrostriatum and α-2,6-sialylation rising from 19.5% of the N-glycan pool in healthy intervertebral disc to 23%-24% in degenerated tissue. This Perspective argues that glycosylation should be specified as a component of the biomaterials from which devices are built. Because a diseased glycome is typically altered in several respects at once, a design need not address all of it, and a single motif may be selected where it is quantitatively dominant, mechanistically implicated, and chemically tractable. Three propositions follow: host glycophenotype is a measurable covariate of outcome and a basis for patient stratification; glycan structure, sulfation, and presentation density are specifiable material properties, with sulfation tunable independently of backbone; the analytical methods required to control a glycan attribute are established, so that the obstacle is convention rather than capability.