Incorporation of heparin into biomaterials

Abstract

This review provides an overview on the incorporation of heparin into biomaterials with a focus on drug delivery and the use of heparin-based biomaterials for self-assembly of polymer networks. Heparin conjugation to biomaterials was originally explored to reduce the thrombogenicity of materials in contact with blood. Many of the conjugation strategies that were developed for these applications are still popular today for other applications. More recently heparin has been conjugated to biomaterials for drug delivery applications. Many of the delivery approaches have taken advantage of the ability of heparin to bind to a wide variety of growth factors, protect them from degradation and to potentiate their interactions with cell surface receptors. More recently, the use of heparin as a base polymer for scaffold fabrication has also been explored, often utilizing non-covalent binding of heparin with peptides or proteins to promote self-assembly of hydrogel networks. This review will highlight recent advances in each of these areas.

A review of bioactive plant polysaccharides: Biological activities, functionalization, and biomedical applications

“…Anticoagulant activity of the heparin highly relies on its specific structure sequence, within which the binding site of an important protein (antithrombin III) is crucial for heparin to prevent the generation of a fibrin clot which is formed by the action of thrombin (SchedinWeiss, Richard, Hjelm, & Olson, 2008). Understanding of this structure-activity relationship of heparin offers the opportunity to develop drugs with higher specificity and better regulation of coagulation and to explore other therapeutic applications such as infection, inflammation, cancer and wound-healing treatment (Linhardt, 2003;Rajangam et al, 2006;Sakiyama-Elbert, 2014;Zhang et al, 2013a;Zhang, Wardwell, & Bader, 2013b). CS/DS chains are composed variably sulfated N-acetylgalactosamine and glucuronic acid or its epimeride iduronic acid disaccharides repeating units (Silbert & Sugumaran, 2002;Takegawa et al, 2011).…”

“…HS chains are made up of variably sulfated and N-acetylated repeating disaccharide unites, i.e. glucuronic/iduronic acid and glucosamine (Chappell & Liu, 2013;Linhardt, 2003;Sakiyama-Elbert, 2014). Heparin, the most highly sulfacted heparan sulfate, has been widely used as the most effective clinical anticoagulant.…”

Quantification of aldehyde terminated heparin by SEC-MALLS–UV for the surface functionalization of polycaprolactone biomaterials

“…Although this is mentioned for the reader's consideration, the Schiff-base is regarded as stabile under ambient physiological conditions. Also, it should be noted that optimized heparin-aldehyde presented throughout this manuscript was only optimized with respect to oligomer synthesis and was not optimized with respect to antithrombin activity, surface concentration, or method of surface functionalization, although many efforts by others have focused on these important areas [58,59]. With the development of the previously described heparin-aldehyde quantitation assay, our future work will be focused on SEC-MALLS-UV based methods of characterizing heparin immobilized on PCL biomaterials, their mechanisms of binding, and residual amounts of aldehyde functional groups remaining.…”

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

“…As highly sulfated glycosaminoglycans, heparins bind growth factors through ionic reversible interactions. These systems mimic reservoirs of endogenous growth factors in extracellular matrix [14–19] in which secreted proteins are protected from denaturation and aggregation. Hydrogels functionalized with aptamers have been used to control protein release [20–23].…”