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The choice of crosslinking chemistry for hydrogel development influences BMP-2 stability and bioactivity in vivo
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
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(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

Site-specific administration of bone morphogenetic protein-2 (BMP-2) at the site of a bone fracture via scaffolds can minimise systemic side-effects and exhibit sustained biological effects. While this method requires sufficient scaffolds to preserve the BMP-2 structure and tuned release patterns, the incorporation of thiol-acrylate chemistry has shown great success in scaffold synthesis. However, thiolates attack the sulphur atoms of disulphide bonds, displacing the other sulphur atom and forming a new disulphide bond, hence at physiological conditions, thiol-modified scaffold components could potentially attack inter-chain disulphide bonds of BMP-2 by thiol-exchange reactions. This therefore led us to compare hyaluronic acid (HA) hydrogels synthesised via thiol-acrylate (HA-S) and hydrazone crosslinking chemistry (HA-H) formed BMP-2 carriers. The study revealed the integrity of BMP-2 dimer structures can be disrupted and reveals the osteogenic capacity of BMP-2 by HA derivatives (HA-SH). BMP-2 bioactivity released from HA-S hydrogels are decreased when compared to HA-H hydrogels. This was further confirmed via the rat ectopic bone model, showing that bone volume was significantly higher when induced by HA-H hydrogels with BMP-2 than compared to HA-S hydrogel with BMP-2. This study gives new insights into scaffolds synthesis, showing that biomolecule bioactivity needs to be considered when choosing a chemistry for scaffolds synthesis. 

Keyword [en]
Hyaluronic acid, in vivo, bone morphogenetic protein, thiol-acrylate chemistry.
National Category
Medical Materials
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-307686OAI: oai:DiVA.org:uu-307686DiVA: diva2:1049878
Available from: 2016-11-25 Created: 2016-11-20 Last updated: 2016-11-27
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