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Tuning biomaterial pH for regulating BMP-2 stability and bioactivity in vitro and 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]

The poor affinity of rhBMP-2 to the scaffolds leads to high dose administration requirement resulted in massive side effects has been the hurdle for successful clinic translation for treating delayed unions or remained non-union at bone defect. Optimizing the scaffolds with the purpose of obtaining optimal BMP2 dose and release have been addressed as critical for BMP-2 administration, however, the results are contradictory concerning whether bone formation is more beneficial from burst or controlled release of BMP2. While this might be due to these studies incorporated other bioactive molecules onto scaffolds to immobilize BMP-2.  In this study, we report the affinities of rhBMP-2 to the scaffolds can be improved by only tuning the pH of hyaluronic acid (HA) hydrazone crosslinking hydrogel without addition of other molecules. Neo bone induced by BMP-2 showed significantly higher volume with more impact structure and vascularization in pH 4.5 HA hydrogel compared to that in pH7 HA hydrogel. The mechanisms were demonstrated by In vitro BMP-2 release followed by diffusion quantitative calculation and computational simulation methods. Initial burst release of BMP-2 from pH 7 HA hydrogels with the fitting of Fickian behavior while sustained release from pH 4.5 HA hydrogel was observed. Computational stimulation revealed this is due to the protonation state of BMP2 at pH 4.5 resulted in stronger electrostatic interaction with negatively charged groups along the backbone of hyaluronic acid molecules compared to at pH 7. This study gives new direction to scaffolds designing for basic bioactive protein applications in future.  

Keyword [en]
RhBMP-2, Hyaluronic acid hydrogel, pH, in vivo bone formation.
National Category
Medical Materials
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-308444OAI: oai:DiVA.org:uu-308444DiVA: diva2:1049884
Available from: 2016-11-25 Created: 2016-11-25 Last updated: 2016-11-27
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