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- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
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| 3. |
- Yan, Hongji, et al.
(författare)
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The choice of crosslinking chemistry for hydrogel development influences BMP-2 stability and bioactivity in vivo
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Annan publikation (populärvet., debatt m.m.)abstract
- 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.
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| 4. |
- Yan, Hongji, et al.
(författare)
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Tuning biomaterial pH for regulating BMP-2 stability and bioactivity in vitro and in vivo
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Annan publikation (populärvet., debatt m.m.)abstract
- 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.
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