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New insights into p...
New insights into principles of scaffolds design for bone application
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Yan, Hongji 1986- (författare)
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Bowden, Tim (preses)
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Qian, Hong (preses)
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visa fler...
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Griensven, Martijn van (opponent)
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visa färre...
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(utgivare)
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(medarbetare)
- Uppsala Acta Universitatis Upsaliensis 2016
- Engelska 87
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1651-6214
Abstract
Ämnesord
Stäng
- This thesis presents deeper insights into bone applicable biomaterials’ design. Poor affinity of BMP-2 towards scaffolds required supra- physiological dose administration. Though molecules containing sulfate could sustain BMP-2 release, side effects occurred due to BMP-2 supra -dose, or these sulfate-containing biomolecules. Improved affinity between BMP-2 and scaffolds was first witnessed by using an acidic carrier ( paper I) . Hyaluronic acid (HA) hydrazone derived hydrogels having a pH of 4.5-loaded BMP-2 showed sustained release of bioactive BMP-2 in vitro and enhanced bone formation in vivo , while pH 7 HA hydrogels showed Fickian behavior and less bone formation in vivo . Computational evaluation revealed stronger electrostatic interactions between BMP-2, and HA were predominant at pH 4.5, whereas, weaker Van der Waals interactions played a key role at pH 7. During the pre-bone formation phase, endogenous cell responses to pH 4.5 and 7 with or without BMP-2 were investigated. HA hydrogels exhibited extraordinary biocompatibility and recruitment of neutrophils, monocytes, macrophages and stromal cells regardless of hydrogels’ pH and BMP-2 presence. The different inflammatory responses to HA hydrogels were observed ( Appendix ). Thiol derivatives can cleave the disulfide bond of BMP-2 to generate inactive monomeric BMP-2. In paper II, thiol-acrylate chemistry-based HA hydrogels (HA-SH) were compared to hydrazone-based HA hydrogels as BMP-2 carriers. Thiol modified HA disrupted BMP-2 integrity and bioactivity. HA-SH hydrogels with BMP-2 exhibited less bioactive BMP-2 release in vitro and induced less bone formation in vivo . Accumulated evidence has shown great osteogenic potential of lithium ions (Li). In paper III, we coordinated Li onto HA-PVA hydrazone hydrogels (Li-gel); Li-gel enhanced 3D cultured hMSCs osteogenic differentiation and induced higher bone formation in CAM defect model. Instead of BMP-2 protein, delivery of BMP-2-coding-plasmid can produce BMP-2 over a long term at a closer physiological level. Yet, efficient gene delivery reagents are needed. In paper IV , two novel gene delivery nanoplexes were developed by post coating DNA-nanoplexes with chondroitin sulfate (CS). To ensure the stability, aldehyde-modified CS (CS-CHO) reacted with free amines of pDNA/PEI complexes. We provided first evidence that CS-CHO coated nanoplexes controlled the release from endosomes, which is essential for higher transfection efficiency.
Ämnesord
- Engineering and Technology (hsv)
- Medical Engineering (hsv)
- Medical Materials (hsv)
- Teknik och teknologier (hsv)
- Medicinteknik (hsv)
- Medicinska material och protesteknik (hsv)
- Engineering Science with specialization in Nanotechnology and Functional Materials (uu)
- Teknisk fysik med inriktning mot nanoteknologi och funktionella material (uu)
Nyckelord
- Chondroitin sulfate
- hyaluronic acid
- pH
- cross-linking chemistry
- bone morphogenetic protein
- lithium
- mesenchymal stem cell
- in vivo.