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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)
- Uppsala universitet,Polymerkemi,polymer chemistry
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Bowden, Tim (preses)
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Qian, Hong (preses)
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Griensven, Martijn van (opponent)
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(creator_code:org_t)
- ISBN 9789155497675
- Uppsala : Acta Universitatis Upsaliensis, 2016
- Engelska 87 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 1459
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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
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Medicinsk material- och protesteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Medical Materials (hsv//eng)
Nyckelord
- Chondroitin sulfate
- hyaluronic acid
- pH
- cross-linking chemistry
- bone morphogenetic protein
- lithium
- mesenchymal stem cell
- in vivo.
- Engineering Science with specialization in Nanotechnology and Functional Materials
- Teknisk fysik med inriktning mot nanoteknologi och funktionella material
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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