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Engineering of BMP-silk for bone tissue applications
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
2018 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The biggest problem associated to bone-related diseases is the increased risk of bone fractures. It is estimated that 10-20% of all fractures do not self-heal and require some type of surgical intervention. Today’s current treatments to regenerate bone present several limitations. Autologous bone grafting, which is today’s golden standard works very well in regenerating osseous tissue, but the limited bone supply is a big problem. Clinically approved growth-factor based therapies, like the soluble rhBMP2, are very expensive and present several limitations, such as lack of control over its delivery, resulting in ectopic bone formation and other severe side-effects. This leaves us with an unmet demand for improved bone regenerative therapies. In this study we have looked into understanding the structure and function of bone to create a 2D spider silk-based cell scaffold for bone tissue engineering. Recombinant spider silk protein, 4RepCT was functionalized on genetic level with the osteoinductive peptide keBMP2, from which soluble keBMP2-4RepCT could be produced. The silk part retained its capacity to spontaneously self-assemble into silk-like fibers as well as surface coatings. A bioactive 2D scaffold with the capacity to induce osteoblastic differentiation of mouse mesenchymal stem cells (mMSCs) was produced by combining keBMP2-4RepCT with silk functionalized with fibronectin mimetic peptide (FN-4RepCT) with enhanced cell adhesive properties. The bioactivity of keBMP2 was confirmed by successful cultivation of mMSCs on the silk coatings and detection of elevated levels of the early osteogenic maker Alkaline Phosphatase (ALP). This study showed a sequential effect between keBMP2 and FN, indicating that keBMP2 can exert its osteoinductive potential in conditions that provide proper cell adhesion. This makes the combination of keBMP2-4RepCT and FN-4RepCT a good candidate to be used as a bone tissue engineering scaffold.

Place, publisher, year, edition, pages
2018.
National Category
Natural Sciences Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-239664OAI: oai:DiVA.org:kth-239664DiVA, id: diva2:1266796
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-29Bibliographically approved

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CiteExportLink to record
Permanent link

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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
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  • asciidoc
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