Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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
  • text
  • asciidoc
  • rtf
Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
KTH. Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Chem & Bioengn, Vladimir Prelog Weg 1, CH-8093 Zurich, Switzerland.;Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Chem & Bioengn, Vladimir Prelog Weg 1, CH-8093 Zurich, Switzerland.;SUPSI, Dept Innovat Technol, Inst Mech Engn & Mat Technol, CH-6928 Manno, Switzerland..
Uppsala Univ, Dept Orthoped, Uppsala, Sweden..
Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden..ORCID iD: 0000-0003-3702-9459
Show others and affiliations
2018 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 161, p. 190-202Article in journal (Refereed) Published
Abstract [en]

Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 161, p. 190-202
Keywords [en]
Bone morphogenetic protein-2, Hydrogels, Hyaluronic acid, Tissue engineering, Biomedical applications
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:kth:diva-240150DOI: 10.1016/j.biomaterials.2018.01.041ISI: 000427100300017PubMedID: 29421555Scopus ID: 2-s2.0-85041442769OAI: oai:DiVA.org:kth-240150DiVA, id: diva2:1272436
Funder
Swedish Foundation for Strategic Research , 139400126, 139400127 139400127
Note

QC 20181219

Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Yan, Hong JiWang, ShujiangOommen, Oommen P.Varghese, Oommen P.
By organisation
KTH
In the same journal
Biomaterials
Biomaterials Science

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 32 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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
  • text
  • asciidoc
  • rtf