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Synthetic design of...
Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
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- Yan, Hongji (författare)
- Uppsala universitet,KTH,Skolan för kemi, bioteknologi och hälsa (CBH),Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden,Polymerkemi
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- Casalini, Tommaso (författare)
- 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.
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- Hulsart Billström, Gry, 1982- (författare)
- Uppsala universitet,Ortopedi,Uppsala Univ, Dept Orthoped, Uppsala, Sweden.
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- Wang, Shujiang (författare)
- Uppsala universitet,Polymerkemi,Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
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- Varghese, Oommen P., 1977- (författare)
- Uppsala universitet,Polymerkemi,Translational Chemical Biology,Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
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- Salvalaglio, Matteo (författare)
- UCL, Thomas Young Ctr, London WC1E 7JE, England.;UCL, Dept Chem Engn, London WC1E 7JE, England.
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- Larsson, Sune (författare)
- Uppsala universitet,Ortopedi,Uppsala Univ, Dept Orthoped, Uppsala, Sweden.
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- Hilborn, Jöns, 1956- (författare)
- Uppsala universitet,Polymerkemi,Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
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- Varghese, Oommen P. (författare)
- Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
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- Oommen, Oommen P. (författare)
- Tampere Univ Technol, Bioengn & Nanomed Lab, Fac Biomed Sci & Engn, Tampere 33720, Finland.;Tampere Univ Technol, Biomeditech Inst, Tampere 33720, Finland.
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(creator_code:org_t)
- Elsevier, 2018
- 2018
- Engelska.
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 161, s. 190-202
- Relaterad länk:
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https://discovery.uc...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
- NATURVETENSKAP -- Kemi -- Polymerkemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Polymer Chemistry (hsv//eng)
Nyckelord
- Bone morphogenetic protein-2
- Hydrogels
- Hyaluronic acid
- Tissue engineering
- Biomedical applications
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- art (ämneskategori)
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Yan, Hongji
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Casalini, Tommas ...
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Hulsart Billströ ...
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Wang, Shujiang
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Varghese, Oommen ...
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Salvalaglio, Mat ...
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Larsson, Sune
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Hilborn, Jöns, 1 ...
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Varghese, Oommen ...
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Oommen, Oommen P ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Biomaterialveten ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Kemi
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och Polymerkemi
- Artiklar i publikationen
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Biomaterials
- Av lärosätet
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Kungliga Tekniska Högskolan
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Uppsala universitet