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Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

Tutkimustuotosvertaisarvioitu

Standard

Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. / Yan, Hong Ji; Casalini, Tommaso; Hulsart-Billström, Gry; Wang, Shujiang; Podiyan Oommen, Oommen; Salvalaglio, Matteo; Larsson, Sune; Hilborn, Jöns; Varghese, Oommen P.

julkaisussa: Biomaterials, Vuosikerta 161, 03.02.2018, s. 190-202.

Tutkimustuotosvertaisarvioitu

Harvard

Yan, HJ, Casalini, T, Hulsart-Billström, G, Wang, S, Podiyan Oommen, O, Salvalaglio, M, Larsson, S, Hilborn, J & Varghese, OP 2018, 'Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation', Biomaterials, Vuosikerta. 161, Sivut 190-202. https://doi.org/10.1016/j.biomaterials.2018.01.041

APA

Yan, H. J., Casalini, T., Hulsart-Billström, G., Wang, S., Podiyan Oommen, O., Salvalaglio, M., ... Varghese, O. P. (2018). Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. Biomaterials, 161, 190-202. https://doi.org/10.1016/j.biomaterials.2018.01.041

Vancouver

Author

Yan, Hong Ji ; Casalini, Tommaso ; Hulsart-Billström, Gry ; Wang, Shujiang ; Podiyan Oommen, Oommen ; Salvalaglio, Matteo ; Larsson, Sune ; Hilborn, Jöns ; Varghese, Oommen P. / Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation. Julkaisussa: Biomaterials. 2018 ; Vuosikerta 161. Sivut 190-202.

Bibtex - Lataa

@article{d9101763c5b0428ba57aa4aee6e4b8c2,
title = "Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation",
abstract = "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.",
author = "Yan, {Hong Ji} and Tommaso Casalini and Gry Hulsart-Billstr{\"o}m and Shujiang Wang and {Podiyan Oommen}, Oommen and Matteo Salvalaglio and Sune Larsson and J{\"o}ns Hilborn and Varghese, {Oommen P.}",
year = "2018",
month = "2",
day = "3",
doi = "10.1016/j.biomaterials.2018.01.041",
language = "English",
volume = "161",
pages = "190--202",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

AU - Yan, Hong Ji

AU - Casalini, Tommaso

AU - Hulsart-Billström, Gry

AU - Wang, Shujiang

AU - Podiyan Oommen, Oommen

AU - Salvalaglio, Matteo

AU - Larsson, Sune

AU - Hilborn, Jöns

AU - Varghese, Oommen P.

PY - 2018/2/3

Y1 - 2018/2/3

N2 - 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.

AB - 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.

U2 - 10.1016/j.biomaterials.2018.01.041

DO - 10.1016/j.biomaterials.2018.01.041

M3 - Article

VL - 161

SP - 190

EP - 202

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -