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Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold

Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold
Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold
The combination of supportive biomaterials and bioactive factors to stimulate endogenous progenitor cells is of key interest for the treatment of conditions in which intrinsic bone healing capacities are compromised. To address this need a “scaffold-decoration platform” was developed in which a biocompatible, biotin-functionalised 3D structural polymer network was generated through a solvent blending process, and used to recruit avidin modified nanoparticles within its 3D structure through biotin-avidin conjugation. This was enabled via the generation of a suite of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, encapsulating two bioactive factors, vascular endothelial growth factor (VEGF) and L-Ascorbic acid 2-phosphate (AA2P) and conjugated to streptavidin to allow attachment to the bone generating scaffold. The levels of encapsulated and released VEGF and AA2P were tailored to fall within the desired range to promote biological activity as confirmed by an increase in endothelial cell tubule formation and collagen production by osteoblast cells in response to nanoparticle release of VEGF and AA2P, respectively. The release of VEGF from the scaffolds produced a significant effect on vasculature development within the chick chorioallantoic membrane (CAM) angiogenic assay. Similarly, the scaffolds showed strong biological effects in ex vivo assays indicating the potential of this platform for localised delivery of bioactive molecules with applications in both hard and soft tissue engineering.
2050-750X
4437-4445
Czekanska, Ewa
1e6bbcb7-5824-4b35-9ea6-7700c0ff51f4
Glinka, Michael
7630ab6c-91c5-4840-9c25-12cb61fcb91e
White, Kate
ad592ed1-c133-4e3a-abed-3803a6d5531c
Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Evans, Nicholas
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Bradley, Mark
562b9add-34c4-4620-bfa1-c7c83a0f0900
Czekanska, Ewa
1e6bbcb7-5824-4b35-9ea6-7700c0ff51f4
Glinka, Michael
7630ab6c-91c5-4840-9c25-12cb61fcb91e
White, Kate
ad592ed1-c133-4e3a-abed-3803a6d5531c
Kanczler, Janos
eb8db9ff-a038-475f-9030-48eef2b0559c
Evans, Nicholas
06a05c97-bfed-4abb-9244-34ec9f4b4b95
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Bradley, Mark
562b9add-34c4-4620-bfa1-c7c83a0f0900

Czekanska, Ewa, Glinka, Michael, White, Kate, Kanczler, Janos, Evans, Nicholas, Oreffo, Richard and Bradley, Mark (2018) Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold. Journal of Materials Chemistry B, (27), 4437-4445. (doi:10.1039/C8TB00474A).

Record type: Article

Abstract

The combination of supportive biomaterials and bioactive factors to stimulate endogenous progenitor cells is of key interest for the treatment of conditions in which intrinsic bone healing capacities are compromised. To address this need a “scaffold-decoration platform” was developed in which a biocompatible, biotin-functionalised 3D structural polymer network was generated through a solvent blending process, and used to recruit avidin modified nanoparticles within its 3D structure through biotin-avidin conjugation. This was enabled via the generation of a suite of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, encapsulating two bioactive factors, vascular endothelial growth factor (VEGF) and L-Ascorbic acid 2-phosphate (AA2P) and conjugated to streptavidin to allow attachment to the bone generating scaffold. The levels of encapsulated and released VEGF and AA2P were tailored to fall within the desired range to promote biological activity as confirmed by an increase in endothelial cell tubule formation and collagen production by osteoblast cells in response to nanoparticle release of VEGF and AA2P, respectively. The release of VEGF from the scaffolds produced a significant effect on vasculature development within the chick chorioallantoic membrane (CAM) angiogenic assay. Similarly, the scaffolds showed strong biological effects in ex vivo assays indicating the potential of this platform for localised delivery of bioactive molecules with applications in both hard and soft tissue engineering.

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Manuscript v06062018-1 - Accepted Manuscript
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Accepted/In Press date: 13 June 2018
e-pub ahead of print date: 14 June 2018

Identifiers

Local EPrints ID: 421721
URI: http://eprints.soton.ac.uk/id/eprint/421721
ISSN: 2050-750X
PURE UUID: e1e0c942-d3c0-4de3-9059-2c3822e068b9
ORCID for Janos Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 25 Jun 2018 16:30
Last modified: 22 Nov 2021 06:28

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Contributors

Author: Ewa Czekanska
Author: Michael Glinka
Author: Kate White
Author: Janos Kanczler ORCID iD
Author: Nicholas Evans
Author: Richard Oreffo ORCID iD
Author: Mark Bradley

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