Repository logo
 

Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds.

Accepted version
Peer-reviewed

Loading...
Thumbnail Image

Type

Article

Change log

Authors

Tanase, Constantin Edi  ORCID logo  https://orcid.org/0000-0003-1624-4790
Qutachi, Omar 
White, Lisa J 
Shakesheff, Kevin M 
McCaskie, Andrew W 

Abstract

Tissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen.

Description

Keywords

EDC crosslinking, FITC-BSA, PLGA microparticles, collagen scaffolds, percolation diameter, pore size

Journal Title

Regen Biomater

Conference Name

Journal ISSN

2056-3418
2056-3426

Volume Title

6

Publisher

Oxford University Press (OUP)
Sponsorship
European Research Council (320598)
Medical Research Council (MR/L022893/1)
Medical Research Council (MC_PC_12009)
This work was supported by the European Research Council [ERC Advanced Grant 320598 3D-E] and was also funded by a grant from the Medical Research Council, Arthritis Research UK, Reumafonds and the UKRMP