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

Tanase, Constantin Edi; Qutachi, Omar; White, Lisa J.; Shakesheff, Kevin M.; McCaskie, Andrew W; Best, Serena M; Cameron, Ruth E

Abstract

Tissue engineering response may be tailored via controlled, sustained release of active agents from protein loaded degradable microparticles incorporated directly within 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.

Citation

Tanase, C. E., Qutachi, O., White, L. J., Shakesheff, K. M., McCaskie, A. W., Best, S. M., & Cameron, R. E. (2019). Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds. Regenerative Biomaterials, 6(5), 279-287. https://doi.org/10.1093/rb/rbz015

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2019
• Online Publication Date: Apr 22, 2019
• Publication Date: 2019-10
• Deposit Date: May 28, 2019
• Publicly Available Date: May 30, 2019
• Journal: Regenerative Biomaterials
• Print ISSN: 2056-3418
• Electronic ISSN: 2056-3426
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 5
• Article Number: rbz015
• Pages: 279-287
• DOI: https://doi.org/10.1093/rb/rbz015
• Public URL: https://nottingham-repository.worktribe.com/output/2102563
• Publisher URL: https://academic.oup.com/rb/advance-article/doi/10.1093/rb/rbz015/5476185