Bespoke 3D-Printed Polydrug Implants Created via Microstructural Control of Oligomers

Ruiz-Cantu, Laura; Trindade, Gustavo F.; Taresco, Vincenzo; Zhou, Zuoxin; He, Yinfeng; Burroughs, Laurence; Clark, Elizabeth A.; Rose, Felicity R.A.J.; Tuck, Christopher; Hague, Richard; Roberts, Clive J.; Alexander, Morgan; Irvine, Derek J.; Wildman, Ricky D.

Abstract

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up"without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Citation

Ruiz-Cantu, L., Trindade, G. F., Taresco, V., Zhou, Z., He, Y., Burroughs, L., Clark, E. A., Rose, F. R., Tuck, C., Hague, R., Roberts, C. J., Alexander, M., Irvine, D. J., & Wildman, R. D. (2021). Bespoke 3D-Printed Polydrug Implants Created via Microstructural Control of Oligomers. ACS Applied Materials and Interfaces, 13(33), 38969-38978. https://doi.org/10.1021/acsami.1c07850

• Journal Article Type: Article
• Acceptance Date: Jul 9, 2021
• Online Publication Date: Aug 16, 2021
• Publication Date: Aug 25, 2021
• Deposit Date: Jul 13, 2021
• Publicly Available Date: Aug 17, 2022
• Journal: ACS Applied Materials & Interfaces
• Print ISSN: 1944-8244
• Electronic ISSN: 1944-8252
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 33
• Pages: 38969-38978
• DOI: https://doi.org/10.1021/acsami.1c07850
• Keywords: 3D printing; drug release; implants; phase separation; inks
• Public URL: https://nottingham-repository.worktribe.com/output/5781920
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsami.1c07850