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Adv Mater. 2017 Sep;29(33). doi: 10.1002/adma.201701255. Epub 2017 Jul 4.

Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.

Author information

1
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53705, USA.
2
Comparative Orthopedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, 53705, USA.
3
Department of Biomedical Engineering, University of Wisconsin, Madison, WI, 53706, USA.
4
Department of Biology, University of Wisconsin, Madison, WI, 53705, USA.

Abstract

Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrate enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect is attributed to the maintenance of protein conformational structure, which is closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintains its biological activity for weeks during release, while it maintains activity for less than 7 d during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor using a mineral coated surgical suture significantly improves functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a two fold improvement in mechanical properties. The findings of this study demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine.

KEYWORDS:

mineral coating; nanostructures; protein delivery; protein stability; therapeutics

PMID:
28675637
PMCID:
PMC5628619
[Available on 2018-09-01]
DOI:
10.1002/adma.201701255

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