Sustained release of BMP-2 using self-assembled layer-by-layer film-coated implants enhances bone regeneration over burst release.

Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE

Publication: <1995-> : Amsterdam : Elsevier Science
Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980-

Bone Morphogenetic Protein 2*/pharmacology ; Bone Regeneration*; Animals ; Delayed-Action Preparations/pharmacology ; Osteogenesis ; Prostheses and Implants ; Rats

Current clinical products delivering the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) for bone regeneration have been plagued by safety concerns due to a high incidence of off-target effects resulting from bolus release and supraphysiological doses. Layer-by-layer (LbL) film deposition offers the opportunity to coat bone defect-relevant substrates with thin films containing proteins and other therapeutics; however, control of release kinetics is often hampered by interlayer diffusion of drugs throughout the film during assembly, which causes burst drug release. In this work, we present the design of different laponite clay diffusional barrier layer architectures in self-assembled LbL films to modulate the release kinetics of BMP-2 from the surface of a biodegradable implant. Release kinetics were tuned by incorporating laponite in different film arrangements and with varying deposition techniques to achieve release of BMP-2 over 2 days, 4 days, 14 days, and 30 days. Delivery of a low dose (0.5 μg) of BMP-2 over 2 days and 30 days using these LbL film architectures was then compared in an in vivo rat critical size calvarial defect model to determine the effect of BMP-2 release kinetics on bone regeneration. After 6 weeks, sustained release of BMP-2 over 30 days induced 3.7 times higher bone volume and 7.4 times higher bone mineral density as compared with 2-day release of BMP-2, which did not induce more bone growth than the uncoated scaffold control. These findings represent a crucial step in the understanding of how BMP-2 release kinetics influence treatment efficacy and underscore the necessity to optimize protein delivery methods in clinical formulations for bone regeneration. This work could be applied to the delivery of other therapeutic proteins for which careful tuning of the release rate is a key optimization parameter.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paula T Hammond reports a relationship with Moderna Therapeutics Inc that includes: board membership. Paula T Hammond reports a relationship with Performance Indicator that includes: board membership. Paula T Hammond reports a relationship with Alector Inc that includes: board membership. Paula T Hammond reports a relationship with LayerBio, Inc. that includes: board membership. Robert F Padera reports a relationship with Medtronic Inc that includes: consulting or advisory.
(Copyright © 2022. Published by Elsevier Ltd.)

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F30 DK130564 United States DK NIDDK NIH HHS; F32 DE027877 United States DE NIDCR NIH HHS; P30 CA014051 United States CA NCI NIH HHS; R01 DE024747 United States DE NIDCR NIH HHS

Keywords: BMP-2; Bone regeneration; Controlled release; Drug delivery; Layer-by-layer

0 (Bmp2 protein, rat)
0 (Bone Morphogenetic Protein 2)
0 (Delayed-Action Preparations)

Date Created: 20220818 Date Completed: 20220908 Latest Revision: 20230902

20230902

PMC10396073

10.1016/j.biomaterials.2022.121721

35981926