Moderate-Affinity Affibodies Modulate the Delivery and Bioactivity of Bone Morphogenetic Protein-2.


Journal

Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613

Informations de publication

Date de publication:
10 2023
Historique:
revised: 16 05 2023
received: 13 03 2023
pmc-release: 01 10 2024
medline: 23 10 2023
pubmed: 28 6 2023
entrez: 28 6 2023
Statut: ppublish

Résumé

Uncontrolled bone morphogenetic protein-2 (BMP-2) release can lead to off-target bone growth and other adverse events. To tackle this challenge, yeast surface display is used to identify unique BMP-2-specific protein binders known as affibodies that bind to BMP-2 with different affinities. Biolayer interferometry reveals an equilibrium dissociation constant of 10.7 nm for the interaction between BMP-2 and high-affinity affibody and 34.8 nm for the interaction between BMP-2 and the low-affinity affibody. The low-affinity affibody-BMP-2 interaction also exhibits an off-rate constant that is an order of magnitude higher. Computational modeling of affibody-BMP-2 binding predicts that the high- and low-affinity affibodies bind to two distinct sites on BMP-2 that function as different cell-receptor binding sites. BMP-2 binding to affibodies reduces expression of the osteogenic marker alkaline phosphatase (ALP) in C2C12 myoblasts. Affibody-conjugated polyethylene glycol-maleimide hydrogels increase uptake of BMP-2 compared to affibody-free hydrogels, and high-affinity hydrogels exhibit lower BMP-2 release into serum compared to low-affinity hydrogels and affibody-free hydrogels over four weeks. Loading BMP-2 into affibody-conjugated hydrogels prolongs ALP activity of C2C12 myoblasts compared to soluble BMP-2. This work demonstrates that affibodies with different affinities can modulate BMP-2 delivery and activity, creating a promising approach for controlling BMP-2 delivery in clinical applications.

Identifiants

pubmed: 37379021
doi: 10.1002/adhm.202300793
pmc: PMC10592408
mid: NIHMS1917936
doi:

Substances chimiques

Bone Morphogenetic Protein 2 0
Biocompatible Materials 0
Hydrogels 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2300793

Subventions

Organisme : NIBIB NIH HHS
ID : R21 EB032112
Pays : United States

Informations de copyright

© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

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Auteurs

Jonathan Dorogin (J)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.

Henry B Hochstatter (HB)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.
Department of Human Physiology, University of Oregon, 1320 E 15th Ave., Eugene, OR, 97403, USA.

Samantha O Shepherd (SO)

Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

Justin E Svendsen (JE)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.
Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

Morrhyssey A Benz (MA)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.
Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

Andrew C Powers (AC)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.

Karly M Fear (KM)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.

Jakob M Townsend (JM)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.

James S Prell (JS)

Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

Parisa Hosseinzadeh (P)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.
Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

Marian H Hettiaratchi (MH)

Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon, 6231 University of Oregon, Eugene, OR, 97403, USA.
Department of Chemistry and Biochemistry, University of Oregon, 1253 University of Oregon, Eugene, OR, 97403, USA.

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Classifications MeSH