Moderate-Affinity Affibodies Modulate the Delivery and Bioactivity of Bone Morphogenetic Protein-2.
affibodies
bone morphogenetic protein-2
controlled protein delivery
hydrogels
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
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
e2300793Subventions
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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