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

Article; Early Access

关键词: POLY(ETHYLENE GLYCOL);    GROWTH-FACTOR;    CROSS-LINKING;    RECEPTOR COMPLEXES;    CONTROLLED-RELEASE;    HYDROGELS;    BMP-2;    KINETICS;    DEGRADATION;    MIMICKING;   

DOI  :  10.1002/adhm.202300793

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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