2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 5th, 2025
Version: 1
University of Oregon
bioengineering
biorxiv

Phased affinity-controlled delivery of vascular endothelial growth factor, fibroblast growth factor-2, and platelet derived growth factor enhances in vitro angiogenesis

Svendsen, J. E.Open in Google Scholar•Asnes, C. L.Open in Google Scholar•Nightheart, S. R.Open in Google Scholar•Ford, M. R.Open in Google Scholar•Hajarizadeh, A.Open in Google Scholar•Oh, S. C.Open in Google Scholar•Hochstatter, H. B.Open in Google Scholar•O'Hara-Smith, J. R.Open in Google Scholar•Guldberg, R. E.Open in Google Scholar•Hettiaratchi, M. H.Open in Google Scholar

Angiogenesis, the growth of vasculature from existing blood vessels, requires the coordinated secretion of multiple angiogenic growth factors that each stimulate the cellular recruitment, patterning, and morphogenesis inherent to vascular network formation. Among these secreted factors, vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and platelet derived growth factor (PDGF) amplify key stages of angiogenesis. Disruptions in their secretion have been implicated in poor vascular network formation. Current methods for exploring variations in the phased presentation of multiple different proteins are limited, which has restricted our ability to explore the effect of growth factor timing on angiogenesis. To address this knowledge gap, we developed affibodies, which are alpha-helical binding proteins, to phase the release of VEGF-165, FGF-2, and PDGF-BB from a single drug delivery vehicle via specific protein-affibody affinity interactions. We used yeast surface display to engineer three VEGF-, three FGF-2-, and two PDGF-specific affibodies with different affinities for their target proteins. We demonstrated that the cumulative release of VEGF and FGF-2 are inversely correlated with the strength of the protein-affibody affinity interaction and that hydrogels containing multiple protein-specific affibodies can independently control the release of VEGF, FGF-2, and PDGF, largely in accordance with the strength of the affinity interactions. Using a rat-derived intact microvascular fragment model of in vitro angiogenesis, we revealed that sequential delivery of soluble VEGF, followed by FGF-2, and then PDGF enhances vascular network formation and branching. We then designed an affibody-conjugated hydrogel to mimic this sequence of protein delivery, resulting in increased vascular branching and network length compared to all other hydrogel compositions and the sequential delivery of soluble growth factors. This work establishes a new platform for modulating the timing of growth factor delivery, enabling the exploration of how temporal variations in protein secretion impact regeneration and development.

Similar Papers

biorxiv
Sat Jul 05 2025
A Compact Two-Photon Module for Simultaneous Dual-Depth, Multi-Region in vivo Brain Imaging
Understanding how distributed brain regions interact across cortical depths is crucial for uncovering the neural basis of behavior and cognition. Two-photon microscopy (2PM) excels at imaging the superficial layer, while three-photon microscopy (3PM) penetrates deep tissues but lacks sufficient speed for capturing fast superficial dynamics. Here, we present a compact two-photon imaging module (2PI...
Zhao, Y.
•
Gu, X.
•
Kong, C.
•
Liu, S.
...•
Li, B.
biorxiv
Sat Jul 05 2025
Ambient Proteins: Training Diffusion Models on Low Quality Structures
We present Ambient Protein Diffusion, a framework for training protein diffusion models that generates structures with unprecedented diversity and quality. State-of- the-art generative models are trained on computationally derived structures from AlphaFold2 (AF), as experimentally determined structures are relatively scarce. The resulting models are therefore limited by the quality of synthetic da...
Daras, G.
•
Ouyang-Zhang, J.
•
Ravishankar, K.
•
Daspit, W.
...•
Diaz, D. J.
biorxiv
Sat Jul 05 2025
A combined Eulerian-Lagrangian and thin film approximation model to investigate the disease-specific drug delivery efficacy on realistic lung geometry and breathing profiles
This study presents a computational assessment of antiviral liquid particle deposition in realistic human respiratory airways, comparing the actual inhalation cycle of a chronic obstructive pulmonary disease (COPD) patient to an ideal and healthy subject. Antiviral drugs are inhaled as fine droplets or mist, forming a thin liquid film along the airway walls of critical areas where respiratory viru...
Verma, S. K.
•
Bhardwaj, S.
•
Patel, K. S.
•
Naik, B. K.
biorxiv
Sat Jul 05 2025
Long-acting hydrogel-based depot formulations of tirzepatide and semaglutide for the management of type 2 diabetes and weight
Several incretin hormone therapies have been clinically approved and have revolutionized the treatment of diabetes and obesity. Promising therapeutics include semaglutide (Ozempic and Wegovy), an agonist for glucagon-like peptide-1 (GLP-1) receptor, and tirzepatide (Mounjaro), a dual agonist for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. These molecules help to regulat...
d'Aquino, A. I.
•
Dong, C.
•
Nguyen, L. T.
•
Yan, J.
...•
Appel, E. A.
biorxiv
Sat Jul 05 2025
Volumetric Bioprinting of Bone-like Mineralizing Hydrogel Constructs in the Presence of High Cell Densities and Mineral Precursors
A major challenge in bone tissue engineering is the embedding of osteocyte-like cells at high density within a mineralized matrix at the micro-scale and a trabecular-like architecture at the macro-scale. Volumetric bioprinting (VBP) enables rapid creation of complex cell-laden constructs through tomographic light projections. However, integrating both high cell densities and inorganic mineral prec...
de Wildt, B. W. M.
•
Bernero, M.
•
Zauchner, D.
•
Mueller, R.
•
Qin, X.-H.
biorxiv
Sat Jul 05 2025
Optical Coherence Tomography with Fluorescein Optical Clearing for Transscleral Image Guidance
Optical coherence tomography (OCT) is a non-invasive, three-dimensional imaging modality demonstrated to yield a wealth of high-resolution structural and functional information in a variety of biomedical imaging applications. However, there is a significant limitation on the penetration depth of the modality in most tissues due to their high optical scattering, hindering imaging of more deeply emb...
Trout, R. M.
•
Narawane, A.
•
Viehland, C.
•
Ownagh, V.
...•
Toth, C.
biorxiv
Sat Jul 05 2025
Synergistic Antimicrobial Activity of Epinecidin-1 and Its Variants with Antibiotics Against Nosocomial Pathogens: Implications for In Vivo Wound Healing
In this study, we investigated the antimicrobial properties of the antimicrobial peptide (AMP) epinecidin-1 and its variants against a range of nosocomial bacterial pathogens. The bacteriostatic effects on Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Staphylococcus aureus were evalu-ated using the microbroth dilution techniq...
Jeyarajan, S.
•
Kumarasamy, A.
biorxiv
Sat Jul 05 2025
Scale-Specific Viscoelastic Characterization of Hydrogels: Integrated AFM and Finite Element Modeling
Viscoelastic hydrogels mimic the dynamic mechanical properties of native extracellular matrices, making them essential for biomedical applications. However, characterizing their scale-dependent mechanical properties remains challenging, despite their critical influence on cell-material interactions and biomaterial performance. Here, we present an integrated experimental-computational approach to q...
Fertala, N.
•
Uhlmann, K.
•
Grigoryev, E.
•
Seth, P.
...•
Balzani, D.
biorxiv
Sat Jul 05 2025
Focal neurostimulation of propagating calcium waves in human neural cells using megahertz-range single-pulse focused ultrasound
Focused ultrasound (FUS) offers a promising neurostimulation technique that addresses the trade-off between invasiveness and spatial selectivity found in conventional electromagnetic-based methods. Evidence supporting its theoretical selectivity and comprehensive descriptions of the underlying biophysical mechanisms remain insufficient to ensure adequate control and safety. Based on observations o...
Aubier, T.
•
Suarez-Castellanos, I. M.
•
Perier, M.
•
Huberfeld, G.
...•
N'Djin, W. A.