Browsing by Author "Moldovan, Nicanor"

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    467 Enhancing Cell Infiltration and Controlled Growth Factor Release for a Customized 3D-Printed Bone Graft Composite
    (Cambridge University Press, 2024-04-03) Alston, Claudia Benito; Chadwick, Madelyn; Rupani, Saaniya; Moldovan, Nicanor; Barco, Clark; Solorio, Luis; Medicine, School of Medicine
    OBJECTIVES/GOALS: Annually, 1.5 million global patients receive maxillofacial reconstruction. The gold standard, involving bone particulate, lacks reproducibility. To improve this, we have developed a custom 3D-printable, porous cover-core design. This study optimizes the hydrogel core properties and growth factor (GF) release for enhanced bone regeneration. METHODS/STUDY POPULATION: Different ratios of Methacrylated Gelatin (GelMa), Methacrylated Alginate (AlgMa) and tricalcium phosphate (α²-TCP) were combined to optimize cell viability, GF sequestration and mechanical stability. Material characterization was performed using a rheometer to determine the viscoelastic properties of the blends. Release from disks loaded with FGF-containing PLGA microparticles was quantified with an ELISA kit. Furthermore, scanning electron microscopy (SEM) was conducted to quantify hydrogel porosity. In vitro studies were performed using NIH 3T3 murine fibroblasts in Corning Transwells while immunofluorescent, metabolic and osteogenic studies were performed in 96 well plates to investigate cell infiltration, cell adhesion, viability and differentiation, respectively. RESULTS/ANTICIPATED RESULTS: By adjusting the AlgGelMa ratio, we manipulated matrix properties. GelMa possesses excellent durability and cell adhesion due to intrinsic RGD-binding motifs. AlgMa enhanced swelling by 30%, growth factor sequestration by 50% in 24hrs, and matrix storage modulus without increasing the loss modulus which could cause cell migration away from the hydrogel. Varying the AlgGelMa ratio lowered pH, promoted cell infiltration, and reduced fibronectin accumulation. The addition of β-TCP is anticipated to improve cell differentiation towards an osteogenic lineage due to improved elastic modulus, calcium and phosphate ion concentration improving mineral deposition. DISCUSSION/SIGNIFICANCE: These findings suggest through the use of this composite, early cell infiltration can be increased and promoted due to FGF release, leading to increased osteointegration. Our porous cover-core design ensures efficient clot integration and early cell infiltration, enhancing osteointegration through FGF release.
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    Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis
    (Karger, 2021) Lagatuz, Mark; Vyas, Ruchi J.; Predovic, Marina; Lim, Shiyin; Jacobs, Nicole; Martinho, Miguel; Valizadegan, Hamed; Kao, David; Oza, Nikunj; Theriot, Corey A.; Zanello, Susana B.; Taibbi, Giovanni; Vizzeri, Gianmarco; Dupont, Mariana; Grant, Maria B.; Lindner, Daniel J.; Reinecker, Hans-Christian; Pinhas, Alexander; Chui, Toco Y.; Rosen, Richard B.; Moldovan, Nicanor; Vickerman, Mary B.; Radhakrishnan, Krishnan; Parsons-Wingerter, Patricia; Ophthalmology, School of Medicine
    The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.