Enhanced vascularity in gelatin scaffolds via copper-doped magnesium–calcium silicates incorporation: In-vitro and ex-ovo insights

Authors

• E. Salahinejad, Marquette University
• Avaneesh Muralidharan, Marquette University
• Forough Azam Sayahpour, Marquette University
• Maryam Kianpour, Marquette University
• Mohsen Akbarian, Marquette University
• Daryoosh Vashaee, North Carolina State University
• Lobat Tayebi, Marquette UniversityFollow

Document Type

Article

Publication Date

12-2025

Publisher

Elsevier

Source Publication

Ceramics International

Source ISSN

0272-8842

Abstract

Addressing a critical challenge in current tissue-engineering practices, this study aims to enhance vascularization in 3D porous scaffolds by incorporating bioceramics laden with pro-angiogenic ions. Specifically, freeze-dried gelatin-based scaffolds were infused with sol-gel-derived powders of Cu-doped akermanite (Ca₂MgSi2O₇) and bredigite (Ca₇MgSi₄O₁₆) at various concentrations (10, 20, and 30 wt%). The scaffolds were initially characterized for their structural integrity, biodegradability, swelling behavior, impact on physiological pH, and cytocompatibility with human umbilical vein endothelial cells (HUVECs). The silicate incorporation effectiveness in promoting vascularity was then assessed through HUVEC attachment, capillary tube formation, and ex-ovo chick embryo chorioallantoic membrane assays. The findings revealed significant improvements in both in-vitro and ex-ovo vascularity of the gelatin scaffolds upon the addition of Cu-doped akermanite. The most effective concentrations were determined to be 10 and 20 %, which led to notable HUVEC metabolic activity, a well-spread morphology with extensive peripheral filopodia and lamellipodia at 10 % and a cobblestone phenotype indicative of in-vivo endothelium at 20 % during cell attachment, the formation of complex networks of tubular structures, and robust vascularization in chick embryo development. Moving forward, the incorporation of Cu-doped akermanite into tissue-engineering scaffolds shows great potential for addressing the limitations of vascularization, especially for critical-sized bone defects, by facilitating the controlled release of pro-angiogenic and pro-osteogenic ions.

Comments

Accepted version. Ceramics International, Vol. 50, No. 20 (2025): 39889-39897. DOI. This article is © Elsevier. Used with permission.

Recommended Citation

Salahinejad, E.; Muralidharan, Avaneesh; Sayahpour, Forough Azam; Kianpour, Maryam; Akbarian, Mohsen; Vashaee, Daryoosh; and Tayebi, Lobat, "Enhanced vascularity in gelatin scaffolds via copper-doped magnesium–calcium silicates incorporation: In-vitro and ex-ovo insights" (2025). School of Dentistry Faculty Research and Publications. 590.
https://epublications.marquette.edu/dentistry_fac/590