Biomimetic 3D bioprinted bilayer GelMA scaffolds for the delivery of BMP-2 and VEGF exogenous growth factors to promote vascularized bone regeneration in a calvarial defect model in vivo

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dc.authorid0000-0001-9496-7324
dc.authorid0000-0003-0170-2269
dc.authorid0000-0002-5299-2924
dc.contributor.authorAlarcin, Emine
dc.contributor.authorAkguner, Zeynep Puren
dc.contributor.authorOzturk, Ayca Bal
dc.contributor.authorYasayan, Gokcen
dc.contributor.authorIlhan-Ayisigi, Esra
dc.contributor.authorKazan, Aslihan
dc.contributor.authorGuner, F. Seniha
dc.date.accessioned2026-02-08T15:15:18Z
dc.date.available2026-02-08T15:15:18Z
dc.date.issued2025
dc.departmentBursa Teknik Üniversitesi
dc.description.abstractThe effective treatment of critical-sized bone defects requires a coordinated interaction between osteogenesis and angiogenesis. Inspired by natural bone tissue, we developed a bilayer vascularized bone construct using extrusion-based dual 3D bioprinting. The construct consists of two layers: a bone-mimetic layer, which includes highly methacrylated gelatin (GelMAHIGH), hyaluronic acid, alginate, osteoblast cells, and bone morphogenetic protein-2 (BMP-2) loaded polylactic-co-glycolic acid (PLGA) nanoparticles; and a vessel-mimetic layer, composed of low methacrylated gelatin (GelMALOW), alginate, endothelial cells, and vascular endothelial growth factor (VEGF)-loaded PLGA nanoparticles. These layers were designed to form hierarchical microstructures that enable sustained release of growth factor (GF) thereby stimulating both osteogenic and angiogenic processes. The nanoparticles were synthesized using a microfluidic platform, achieving a narrow size distribution. The hydrogel bioinks were systematically optimized for printability, and it was found that incorporation of nanoparticles improved their mechanical properties, surface roughness, degradability, and GF release profiles. Notably, GF release followed zero-order kinetics, ensuring consistent delivery over time. The bilayer scaffolds demonstrated superior cell proliferation and spreading compared to single-layer scaffolds, and in vivo experiments showed enhanced repair of calvarial bone defects. These findings highlight the significant clinical potential of bilayer scaffolds with sequential GF delivery for treating critical-sized bone defects.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK) [217S365]
dc.description.sponsorshipThis study was funded by the Scientific and Technological Research Council of Turkiye (TUBITAK) (Grant Number 217S365) .
dc.identifier.doi10.1016/j.ijbiomac.2025.141440
dc.identifier.issn0141-8130
dc.identifier.issn1879-0003
dc.identifier.pmid40015394
dc.identifier.scopus2-s2.0-105000752598
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ijbiomac.2025.141440
dc.identifier.urihttps://hdl.handle.net/20.500.12885/5689
dc.identifier.volume306
dc.identifier.wosWOS:001459204900001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofInternational Journal of Biological Macromolecules
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzWOS_KA_20260207
dc.subjectControlled growth factor release
dc.subject3D bioprinting
dc.subjectBone scaffold
dc.subjectBilayer scaffold
dc.subjectVascularization
dc.subjectBone regeneration
dc.titleBiomimetic 3D bioprinted bilayer GelMA scaffolds for the delivery of BMP-2 and VEGF exogenous growth factors to promote vascularized bone regeneration in a calvarial defect model in vivo
dc.typeArticle

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