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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    
Yazarlar (15)
Emine Alarcin
Marmara Üniversitesi, Türkiye
Zeynep Puren Akguner
İstinye Üniversitesi, Türkiye
Ayca Bal Ozturk
İstinye Üniversitesi, Türkiye
Gokcen Yasayan
Yeditepe University, Turkey
Dr. Öğr. Üyesi Esra İLHAN AYIŞIĞI Dr. Öğr. Üyesi Esra İLHAN AYIŞIĞI
Kırşehir Ahi Evran Üniversitesi, Türkiye
Aslihan Kazan
Bursa Teknik Üniversitesi, Turkey
Ozlem Yesil-Celiktas
Ege University Faculty of Engineering, Turkey
Dila Sener Akcora
Marmara Üniversitesi Tip Fakültesi, Türkiye
Dilek Akakin
Marmara Üniversitesi Tip Fakültesi, Türkiye
Banu Kocaaga
İstanbul Teknik Üniversitesi, Turkey
Gamze Eren
Private Clinic, Turkey
Kasım Gunes
Marmara Üniversitesi Tip Fakültesi, Türkiye
Oya Kerimoglu
Marmara Üniversitesi, Türkiye
Hatice Kubra Seki
Yeditepe University, Turkey
F. Seniha Guner
İstanbul Teknik Üniversitesi, Turkey
Devamını Göster
Özet
The 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.
Anahtar Kelimeler
3D bioprinting | Bilayer scaffold | Bone regeneration | Bone scaffold | Controlled growth factor release | Vascularization
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı International Journal of Biological Macromolecules
Dergi ISSN 0141-8130 Wos Dergi Scopus Dergi
Dergi Grubu Q1
Makale Dili İngilizce
Basım Tarihi 05-2025
Cilt No 306
Sayı 1
Doi Numarası 10.1016/j.ijbiomac.2025.141440