Bone regeneration in rat calvarial defects using dissociated or spheroid mesenchymal stromal cells in scaffold-hydrogel constructs

Stem Cell Research & Therapy

Mohamed Nageeb Hassan¹  Kamal Mustafa¹  Samih Mohamed-Ahmed¹  Salwa Suliman¹  Anne Isine Bolstad¹  Siddharth Shanbhag²  Stefan Tangl³  Toni Dobsak³  Patrick Heimel⁴  Carina Kampleitner⁴ 

[1] Center for Translational Oral Research (TOR), Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadveien 19, 5009, Bergen, Norway;Center for Translational Oral Research (TOR), Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Årstadveien 19, 5009, Bergen, Norway;Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway;Core Facility Hard Tissue and Biomaterial Research/Karl Donath Laboratory, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria;Austrian Cluster for Tissue Regeneration, Vienna, Austria;Core Facility Hard Tissue and Biomaterial Research/Karl Donath Laboratory, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria;Ludwig Boltzmann Institute for Traumatology, The research center in cooperation with AUVA, Vienna, Austria;Austrian Cluster for Tissue Regeneration, Vienna, Austria;

关键词: Xeno-free;    Platelet lysate;    MSC;    Spheroid culture;    Bone tissue engineering;   

DOI  :  10.1186/s13287-021-02642-w

来源: Springer

【 摘 要 】

BackgroundThree-dimensional (3D) spheroid culture can promote the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSC). 3D printing offers the possibility to produce customized scaffolds for complex bone defects. The aim of this study was to compare the potential of human BMSC cultured as 2D monolayers or 3D spheroids encapsulated in constructs of 3D-printed poly-L-lactide-co-trimethylene carbonate scaffolds and modified human platelet lysate hydrogels (PLATMC-HPLG) for bone regeneration.MethodsPLATMC-HPLG constructs with 2D or 3D BMSC were assessed for osteogenic differentiation based on gene expression and in vitro mineralization. Subsequently, PLATMC-HPLG constructs with 2D or 3D BMSC were implanted in rat calvarial defects for 12 weeks; cell-free constructs served as controls. Bone regeneration was assessed via in vivo computed tomography (CT), ex vivo micro-CT and histology.ResultsOsteogenic gene expression was significantly enhanced in 3D versus 2D BMSC prior to, but not after, encapsulation in PLATMC-HPLG constructs. A trend for greater in vitro mineralization was observed in constructs with 3D versus 2D BMSC (p > 0.05). In vivo CT revealed comparable bone formation after 4, 8 and 12 weeks in all groups. After 12 weeks, micro-CT revealed substantial regeneration in 2D BMSC (62.47 ± 19.46%), 3D BMSC (51.01 ± 24.43%) and cell-free PLATMC-HPLG constructs (43.20 ± 30.09%) (p > 0.05). A similar trend was observed in the histological analysis.ConclusionDespite a trend for superior in vitro mineralization, constructs with 3D and 2D BMSC performed similarly in vivo. Regardless of monolayer or spheroid cell culture, PLATMC-HPLG constructs represent promising scaffolds for bone tissue engineering applications.

【 授权许可】

CC BY