3D-porous β-tricalcium phosphate–alginate–gelatin scaffold with DMOG delivery promotes angiogenesis and bone formation in rat calvarial defects

  • Shahrbanoo Jahangir
  • Samaneh Hosseini
  • Farhad Mostafaei
  • Forough Azam Sayahpour
  • Mohamadreza Baghaban EslaminejadEmail author
Tissue Engineering Constructs and Cell Substrates Original Research
Part of the following topical collections:
  1. Tissue Engineering Constructs and Cell Substrates


Hypoxia-inducible factor-1α (HIF-1α), a well-studied angiogenesis pathway, plays an essential role in angiogenesis-osteogenesis coupling. Targeting the HIF-1a pathway frequently leads to successful reconstruction of large-sized bone defects through promotion of angiogenesis. Dimethyloxalylglycine (DMOG) small molecule regulates the stability of HIF-1α at normal oxygen tension by mimicking hypoxia, which subsequently accelerates angiogenesis. The current study aims to develop a novel construct by seeding adipose derived mesenchymal stem cells (ADMSCs) onto a scaffold that contains DMOG to induce angiogenesis and regeneration of a critical size calvarial defect in a rat model. The spongy scaffolds have been synthesized in the presence and absence of DMOG and analyzed in terms of morphology, porosity, pore size, mechanical properties and DMOG release profile. The effect of DMOG delivery on cellular behaviors of adhesion, viability, osteogenic differentiation, and angiogenesis were subsequently evaluated under in vitro conditions. Histological analysis of cell-scaffold constructs were also performed following transplantation into the calvarial defect. Physical characteristics of fabricated scaffolds confirmed higher mechanical strength and surface roughness of DMOG-loaded scaffolds. Scanning electron microscopy (SEM) images and MTT assay demonstrated the attachment and viability of ADMSCs in the presence of DMOG, respectively. Osteogenic activity of ADMSCs that included alkaline phosphatase (ALP) activity and calcium deposition significantly increased in the DMOG-loaded scaffold. Computed tomography (CT) imaging combined with histomorphometry and immunohistochemistry analysis showed enhanced bone formation and angiogenesis in the DMOG-loaded scaffolds. Therefore, spongy scaffolds that contained DMOG and had angiogenesis ability could be utilized to enhance bone regeneration of large-sized bone defects.



The present research was financially supported by Royan Institute for Stem Cell Biology and Technology. We thank Ms. Fatemeh Safari and Mr. Mohammad Hossein Ghanian for their help.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10856_2018_6202_MOESM1_ESM.docx (4.1 mb)
Supplementary information


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Stem Cells and Developmental Biology, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
  2. 2.Department of Tissue engineering & Regenerative Medicine, Faculty of Advanced Technologies in MedicineIran University of Medical SciencesTehranIran
  3. 3.Animal Core Facility, Reproductive Biomedicine Research CenterRoyan Institute for Biotechnology, ACECRTehranIran

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