Endothelial and Osteoblast Differentiation of Adipose-Derived Mesenchymal Stem Cells Using a Cobalt-Doped CaP/Silk Fibroin Scaffold

Abstract

A major problem in the treatment of large bone defects is the inability to provide an adequate blood supply to the implantation site. Therefore, a bone regeneration strategy that provides an adequate supply of vessels would address this need. Cobalt (Co2+), because of its ability to induce hypoxia, has been used to accelerate new vessel formation. In this study, we used a freeze-drying technique to fabricate a scaffold that consisted of Co2+-doped calcium phosphate (CaP) [e.g., hydroxyapatite (HA)] and natural silk fiber through an optimized alternate mineralization process. The composition and structure of the scaffold were confirmed by X-ray diffraction (XRD), Fourier transform infrared (FTIR), inductively coupled plasma (ICP), and scanning electron microscope (SEM). The data showed that the scaffolds promoted differentiation of adipose-derived mesenchymal stem cells (ADSCs) toward endothelial and osteoblast linages. We observed improved angiogenesis and bone formation with the fabricated scaffolds compared with the control groups. Computed tomography (CT) scans and radiographic imaging, in addition to histology and immunohistochemical analyses, showed the presence of angiogenesis and bone regeneration after implantation of the ADSC-seeded scaffolds in a critical size calavarial bone defect in a Wistar rat model. We obtained the best in vitro and in vivo results by doping 2% Co2+ in HA. Taken together, we propose that the Co2+-doped HA/silk fibroin (SF) scaffold would be a good candidate to induce angiogenesis and bone formation both in vitro and in vivo.

Exosome loaded alginate hydrogel promotes tissue regeneration in full‐thickness skin wounds: An in vivo study

“…Adult male Wistar rats (weighing 250–300 g) were obtained from the Pasteur Institute (Tehran, Iran) and kept under standard conditions. The Ethics Committee of Tehran University of Medical Sciences approved all the animal experiments (ethical code: IR.TUMS.REC.1394.1594) (Fani et al, ).…”

“…Isolation of ADSCs was carried out according to ethical instruction of Tehran University of Medical Sciences, Tehran, Iran using previously described protocols (Fani et al, ). In brief, the abdominal adipose tissue was obtained from the healthy Wistar rat.…”

The Materiobiology of Silk: Exploring the Biophysical Influence of Silk Biomaterials on Directing Cellular Behaviors

“…Cobalt (Co 2+ ) has also been used as a dopant with silk owing to its unique ability to stimulate neovascularization. Co 2+ when used with HA/SF scaffold, makes a great candidate for inducing angiogenesis and bone formation in vitro and in vivo ( Fani et al, 2019 ). Therefore, inorganic elements can also be utilized in silk scaffolds to guide cellular differentiation.…”

Immobilization of cobalt‐loaded laponite/carboxymethyl chitosan on polycaprolactone nanofiber for improving osteogenesis and angiogenesis activities

“…The treatment of large bone defects due to trauma, infections, tumors, or genetic malformations, represents a major challenge for clinicians 28 . Promoting bone tissue regeneration through enhanced osteogenesis and angiogenesis is a desirable property of some biomaterials for bone repair 29 . In the previous study, we showed that immobilized CMC/LAP on PCL nanofibers could significantly support the proliferation and differentiation of stem cells to osteoblasts without using any external osteoinductive agent 18 .…”