Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit ma
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Journal of Translational Medicine Open Access
RESEARCH
Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model Asrin Emami1, Tahereh Talaei‑Khozani1, Saeid Tavanafar2, Nehleh Zareifard1, Negar Azarpira3 and Zahra Vojdani1*
Abstract Background: Extracellular vesicles (ECV) and bone extracellular matrix (ECM) have beneficial effects on the treat‑ ment of some pathological conditions. The purpose of this study was to find the synergic effects of decellularized bone (DB) ECM and ECVs on the repair of rabbit. Methods: The quality of decellularized sheep bones was confirmed by H&E, Hoechst, DNA quantification, immu‑ nohistochemistry, histochemical staining, and scanning electron microscopy (SEM). Osteoblast-derived ECVs were evaluated by internalization test, Transmission electron microscopy, Dynamic light scattering, and flow cytometry for CD9, CD63, CD81 markers. The hydrogel containing DB and hydroxyapatite (HA) with or without ECVs was evaluated for osteoblast functions and bone repair both in vitro and in vivo. Results: The data indicated ECM preservation after decellularization as well as cell depletion. In vitro assessments revealed that mineralization and alkaline phosphatase activity did not improve after treatment of MG63 cells by ECVs, while in vivo morphomatrical estimations showed synergic effects of ECVs and DB + HA hydrogels on increasing the number of bone-specific cells and vessel and bone area compared to the control, DB + HA and ECV-treated groups. Conclusions: The DB enriched with ECVs can be an ideal scaffold for bone tissue engineering and may provide a suitable niche for bone cell migration and differentiation. Keywords: Decellularized bone, Extracellular vesicle, Hydroxyapatite, Tissue engineering Background Bone defect repairing is one of the major challenges in regenerative medicine. Despite the high repair capability, spontaneous restoration of vast bone defects does not perform well for specific conditions such as trauma, fractures, and crushing [1–3]. The gold standard of bone defects treatment is autogenic transplantation, especially *Correspondence: [email protected] 1 Tissue Engineering Lab, Anatomy Department, Shiraz University of Medical Sciences, Shiraz, Iran Full list of author information is available at the end of the article
from iliac bones [4]; however, allogeneic and xenogenic grafts have also been used for bone regeneration. Despite the success of autologous bone transplantation, some limitations such as compliance of the transplanted bone shape in donor position, increase in operation time, resorption of the transplanted bone, and unavailable bone source, especially in the children [5] have created motivations for replacement materials. Engineered tissues, which are fabricated using suitable biocompatible materials and contain tissue-specific or stem cells, have the ability to recover bone biological functions [6].
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