Functional Critical-Size Bone Tissue-Engineered Constructs by Integration of Treated Human Adipose Stem Cells with Osteoinductive, Seeded on 3D Printed Scaffold, Cultured in a Perfusion Bioreactor

Background and Aim: Bone tissue engineering aims to regenerate newfunctional bone using cells, scaffolds, bioreactors, osteostimulatory,osteoinductive, and pro-angiogenic factors. In this study, we delineate,from an engineering perspective, the progress that has been made toovercome the main challenges in the field of critical-size bone tissueengineeredconstructs using human adipose stem cells (hASCs), 3Dprinted scaffold, modified perfusion bioreactor, osteoinductive and proangiogenicfactors.Methods: Modeling was performed to optimize the parameter ofbioreactor and foresight what will happen in vivo. hASCs were extractedfrom adipose tissue and treated with osteoinductive and pro-angiogenicfactors to induce osteogenic and angiogenic differentiation. Treatedcells were seeded on 3D printed scaffold which was made based on thedefect size and cultured in the modified perfusion bioreactor. After invitroculture, surgery was performed to implant bone tissue-engineeredconstructs. Cell proliferation and osteogenic differentiation wereanalyzed up to 3 weeks.Results: Osteostimulatory and pro-angiogenic factors stimulated hASCstoward osteogenic and angiogenic differentiation. Dynamic flow usingmodified perfusion bioreactors enhanced osteogenic differentiation ofhASCs via increasing alkaline phosphatase activity and upregulatingosteogenic and angiogenic markers.Conclusion: Treatment of hASCs with osteostimulatory, osteoinductive,and pro-angiogenic factors enhanced angiogenic and osteogenicdifferentiation of hASCs. Incorporation of treated hASCs into the 3Dprinted scaffolds was cultured within the modified perfusion bioreactorformed thicker and more uniform bone tissue-engineered constructs forimplantation which is a promising approach to treat patients with largebone defects.

کلیدواژه ها:

Bone ، Osteogenic differentiation ، Angiogenesis ، Human adipose stem cells ، 3D printed scaffold ، Modified perfusion bioreactor