Chen, C.-Y.C.-Y.ChenKe, C.-J.C.-J.KeYen, K.-C.K.-C.YenHsieh, H.-C.H.-C.HsiehJUI-SHENG SUNFENG-HUEI LIN2020-02-072020-02-0720151838-7640https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930622801&doi=10.7150%2fthno.11372&partnerID=40&md5=bf3f40770c89023ef36294a4a41206cchttps://scholars.lib.ntu.edu.tw/handle/123456789/455316Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects. ? 2015 Ivyspring International Publisher.[SDGs]SDG3alkaline phosphatase; beta 2 microglobulin; calcium alginate; collagen type 1; edetic acid; messenger RNA; osteocalcin; transcription factor RUNX2; alginic acid; glucuronic acid; hexuronic acid; Alp1 gene; Article; autotransplantation; B2M gene; Bglap gene; bioreactor; bone density; bone development; bone mass; cell proliferation; cell transplantation; cell viability; chelation; Col1a1 gene; controlled study; crystallization; culture technique; gene expression regulation; human; human cell; osteoblast; porosity; process development; Runx2 gene; scanning electron microscopy; three dimensional cell culture system; three dimensional imaging; tissue engineering; tissue scaffold; cell culture; chemistry; cytology; devices; drug effects; osteoblast; physiology; procedures; tissue scaffold; Alginates; Bioreactors; Cell Proliferation; Cells, Cultured; Glucuronic Acid; Hexuronic Acids; Humans; Osteoblasts; Tissue Engineering; Tissue Scaffoldsjournal article10.7150/thno.11372258256032-s2.0-84930622801