A Cell‐Based Self‐Assembly Approach for the Production of Human Osseous Tissues from Adipose‐Derived Stromal/Stem Cells

Abstract

Achieving optimal bone defect repair is a clinical challenge driving intensive research in the field of bone tissue engineering. Many strategies focus on seeding graft materials with progenitor cells prior to in vivo implantation. Given the benefits of closely mimicking tissue structure and function with natural materials, the authors hypothesize that under specific culture conditions, human adipose-derived stem/stromal cells (hASCs) can solely be used to engineer human reconstructed osseous tissues (hROTs) by undergoing osteoblastic differentiation with concomitant extracellular matrix production and mineralization. Therefore, the authors are developing a self-assembly methodology allowing the production of such osseous tissues. Three-dimensional (3D) tissues reconstructed from osteogenically-induced cell sheets contain abundant collagen type I and are 2.7-fold less contractile compared to non-osteogenically induced tissues. In particular, hROT differentiation and mineralization is reflected by a greater amount of homogenously distributed alkaline phosphatase, as well as higher calcium-containing hydroxyapatite (P < 0.0001) and osteocalcin (P < 0.0001) levels compared to non-induced tissues. Taken together, these findings show that hASC-driven tissue engineering leads to hROTs that demonstrate structural and functional characteristics similar to native osseous tissue. These highly biomimetic human osseous tissues will advantageously serve as a platform for molecular studies as well as for future therapeutic in vivo translation.

Innovative Human Three-Dimensional Tissue-Engineered Models as an Alternative to Animal Testing

“…ASCs have osteogenic potential. In recent years, a thin bone substitute has been produced using osteocytes with the self-assembly method [ 284 ]. ASCs also demonstrated the potential to produce blood vessels and treat scars; they have also been used to improve bladder tissues [ 285 , 286 , 287 ].…”

Preclinical Evaluation of BMP-9-Treated Human Bone-like Substitutes for Alveolar Ridge Preservation following Tooth Extraction

“…For in vitro and in vivo studies, substitutes were assigned to four experimental groups: stromal substitutes, bone-like substitutes, BMP-9-treated stromal substitutes, and BMP-9-treated bone-like substitutes ( Table 2 ). Tissues were obtained by seeding hASCs at a density of 4000 cells/cm 2 (Passage 7) in 6-well plates containing a peripheric anchorage device (Whatman paper, Fisher Scientific, Quebec City, QC, Canada), as previously described [ 23 , 24 , 25 , 61 ]. Cells were first grown in DMEM supplemented with 10% FBS, antibiotics, and 1.8 mM calcium chloride (CaCl 2 ) (basal stromal control medium).…”

“…Over the years, our research team has developed all-natural bone-like substitutes based on cell-assembled extracellular matrix components surrounding live osteogenically induced human adipose-derived stromal/stem cells (hASCs) [ 23 , 24 , 25 ]. The capacity to differentiate towards the osteogenic lineage had already been established for this mesenchymal cell population [ 26 ].…”

Bioprinting of tissue engineering scaffolds

“…Such examples are gelatin, fibrin, alginate, nanohydroxyapatite, PCL, and PLGA hydrogels. Galbraith et al 89 developed a self-assembled osseous biopaper using osteogenically differentiated hASCs. Osseous biopapers exhibited higher ALP activity than stromal biopapers after 5, 15, and 21 days.…”