Innovative Scaffold Solution for Bone Regeneration Made of Beta-Tricalcium Phosphate Granules, Autologous Fibrin Fold, and Peripheral Blood Stem Cells

  • Ciro Gargiulo Isacco
  • Kieu C. D. Nguyen
  • Andrea Ballini
  • Gregorio Paduanelli
  • Van H. Pham
  • Sergey K. Aityan
  • Melvin Schiffman
  • Toai C. Tran
  • Thao D. Huynh
  • Luis Filgueira
  • Vo Van Nhan
  • Gianna Dipalma
  • Francesco Inchingolo


The drawbacks of traditional bone defect treatments have prompted the exploration of bone tissue engineering. The use of porous biomaterial scaffolds from calcium, bio-ceramic, and other different polymers to induce and increase bone cell and tissue growth is a present hot topic. In bone transplantation, the use of biomaterials may be a solution to avoid the lack of donor sites for autografts and the risk of rejection with allograft procedures. Challenges and efforts involve the use of engineered biomaterials that can mimic both the mechanical and biological properties of real bone tissue, supporting the vascularization of the implanted site. β-Tricalcium phosphate (β-TCP) has been used by dentists and clinicians for a decade in clinical applications on over a thousand patients with different bone pathologies including mandibular and maxillary reconstruction. This study aimed to explore suitable combination of β-TCP granules, autologous fibrin from human peripheral blood (hPB), and autologous peripheral blood stem cells (PB-SCs) for the realization of a bioscaffold (Compact Bio-BoneR) for bone regeneration and identify an efficient method to establish it as effective osteo-regenerators. It has been assessed that human PB is an exceptional source of multiple type of stem cells including mesenchymal (MSCs), neural (NSCs), hematopoietic (HSCs), and embryonic like (ESCs) which may differentiate into different cell phenotypes such as osteoblasts, chondrocytes, adipocytes, myocytes, cardiomyocytes, and neurons. Isolated PB-SCs were induced into osteoblasts using β-TCP granules. Cultured PB-SCs were directly transferred and seeded into the scaffolds and induced to differentiate into osteoblasts. β-TCP granules with diameters of 1 mm and 1–2.5 mm were embedded in a fibrin gel matrix and PB-SCs were added successively. The bioscaffold was poured in culture with serum-free medium (SFM) for a period of 7–10 days. Improved proliferation of PB-SCs was assessed by the expression of multipotent and pluripotent stem cell biomarkers performed by flow cytometry analysis as CD34, CD45, CD90, CD105, and SSEA3; osteoblasts were assessed by the positive expression of immune stain as alizarin red (AR), von Kossa (VK), and alkaline phosphatase (ALP). This study provides an alternative to biofunctionalized scaffold that exhibits improved osteogenesis that can be extremely beneficial in dentistry and orthopedics.


β-Tricalcium phosphate (β-TCP) Autologous peripheral blood stem cells (PB-SCs) Bioscaffold Compact Bio-BoneR Mesenchymal stem cells (MSCs) Neural stem cells (NSCs) Hematopoietic stem cells (HSCs) Embryonic like stem cells (ESCs) 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ciro Gargiulo Isacco
    • 1
  • Kieu C. D. Nguyen
    • 2
  • Andrea Ballini
    • 3
  • Gregorio Paduanelli
    • 1
  • Van H. Pham
    • 4
    • 5
  • Sergey K. Aityan
    • 6
  • Melvin Schiffman
    • 7
  • Toai C. Tran
    • 8
  • Thao D. Huynh
    • 9
  • Luis Filgueira
    • 10
  • Vo Van Nhan
    • 11
    • 12
  • Gianna Dipalma
    • 1
  • Francesco Inchingolo
    • 1
  1. 1.Department of Interdisciplinary Medicine (DIM), School of MedicineUniversity of Bari Aldo MoroBariItaly
  2. 2.Department of Stem Cell ResearchHSC International ClinicHo Chi Minh CityVietnam
  3. 3.Department of Basic Medical Sciences, Neurosciences and Sense OrgansUniversity of Bari Aldo MoroBariItaly
  4. 4.Department of MicrobiologyNam Khoa-Bioteck Microbiology Laboratory and Research CenterHo Chi Minh CityVietnam
  5. 5.Department of MicrobiologyNam Khoa-Bioteck Microbiology Laboratory and Research CenterHo Chi Minh CityUSA
  6. 6.Multidisciplinary Research CenterLincoln UniversityOaklandUSA
  7. 7.TustinUSA
  8. 8.Stem Cells, Embryology and Immunity DepartmentPham Ngoc Thach University of MedicineHo Chi Minh CityVietnam
  9. 9.Department of Embryology, Genetics and Stem CellsPham Ngoc Thach University of MedicineHo Chi Minh CityVietnam
  10. 10.Faculty of Science and MedicineUniversity of FribourgFribourgSwitzerland
  11. 11.University of Pharmacy and MedicineHo Chi Minh CityVietnam
  12. 12.Nha Khoa Nham TamPoliclinic and International Dental Implant CenterHo Chi Minh CityVietnam

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