Advertisement

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
Chapter

Abstract

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.

Keywords

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) 

References

  1. 1.
    Mistry AS, Mikos AG. Tissue engineering strategies for bone regeneration. Adv Biochem Eng Biotechnol. 2005;94:1–22.PubMedGoogle Scholar
  2. 2.
    Ling JL, Liu N, Shi JG, Liu Q, et al. Osteogenic scaffolds for bone reconstruction. BioResearch Open Access. 2012;1(3):137–44.CrossRefGoogle Scholar
  3. 3.
    Tran CT, Gargiulo C, Thao HD, Tuan HM, Filgueira L, Michael Strong D. Culture and differentiation of osteoblasts on coral scaffold from human bone marrow mesenchymal stem cells. Cell Tissue Bank. 2011;12(4):247–61.CrossRefGoogle Scholar
  4. 4.
    Fisher JN, Peretti GM, Scotti C. Stem cells for bone regeneration: from cell-based therapies to decellularised engineered extracellular matrices. Stem Cell Int. 2016;2016:1–15.CrossRefGoogle Scholar
  5. 5.
    O’Brien FJ, Farrell E, Waller MA, Connell I, et al. Scaffolds and cells: preliminary biomechanical analysis and results for the use of a collagen gag scaffold for bone tissue engineering. Topic Bio-Mech Eng. 2004:167–83.Google Scholar
  6. 6.
    Einhorn TA. Enhancement of fracture healing. J Bone Joint Surg. 1995;77:940–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Puska M, Aho AJ, Vallittu P. Polymer composites for bone reconstruction. Adv Compos Mater Anal Nat Man-Made Mater. 2009;3:55–74.Google Scholar
  8. 8.
    Carlsson AS, Magnusson B, Moller H. Metal sensitivity in patients with metal-to-plastic total hip arthroplasties. Acta Orthop Scand. 1980;51(1):57–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Thomas P, Thomsen M. Allergy diagnostics in implant intolerance. Orthopedics. 2008;37(2):131–5.Google Scholar
  10. 10.
    Gamblin AL, Brennan AM, Renaud A, Yagita H, Lezot F, et al. Bone tissue formation with human mesenchymal stem cells and biphasic calcium phosphate ceramics: the local implication of osteoclasts and macrophages. Biomaterials. 2014;35:9660–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Grage-Griebenow E, Flad HD, Ernst M. Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol. 2001;69:11e20.Google Scholar
  12. 12.
    Adutler-Lieber S, Ben-Mordechai T, Naftali-Shani N, Asher E, Loberman D, et al. Human macrophage regulation via interaction with cardiac adipose tissue-derived mesenchymal stromal cells. J Cardiovasc Pharmacol Ther. 2013;18:78e86.CrossRefGoogle Scholar
  13. 13.
    Nemeth K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15:42e9.Google Scholar
  14. 14.
    Alexander KA, Chang MK, Maylin ER, Kohler T, et al. Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model. J Bone Min Res. 2011;26:1517–32.CrossRefGoogle Scholar
  15. 15.
    Benoit DS, Schwartz MP, Durney AR, Anseth KS. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater. 2008;7(10):816–23.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Shih YRV, Hwang YS, Phadke A, Kang H, et al. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. PNAS. 2014;111(3):990–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Peng G, Haoqiang Z, Yun L, Bo F, et al. Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo. Sci Rep. 2016;6:23367.CrossRefGoogle Scholar
  18. 18.
    Chang YL, Stanford CM, Keller JC. Calcium and phosphate supplementation promotes bone cell mineralization: implications for hydroxyapatite (HA)-enhanced bone formation. J Biomed Mater Res. 2000;52(2):270–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Gargiulo C, Pham VH, Hai NT, Nguyen NCD, Pham VP, Abe K, Flores V, Shifman M. Isolation and characterization of multipotent and pluripotent stem cells from human peripheral blood. Stem Cell Discov. 2015;5(3):1–17.CrossRefGoogle Scholar
  20. 20.
    Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol. 2014;14(1):15–56.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Panaroni C, Tzeng YS, Saeed H, Wu JY. Mesenchymal progenitors and the osteoblast lineage in bone marrow hematopoietic niches. Curr Osteoporos Rep. 2014;12(1):22–32.PubMedPubMedCentralCrossRefGoogle Scholar

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

Personalised recommendations