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Osteo-differentiation of human mesenchymal stem cells attached to natural latex proteins from the rubber tree Hevea brasiliensis on scaffold of polycaprolactone and polylactic acid (PCL/PLA) to bone xenografting

Grant number: 13/09055-2
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2013
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marco Andrey Cipriani Frade
Grantee:Guilherme Ferreira Caetano
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):14/23662-1 - Production of 3D scaffolds containing different concentrations of graphene, hydroxyapatite and tricalcium phosphate surface coated with human bone morphogenetic and P-1 latex proteins, BE.EP.DR


Bone defects assume importance in growing prevalence of chronic health conditions since fractures and critical defects should increase as the population ages. The bone healing depends on a dense vascular network that provides essential oxygen and nutrients, an important characteristic for the process of tissue regeneration. Conventional treatments require transplantation and extremely invasive approaches, therefore the challenge of development new therapies and treatments still growing. A promising proposal is to obtain tissue in laboratory using scaffolds for the growth and differentiation of mesenchymal stem cells and factors that enable a suitable neovascularization and osteoinduction for grafting. The protein fraction F1 from latex extracted from Hevea brasiliensis rubber tree exhibit important angiogenic and healing activity and low-cost, promising advantages for use in tissue engineering coupled with the multipotentiality of mesenchymal stem cells attached to the polycaprolactone and polylactic acid scaffold (PCL/PLA). In vitro stem cells will be isolated from human adipose tissue, expanded and characterized immunophenotypically. After that, cells will be seeded in scaffold of PCL/PLA to be cultured in the presence of normal culture media and osteogenic differentiation media in the presence and absence of F1 to evaluate cell adhesion, cell viability, osteogenic differentiation. The tissue growth and calcium deposition will be controlled by magnetic resonance imaging and computerized tomography scan of the samples, respectively. The scaffolds with cells will be implanted in rat calvarial bone model to evaluate the potential of biomaterials as bone substitute. Therefore, the objective of this work is to investigate in a preclinical study the interaction of F1 fraction from latex in human mesenchymal stem cells derived from adipose tissue (ADSCs) cultured in scaffold of PCL/PLA for osteogenic differentiation and its efficacy and safety as bone repair for use in future clinical studies.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAETANO, GUILHERME; VIOLANTE, RICARDO; SANT'ANA, ANA BEATRIZ; MURASHIMA, ADRIANA BATISTA; DOMINGOS, MARCO; GIBSON, ANDREW; BARTOLO, PAULO; FRADE, MARCO ANDREY. Cellularized versus decellularized scaffolds for bone regeneration. Materials Letters, v. 182, p. 318-322, . (13/20554-0, 13/09055-2)
CAETANO, GUILHERME; WANG, WEIGUANG; MURASHIMA, ADRIANA; PASSARINI, JR., JOSE ROBERTO; BAGNE, LEONARDO; LEITE, MARCEL; HYPPOLITO, MIGUEL; AL-DEYAB, SALEM; EL-NEWEHY, MOHAMED; BARTOLO, PAULO; et al. Tissue Constructs with Human Adipose-Derived Mesenchymal Stem Cells to Treat Bone Defects in Rats. MATERIALS, v. 12, n. 14, . (13/20554-0, 13/09055-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAETANO, Guilherme Ferreira. Adipose-derived multipotent stromal cells and natural latex protein fraction (Hevea brasiliensis) associated with polycaprolactone and graphene scaffolds in experimental osteogenesis. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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