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Journal of Controlled ReleaseVolume 189, 10 September 2014, Pages 158-168

Hydrogel depots for local co-delivery of osteoinductive peptides and mesenchymal stem cells(Article)

  • aINEB - Instituto de Engenharia Biomédica, Rua do Campo Alegre, n. 823, 4150-180 Porto, Portugal
  • bFEUP - Faculdade de Engenharia Universidade Do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
  • cDepartamento de Química e Bioquímica, Faculdade de Ciências, Universidade Do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal
  • dICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade Do Porto, Rua de Jorge Viterbo Ferreira n.228, 4050-313 Porto, Portugal

Abstract

The outcome of cell-based therapies can benefit from carefully designed cell carriers. A multifunctional injectable vehicle for the co-delivery of human mesenchymal stem cells (hMSCs) and osteoinductive peptides is proposed, to specifically direct hMSCs osteogenic differentiation. The osteogenic growth peptide (OGP) inspired the design of two peptides, where the bioactive portion of OGP was flanked by a protease-sensitive linker, or its scrambled sequence, to provide faster and slower release rates, respectively. Peptides were fully characterized and chemically grafted to alginate. Both OGP analogs released bioactive fragments in vitro, at different kinetics, which stimulated hMSCs proliferation and osteogenesis. hMSCs-laden OGP-alginate hydrogels were tested at an ectopic site in a xenograft mouse model. After 4 weeks, OGP-alginate hydrogels were more degraded and colonized by vascularized connective tissue than the control (without OGP). hMSCs were able to proliferate, migrate outward the hydrogels, produce endogenous extracellular matrix and mineralize it. Moreover, OGP-groups stimulated hMSCs osteogenesis, as compared with the control. Overall, the ability of the proposed platform to direct the fate of transplanted hMSCs in loco was demonstrated, and OGP-releasing hydrogels emerged as a potentially useful system to promote bone regeneration. © 2014 Elsevier B.V.

Author keywords

Bone regenerationCo-delivery systemsGuided differentiationInjectable alginate hydrogelsMesenchymal stem cellsOsteoinductive peptides

Indexed keywords

Engineering controlled terms:AlginateCell cultureCollagenMusculoskeletal systemPeptidesStem cells
Engineering uncontrolled termsAlginate hydrogelsBone regenerationCo deliveriesMesenchymal stem cellOsteoinductive
Engineering main heading:Hydrogels
EMTREE drug terms:alginic acidalkaline phosphatasebiomaterialgelatinase Aglyceraldehyde 3 phosphate dehydrogenaseosteocalcinosteogenic growth peptide 1osteogenic growth peptide 2peptide derivativetranscription factor RUNX2unclassified drugvasculotropin 165alginic acidglucuronic acidhexuronic acidhistonehydrogelosteogenic growth peptidesignal peptide
EMTREE medical terms:amino acid sequenceanimal cellanimal experimentarticlebone developmentbone regenerationcell differentiationcell proliferationcell viabilityconnective tissuecontrolled studyextracellular matrixhigh performance liquid chromatographyhumanhuman cellhydrogelin vitro studyliquid chromatographymalemass spectrometrymesenchymal stem cell transplantationmousenonhumannucleotide sequencepriority journalprotein expressionadministration and dosageanimalcell culturechemistrycytologydrug delivery systemhydrogelmesenchymal stem cell transplantationmesenchymal stroma cellproceduresSCID mouse
MeSH:AlginatesAnimalsCell DifferentiationCells, CulturedDrug Delivery SystemsGlucuronic AcidHexuronic AcidsHistonesHumansHydrogelsIntercellular Signaling Peptides and ProteinsMaleMesenchymal Stem Cell TransplantationMesenchymal Stromal CellsMice, SCIDOsteogenesis

Molecular Sequence Numbers:

GENBANK,

AB021221(referenced), BC021289(referenced), NM_002046(referenced), NM_199173(referenced)

Chemicals and CAS Registry Numbers:

alginic acid, 28961-37-7, 29894-36-8, 9005-32-7, 9005-38-3; alkaline phosphatase, 9001-78-9; gelatinase A, 146480-35-5; glyceraldehyde 3 phosphate dehydrogenase, 9001-50-7; osteocalcin, 136461-80-8; glucuronic acid, 36116-79-7, 576-37-4, 6556-12-3; histone, 9062-68-4;

Alginates; alginic acid; Glucuronic Acid; Hexuronic Acids; Histones; Hydrogels; Intercellular Signaling Peptides and Proteins; osteogenic growth peptide

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de CompetitividadeCOMPETE
European Commission
See opportunities		PEst-C/QUI/UI0081/2011,CONC-REEQ/275/QUI
Fundação para a Ciência e a Tecnologia
See opportunities		Pest-C/SAU/LA0002/2011
DT/2011
Fundação para a Ciência e a Tecnologia
See opportunities
Ciência 2008
FCOMP-01-0124-FEDER-010915,PTDC/SAU-BEB/101235/2008

  • 1

    This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through Fundação para a Ciência e a Tecnologia ( FCT ), in the framework of the projects Pest-C/SAU/LA0002/2011 and BIOMATRIX ( PTDC/SAU-BEB/101235/2008 and FCOMP-01-0124-FEDER-010915 ), and co-financed by North Portugal Regional Operational Programme (ON.2–O Novo Norte) in the framework of project SAESCTN-PIIC&DT/2011 , under the National Strategic Reference Framework (NSRF). PG and NV thank FCT and FEDER (European Union) for funding through project grants CONC-REEQ/275/QUI and PEst-C/QUI/UI0081/2011 . NV also thanks FCT for Post-Doc grant SFRH/BPD/48345/2008 . FM acknowledges INL-International Iberian Nanotechnology Laboratory for her PhD scholarship. CB has a research position funded by FCT-POPH-FSE (Ciência 2008). The authors are also grateful to Drª Maria Aparecido (UNIFESP, Brazil) for providing the FRET peptides. Appendix A

  • ISSN: 01683659
  • CODEN: JCREE
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.jconrel.2014.06.030
  • PubMed ID: 24979208
  • Document Type: Article
  • Publisher: Elsevier

  Barrias, C.C.; Rua do Campo Alegre, 823, Portugal;
© Copyright 2014 Elsevier B.V., All rights reserved.

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