Scaffold Architecture and Matrix Strain Modulate Mesenchymal Cell and Microvascular Growth and Development in a Time Dependent Manner.
Bone
Capillaries
Scaffold
Stroma
Vascularization
Journal
Cellular and molecular bioengineering
ISSN: 1865-5025
Titre abrégé: Cell Mol Bioeng
Pays: United States
ID NLM: 101468590
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
15
02
2020
accepted:
11
08
2020
entrez:
13
11
2020
pubmed:
14
11
2020
medline:
14
11
2020
Statut:
epublish
Résumé
Volumetric tissue-engineered constructs are limited in development due to the dependence on well-formed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis. The interaction between mesenchymal stem cells (MSCs) seeded on hydroxyapatite scaffolds of 450, 340, and 250 μm pores and microvascular fragments (MVFs) seeded within 20 mg/mL fibrin hydrogels that were cast into the cell-seeded scaffolds, was assessed Lectin staining of decalcified scaffolds showed continued vessel growth, branching and network formation at 14 days. The fibrin gel provides no resistance to spread-out capillary networks formation, with greater vessel loops within the 450 μm pores and vessels bridging across 250 μm pores. Vessel growth in the scaffolds was observed to be stimulated by hypoxia and successive angiogenic signaling. Fibrin gels showed linear fold increase in VEGF expression and no change in BMP2. Within scaffolds, there was multiple fold increase in VEGF between days 7 and 14 and early multiple fold increases in BMP2 between days 3 and 7, relative to fibrin. There was evidence of yap/taz based hippo signaling and mechanotransduction in the scaffold groups. The vessel growth models determined by computational modeling matched the trends observed experimentally. The differing nature of hypoxia signaling between scaffold systems and mechano-transduction sensing matrix mechanics were primarily responsible for differences in osteogenic cell and microvessel growth. The computational model implicated scaffold architecture in dictating branching morphology and strain in the hydrogel within pores in dictating vessel lengths.
Sections du résumé
BACKGROUND
BACKGROUND
Volumetric tissue-engineered constructs are limited in development due to the dependence on well-formed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis.
METHODS
METHODS
The interaction between mesenchymal stem cells (MSCs) seeded on hydroxyapatite scaffolds of 450, 340, and 250 μm pores and microvascular fragments (MVFs) seeded within 20 mg/mL fibrin hydrogels that were cast into the cell-seeded scaffolds, was assessed
RESULTS
RESULTS
Lectin staining of decalcified scaffolds showed continued vessel growth, branching and network formation at 14 days. The fibrin gel provides no resistance to spread-out capillary networks formation, with greater vessel loops within the 450 μm pores and vessels bridging across 250 μm pores. Vessel growth in the scaffolds was observed to be stimulated by hypoxia and successive angiogenic signaling. Fibrin gels showed linear fold increase in VEGF expression and no change in BMP2. Within scaffolds, there was multiple fold increase in VEGF between days 7 and 14 and early multiple fold increases in BMP2 between days 3 and 7, relative to fibrin. There was evidence of yap/taz based hippo signaling and mechanotransduction in the scaffold groups. The vessel growth models determined by computational modeling matched the trends observed experimentally.
CONCLUSION
CONCLUSIONS
The differing nature of hypoxia signaling between scaffold systems and mechano-transduction sensing matrix mechanics were primarily responsible for differences in osteogenic cell and microvessel growth. The computational model implicated scaffold architecture in dictating branching morphology and strain in the hydrogel within pores in dictating vessel lengths.
Identifiants
pubmed: 33184580
doi: 10.1007/s12195-020-00648-7
pii: 648
pmc: PMC7596170
doi:
Types de publication
Journal Article
Langues
eng
Pagination
507-526Subventions
Organisme : NIDCR NIH HHS
ID : R21 DE030603
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM060655
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR002647
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002645
Pays : United States
Organisme : NIDDK NIH HHS
ID : SC1 DK122578
Pays : United States
Organisme : NIH HHS
ID : S10 OD021805
Pays : United States
Informations de copyright
© Biomedical Engineering Society 2020.
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