PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation

Claudia Navarro-Requena, Jessica D. Weaver, Amy Y. Clark, Douglas A. Clift, Soledad Pérez-Amodio, Óscar Castaño, Dennis W. Zhou, Andrés J. García, Elisabeth Engel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The use of human mesenchymal stromal cells (hMSC) for treating diseased tissues with poor vascularization has received significant attention, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have also been suggested as therapeutic agents for stimulating angiogenesis in soft tissues, but these effects need further evaluation in vivo. In this study, calcium-releasing particles and hMSC were combined within a hydrogel to examine their vasculogenic potential in vitro and in vivo. The particles provided sustained calcium release and showed proangiogenic stimulation in a chorioallantoic membrane (CAM) assay. The number of hMSC encapsulated in a degradable RGD-functionalized PEG hydrogel containing particles remained constant over time and IGF-1 release was increased. When implanted in the epidydimal fat pad of immunocompromised mice, this composite material improved cell survival and stimulated vessel formation and maturation. Thus, the combination of hMSC and calcium-releasing glass-ceramics represents a new strategy to achieve vessel stabilization, a key factor in the revascularization of ischemic tissues. Statement of Significance: Increasing blood vessel formation in diseased tissues with poor vascularization is a current clinical challenge. Cell therapy using human mesenchymal stem cells has received considerable interest, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have been explored as therapeutic agents for stimulating angiogenesis in soft tissues, but these effects need further evaluation in vivo. By incorporating both human mesenchymal stem cells and glass-ceramic particles in an implantable hydrogel, this study provides insights into the vasculogenic potential in soft tissues of the combined strategies. Enhancement of vessel formation and maturation supports further investigation of this strategy.

Original languageEnglish (US)
Pages (from-to)53-65
Number of pages13
JournalActa Biomaterialia
Volume67
DOIs
StatePublished - Feb 2018
Externally publishedYes

Fingerprint

Hydrogel
Mesenchymal Stromal Cells
Hydrogels
Particles (particulate matter)
Polyethylene glycols
Calcium
Glass ceramics
Tissue
Cell Survival
Bioactive glass
Angiogenesis Inducing Agents
Cells
Stem cells
Chorioallantoic Membrane
Blood vessels
Cell- and Tissue-Based Therapy
Oils and fats
Insulin-Like Growth Factor I
Blood Vessels
Adipose Tissue

Keywords

  • Calcium
  • Glass-ceramic particles
  • hMSC
  • Hydrogel
  • Vascularization

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation. / Navarro-Requena, Claudia; Weaver, Jessica D.; Clark, Amy Y.; Clift, Douglas A.; Pérez-Amodio, Soledad; Castaño, Óscar; Zhou, Dennis W.; García, Andrés J.; Engel, Elisabeth.

In: Acta Biomaterialia, Vol. 67, 02.2018, p. 53-65.

Research output: Contribution to journalArticle

Navarro-Requena, C, Weaver, JD, Clark, AY, Clift, DA, Pérez-Amodio, S, Castaño, Ó, Zhou, DW, García, AJ & Engel, E 2018, 'PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation', Acta Biomaterialia, vol. 67, pp. 53-65. https://doi.org/10.1016/j.actbio.2017.12.009
Navarro-Requena, Claudia ; Weaver, Jessica D. ; Clark, Amy Y. ; Clift, Douglas A. ; Pérez-Amodio, Soledad ; Castaño, Óscar ; Zhou, Dennis W. ; García, Andrés J. ; Engel, Elisabeth. / PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation. In: Acta Biomaterialia. 2018 ; Vol. 67. pp. 53-65.
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AU - Weaver, Jessica D.

AU - Clark, Amy Y.

AU - Clift, Douglas A.

AU - Pérez-Amodio, Soledad

AU - Castaño, Óscar

AU - Zhou, Dennis W.

AU - García, Andrés J.

AU - Engel, Elisabeth

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AB - The use of human mesenchymal stromal cells (hMSC) for treating diseased tissues with poor vascularization has received significant attention, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have also been suggested as therapeutic agents for stimulating angiogenesis in soft tissues, but these effects need further evaluation in vivo. In this study, calcium-releasing particles and hMSC were combined within a hydrogel to examine their vasculogenic potential in vitro and in vivo. The particles provided sustained calcium release and showed proangiogenic stimulation in a chorioallantoic membrane (CAM) assay. The number of hMSC encapsulated in a degradable RGD-functionalized PEG hydrogel containing particles remained constant over time and IGF-1 release was increased. When implanted in the epidydimal fat pad of immunocompromised mice, this composite material improved cell survival and stimulated vessel formation and maturation. Thus, the combination of hMSC and calcium-releasing glass-ceramics represents a new strategy to achieve vessel stabilization, a key factor in the revascularization of ischemic tissues. Statement of Significance: Increasing blood vessel formation in diseased tissues with poor vascularization is a current clinical challenge. Cell therapy using human mesenchymal stem cells has received considerable interest, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have been explored as therapeutic agents for stimulating angiogenesis in soft tissues, but these effects need further evaluation in vivo. By incorporating both human mesenchymal stem cells and glass-ceramic particles in an implantable hydrogel, this study provides insights into the vasculogenic potential in soft tissues of the combined strategies. Enhancement of vessel formation and maturation supports further investigation of this strategy.

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