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Guiding morphogenesis in cell-instructive microgels for therapeutic angiogenesis.

A L Torres1, S J Bidarra2, M T Pinto3

  • 1i3S - Instituto de Inovação e Investigação em Saúde, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

Biomaterials
|November 10, 2017
PubMed
Summary

This study developed injectable alginate microgels that guide cell self-assembly for therapeutic angiogenesis. These engineered microtissues promote blood vessel formation and integrate with host vasculature after implantation.

Keywords:
Cell therapyCell-instructiveInjectable biomaterialMicrotissuePre-vascularization

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Vascular Biology

Background:

  • Cell-based therapies require efficient delivery systems for improved therapeutic outcomes.
  • Developing injectable platforms that guide cell organization is crucial for pro-angiogenic treatments.

Purpose of the Study:

  • To design an injectable, biomaterial-guided cell delivery platform for therapeutic angiogenesis.
  • To investigate the role of microgel properties and in vitro priming on cell assembly and vascularization.

Main Methods:

  • Fabrication of functionalized alginate microgels with specific biochemical and biomechanical cues.
  • Co-culture of mesenchymal stem cells and outgrowth endothelial cells (OEC) within microgels.
  • In vitro priming of OECs under normoxia with growth factors to induce tubulogenesis.
  • In vivo implantation in chick embryos to assess vascularization and host integration.

Main Results:

  • Functionalized alginate microgels facilitated the co-assembly of stem cells and OECs into pre-vascularized microtissues.
  • In vitro priming under normoxia and growth factors induced stable OEC tubulogenesis, resistant to ischemic conditions.
  • Primed cells secreted pro-angiogenic factors and produced an extracellular matrix, creating a stable angiogenic niche.
  • Implanted microgels promoted host-microtissue interaction, with detected human vascular structures and cell integration in vivo.

Conclusions:

  • An integrated approach using pro-angiogenic cells, instructive microgels, and optimized in vitro priming shows promise for therapeutic angiogenesis.
  • This injectable platform supports the formation of stable vascular networks and host integration, paving the way for advanced cell therapies.