Engineered human vascularized constructs accelerate diabetic wound healing

Yu I. Shen, Hongkwan Cho, Arianne E. Papa, Jacqueline A. Burke, Xin Yi Chan, Elia J Duh, Sharon Gerecht

Research output: Contribution to journalArticle

Abstract

Stem cell-based therapy is emerging as a promising approach for chronic diabetic wounds, but strategies for optimizing both cellular differentiation and delivery remain as major obstacles. Here, we study bioengineered vascularized constructs as a therapeutic modality for diabetic wound healing. We developed a wound model in immunodeficient rodent and treated it with engineered vascularized constructs from endothelial progenitors or early vascular cells-derived from human induced pluripotent stem cells (hiPSCs) reprogrammed either from healthy donor or type-1 diabetic patient. We found that all vascularized constructs expedited wound closure and reperfusion, with endothelial progenitor constructs having the earliest maximum closure rate followed closely by healthy and diabetic hiPSC-derivative constructs. This was accompanied by rapid granulation layer formation and regression in all vascularized construct groups. Macrophage infiltration into the hydrogel matrix occurred during early stages of healing, seeming to facilitate rapid neovascularization of the wound that could then better persist in the vascularized constructs. Blood perfusion of the human vasculature could be detected after three days, indicating rapid integration with the host vasculature. Overall, we propose a potential therapeutic strategy using allograft or autologous vascularized constructs to treat type-1 diabetic wounds. This approach highlights the unprecedented prospects of designing patient-specific stem cell therapy.

Original languageEnglish (US)
Pages (from-to)107-119
Number of pages13
JournalBiomaterials
Volume102
DOIs
StatePublished - Sep 1 2016

Fingerprint

Stem cells
Wound Healing
Wounds and Injuries
Induced Pluripotent Stem Cells
Cell- and Tissue-Based Therapy
Granulation
Macrophages
Hydrogel
Infiltration
Hydrogels
Stem Cells
Allografts
Blood
Derivatives
Reperfusion
Blood Vessels
Rodentia
Perfusion
Tissue Donors
Therapeutics

Keywords

  • Hyaluronan
  • Hydrogel
  • Induced pluripotent stem cell
  • Type 1 diabetes
  • Wound healing

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Engineered human vascularized constructs accelerate diabetic wound healing. / Shen, Yu I.; Cho, Hongkwan; Papa, Arianne E.; Burke, Jacqueline A.; Chan, Xin Yi; Duh, Elia J; Gerecht, Sharon.

In: Biomaterials, Vol. 102, 01.09.2016, p. 107-119.

Research output: Contribution to journalArticle

Shen, Yu I. ; Cho, Hongkwan ; Papa, Arianne E. ; Burke, Jacqueline A. ; Chan, Xin Yi ; Duh, Elia J ; Gerecht, Sharon. / Engineered human vascularized constructs accelerate diabetic wound healing. In: Biomaterials. 2016 ; Vol. 102. pp. 107-119.
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