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Engineered VEGF-releasing PEG–MAL hydrogel for pancreatic islet vascularization

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Abstract

Biofunctionalized polyethylene glycol maleimide (PEG–MAL) hydrogels were engineered as a platform to deliver pancreatic islets to the small bowel mesentery and promote graft vascularization. VEGF, a potent stimulator of angiogenesis, was incorporated into the hydrogel to be released in an on-demand manner through enzymatic degradation. PEG–MAL hydrogel enabled extended in vivo release of VEGF. Isolated rat islets encapsulated in PEG–MAL hydrogels remained viable in culture and secreted insulin. Islets encapsulated in PEG–MAL matrix and transplanted to the small bowel mesentery of healthy rats grafted to the host tissue and revascularized by 4 weeks. Addition of VEGF release to the PEG–MAL matrix greatly augmented the vascularization response. These results establish PEG–MAL engineered matrices as a vascular-inductive cell delivery vehicle and warrant their further investigation as islet transplantation vehicles in diabetic animal models.

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Acknowledgments

Funding for this work was provided by NIH (R01-EB004496), Georgia Tech/Emory Center (GTEC) for the Engineering of Living Tissues, and the Atlanta Clinical and Translational Science Institute (ACTSI) supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources, National Science Foundation under the Science and Technology Center Emergent Behaviors of Integrated Cellular Systems (EBICS) Grant No. CBET-0939511; AHA predoctoral fellowship (E.A.P.).

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  1. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA

    Edward A. Phelps, Kellie L. Templeman & Andrés J. García

  2. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA, 30332, USA

    Edward A. Phelps, Kellie L. Templeman, Peter M. Thulé & Andrés J. García

  3. Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road NE, Decatur, GA, 30033, USA

    Peter M. Thulé

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Phelps, E.A., Templeman, K.L., Thulé, P.M. et al. Engineered VEGF-releasing PEG–MAL hydrogel for pancreatic islet vascularization. Drug Deliv. and Transl. Res. 5, 125–136 (2015). https://doi.org/10.1007/s13346-013-0142-2

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