OBJECTIVE: Localized and sustained delivery of vascular endothelial growth factor (VEGF) is a promising approach to overcome the limited efficacy of bolus delivery. The authors examined the effects of host immune competence and local ischemia on the functionality of new vessel networks formed with this approach. METHODS: Vessel structure and perfusion resulting from implantation of porous 85:15 poly(lactide-co-glycolide) scaffolds releasing VEGF165 were measured in both subcutaneous tissue and ischemic hindlimbs of immune competent C57BL/6 and immune deficient SCID mice. RESULTS: Sustained VEGF delivery resulted in a similar approximately 100% increase in vessel density within scaffolds in both implant sites, and both animal models. However, the resulting perfusion within scaffolds implanted in subcutaneous tissue increased modestly versus control (18-35%), while perfusion increased 52-110% above control when VEGF-releasing scaffolds were placed in ischemic hindlimbs of C57BL/6 or SCID mice. VEGF delivery improved perfusion in the entire ischemic limb (55 +/- 18% of the normal value by week 6; 138% increase over control) in SCID mice. Although C57BL/6 mice demonstrated spontaneous recovery from ischemia, VEGF delivery accelerated recovery as compared to control. CONCLUSIONS: Localized and sustained VEGF delivery can create functional vasculature that amplifies recovery of tissue ischemia. However, increases in local and regional perfusion were highly dependent on the implantation site and the animal model.
OBJECTIVE: Localized and sustained delivery of vascular endothelial growth factor (VEGF) is a promising approach to overcome the limited efficacy of bolus delivery. The authors examined the effects of host immune competence and local ischemia on the functionality of new vessel networks formed with this approach. METHODS: Vessel structure and perfusion resulting from implantation of porous 85:15 poly(lactide-co-glycolide) scaffolds releasing VEGF165 were measured in both subcutaneous tissue and ischemic hindlimbs of immune competent C57BL/6 and immune deficient SCIDmice. RESULTS: Sustained VEGF delivery resulted in a similar approximately 100% increase in vessel density within scaffolds in both implant sites, and both animal models. However, the resulting perfusion within scaffolds implanted in subcutaneous tissue increased modestly versus control (18-35%), while perfusion increased 52-110% above control when VEGF-releasing scaffolds were placed in ischemic hindlimbs of C57BL/6 or SCIDmice. VEGF delivery improved perfusion in the entire ischemic limb (55 +/- 18% of the normal value by week 6; 138% increase over control) in SCIDmice. Although C57BL/6 mice demonstrated spontaneous recovery from ischemia, VEGF delivery accelerated recovery as compared to control. CONCLUSIONS: Localized and sustained VEGF delivery can create functional vasculature that amplifies recovery of tissue ischemia. However, increases in local and regional perfusion were highly dependent on the implantation site and the animal model.
Authors: Vivek A Kumar; Nichole L Taylor; Siyu Shi; Benjamin K Wang; Abhishek A Jalan; Marci K Kang; Navindee C Wickremasinghe; Jeffrey D Hartgerink Journal: ACS Nano Date: 2015-01-13 Impact factor: 15.881
Authors: Erin M Anderson; Brian J Kwee; Sarah A Lewin; Theresa Raimondo; Manav Mehta; David J Mooney Journal: Tissue Eng Part A Date: 2015-01-23 Impact factor: 3.845
Authors: Rekha Samuel; Laurence Daheron; Shan Liao; Trupti Vardam; Walid S Kamoun; Ana Batista; Christa Buecker; Richard Schäfer; Xiaoxing Han; Patrick Au; David T Scadden; Dan G Duda; Dai Fukumura; Rakesh K Jain Journal: Proc Natl Acad Sci U S A Date: 2013-07-16 Impact factor: 11.205
Authors: Vivek A Kumar; Qi Liu; Navindee C Wickremasinghe; Siyu Shi; Toya T Cornwright; Yuxiao Deng; Alon Azares; Amanda N Moore; Amanda M Acevedo-Jake; Noel R Agudo; Su Pan; Darren G Woodside; Peter Vanderslice; James T Willerson; Richard A Dixon; Jeffrey D Hartgerink Journal: Biomaterials Date: 2016-04-26 Impact factor: 12.479
Authors: Robert E Guldberg; Craig L Duvall; Alexandra Peister; Megan E Oest; Angela S P Lin; Ashley W Palmer; Marc E Levenston Journal: Biomaterials Date: 2008-07-16 Impact factor: 12.479