Combinatorial and sequential growth factor delivery
Recent studies have demonstrated that delivering multiple proangiogenic
GFs either in tandem or sequentially can help to
stimulate rapid neovascularization during wound healing. Recently,
our group used dextran hydrogels to deliver a combination of
VEGF, ANG1, SDF1 and IGF during subcutaneous wound healing
(Sun et al., 2011). The rats transplanted with these four factors
displayed significantly more and larger functional vessels in the
hydrogel compared with other groups.We also examined individual
GFs and various combinations of these GFs and found that VEGF
delivery is required for functional neovascularization, which is
enhanced by supplementary pro-angiogenic GFs.
A similar approach was reported by Mooney and colleagues
(Brudno et al., 2013). They investigated the effects of a temporally
regulated presentation of pro-angiogenic factors VEGF and ANG2
plus additional pro-maturation factors PDGF and ANG1 on
angiogenesis both in vitro and in vivo. Initially, they found that,
whereas VEGF and ANG2 stimulated EC sprouting and perivascular
cell detachment within a fibrin gel, simultaneous delivery of PDGF
and ANG1 inhibited this process. Similarly, whereas VEGF and
ANG2 enhanced microvascular density in a subcutaneous model of
blood vessel formation, simultaneous injection of PDGF and ANG1
significantly inhibited microvessel formation. However, the
sequential delivery of PDGF and ANG1 after delivery of VEGF
and ANG2 promoted both vessel maturation and remodeling without
inhibiting sprout angiogenesis. These results demonstrated that
sequentially controlled delivery of multiple GFs could be an
important strategy for promoting vessel maturation and remodeling.
Combinatorial and sequential growth factor deliveryRecent studies have demonstrated that delivering multiple proangiogenicGFs either in tandem or sequentially can help tostimulate rapid neovascularization during wound healing. Recently,our group used dextran hydrogels to deliver a combination ofVEGF, ANG1, SDF1 and IGF during subcutaneous wound healing(Sun et al., 2011). The rats transplanted with these four factorsdisplayed significantly more and larger functional vessels in thehydrogel compared with other groups.We also examined individualGFs and various combinations of these GFs and found that VEGFdelivery is required for functional neovascularization, which isenhanced by supplementary pro-angiogenic GFs.A similar approach was reported by Mooney and colleagues(Brudno et al., 2013). They investigated the effects of a temporallyregulated presentation of pro-angiogenic factors VEGF and ANG2plus additional pro-maturation factors PDGF and ANG1 onangiogenesis both in vitro and in vivo. Initially, they found that,whereas VEGF and ANG2 stimulated EC sprouting and perivascularcell detachment within a fibrin gel, simultaneous delivery of PDGFand ANG1 inhibited this process. Similarly, whereas VEGF andANG2 enhanced microvascular density in a subcutaneous model ofblood vessel formation, simultaneous injection of PDGF and ANG1significantly inhibited microvessel formation. However, thesequential delivery of PDGF and ANG1 after delivery of VEGFand ANG2 promoted both vessel maturation and remodeling withoutinhibiting sprout angiogenesis. These results demonstrated thatsequentially controlled delivery of multiple GFs could be animportant strategy for promoting vessel maturation and remodeling.
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