Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

Lee, Jangwook; Bhang, Suk Ho; Park, Honghyun; Kim, Byung Soo; Lee, Kuen Yong

doi:10.1007/s11095-010-0067-0

Cited by 56 publications

(37 citation statements)

References 37 publications

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“…Currently, only poly(d,l-lactide-co-glycolide) (PLGA), collagen-fibronectin, alginate, gelatin, fibrin, and peptide amphiphiles have been examined (Doi et al, 2007;Jay et al, 2008;Kong et al, 2008;Layman et al, 2007;Lee et al, 2010;Ruvinov et al, 2010;Silva and Mooney, 2007;Webber et al, 2011). PLGA microspheres in alginate hydrogels have been utilized to deliver vascular endothelial growth factor (VEGF) (Lee et al, 2010), and alginate hydrogels have been explored for delivery of hepatocyte growth factor (HGF) (Ruvinov et al, 2010), VEGF (Silva and Mooney, 2007), and pDNA encoding for VEGF (Kong et al, 2008). Alginate microspheres within an injectable collagen matrix have also been used to deliver stromal cell-derived factor-1 (SDF-1) (Kuraitis et al, 2011), while VEGF-loaded alginate microparticles in a collagen-fibronectin scaffold were used to deliver endothelial cells (Jay et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Previous biomaterial strategies for PAD have only utilized scaffolds to enhance cell or growth factor therapy (Doi et al, 2007;Jay et al, 2008;Kong et al, 2008;Layman et al, 2007;Lee et al, 2010;Ruvinov et al, 2010;Silva and Mooney, 2007). However, a lone biomaterial therapy has several benefits, which may allow it to reach patients sooner, including the potential to be an off-the-shelf treatment without the complications that both cells and growth factors can add.…”

Section: Discussionmentioning

confidence: 99%

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Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

DeQuach

Lin²,

Cam³

et al. 2012

eCM

140

159

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Peripheral artery disease (PAD) currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI), which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold's degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 µL of skeletal muscle matrix or collagen 1 week postinjury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue-specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

DeQuach

Lin²,

Cam³

et al. 2012

eCM

140

159

View full text Add to dashboard Cite

show abstract

“…Each sample was immerged in 3.5 mL of PBS (pH 7.4) and incubated at 37°C under continuous agitation. After 1,2,4,6,8,12,16,20,24,28,32,36, and 40 days, the supernatant of each specimen was collected for ELISA tests (R&D, Minneapolis, MN, USA). The total VEGF incorporated was determined by extracting dry VEGF-NP at room temperature with ethyl alcohol.…”

Section: In Vitro and In Vivo Drug Release Studiesmentioning

confidence: 99%

Induction of Angiogenesis by Controlled Delivery of Vascular Endothelial Growth Factor Using Nanoparticles

Xie

Wang

et al. 2013

Cardiovascular Therapeutics

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Summary Aims The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex‐GMA) and gelatin for therapeutic angiogenesis. Methods The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF‐incorporated nanoparticles (VEGF‐NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single‐photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry. Results The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1–12 days. Tube formation assays showed increased tubular structures by VEGF‐NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF‐NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF‐NP‐treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF‐NP‐treated limbs. Conclusions Dex‐GMA and gelatin‐based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.

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“…Particles prepared with the Poly(lactic-co-glycolic acid) (PLGA) copolymer have been widely used due to the excellent biocompatibility and biodegradability of the material [79][80][81][82][83]. Benefits of using PLGA particles for angiogenesis have been shown in hindlimb ischemia models, resulting in increased blood vessel formation [84][85][86]. Also, the effect of delivery of PLGA microparticles loaded with VEGF-A 165 has been studied in a rat model of cardiac ischemia-reperfusion, demonstrating an increase in heart tissue angiogenesis and arteriogenesis, besides positive remodeling of the heart [63].…”

Section: Protein Therapymentioning

confidence: 99%

Cardiac Regeneration with Stem Cells

Pelacho

Mazo

Montori

et al. 2012

Regenerative Medicine and Cell Therapy

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Cardiovascular diseases (CVD) are the main causes of morbidity and mortality worldwide. A huge effort has been made to improve current standard approaches for treating patients with ischemic heart disease. However, despite the greater efficacy of new drugs and clinical techniques, which have decreased the number of acute patients and prolonged the life of chronic ones, the classic treatments are still not able to regenerate the diseased heart. For this reason, alternative therapies based on the use of gene, protein, and stem cells have been developed in combination with bioengineering techniques, with the aim not only of protecting but also repairing the damaged heart. All these new therapies, especially stem cell therapy and the possibility of combining these cells with biomaterials in order to reinforce their potential or even create new tissues, are reviewed in this chapter. Abbreviations AAVAdeno-associated virus ADSC

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Active Blood Vessel Formation in the Ischemic Hindlimb Mouse Model Using a Microsphere/Hydrogel Combination System

Abstract: A microsphere/hydrogel combination system provided a useful means to deliver therapeutic angiogenic molecules into the body for the treatment of ischemic vascular diseases, which could reduce the number of administrations of many types of drugs.

Cited by 56 publications

References 37 publications

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

Induction of Angiogenesis by Controlled Delivery of Vascular Endothelial Growth Factor Using Nanoparticles

Cardiac Regeneration with Stem Cells

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