Thermosensitive Hydrogel as a Tgf- 1 Gene Delivery Vehicle Enhances Diabetic Wound Healing

Lee, Pui Yan; Li, Zhenhua; Huang, Leaf

doi:10.1023/b:pham.0000008048.58777.da

Cited by 115 publications

(56 citation statements)

References 17 publications

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“…This is why the use of biodegradable polymers, e.g., PLA, PLGA and PGA, has gained importance. The use of PEG-PLGA-PEG hydrogel for the delivery of plasmid-beta 1 gene increased the wound-healing process in a diabetic mouse model [73]. Meilander-Lin and co-workers reported similar results with agarose hydrogels.…”

Section: Application Of Hydrogels For Gene Deliverymentioning

confidence: 76%

Polymeric Hydrogels: Characterization and Biomedical Applications

Pal

Banthia

Majumdar

2009

Designed Monomers and Polymers

297

182

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Hydrogels are cross-linked polymeric networks, which have the ability to hold water within the spaces available among the polymeric chains. The hydrogels have been used extensively in various biomedical applications, e.g., drug delivery, cell carriers and/or entrapment, wound management and tissue engineering. Though far from extensive, this article has been devoted to study the common methods used for the characterization of the hydrogels and to review the range of applications of the same in health care.

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Section: Application Of Hydrogels For Gene Deliverymentioning

confidence: 76%

Polymeric Hydrogels: Characterization and Biomedical Applications

Pal

Banthia

Majumdar

2009

Designed Monomers and Polymers

297

182

View full text Add to dashboard Cite

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“…Temperature-sensitive PEG-PLLA-PEG FITC-labeled dextran [9] PEG-PLGA-PEG Spironolactone, ketoprofen [91] Plasmid DNA [92] Plasmid TGF-b1 [93] FITC [94] PLGA-PEG-PLGA Insulin [95] (ReGel 1 ) GLP-1 [96] Testosterone [97] Indomethacin, 5-fluorouracil [98] Ganciclovir [99] Levonorgestrel, interleukin-2,…”

Section: Hydrogel Types Polymer Delivery/applications Referencesmentioning

confidence: 99%

“…A plasmid TGF-b1-loaded PEG-PLGA-PEG hydrogel was used to accelerate wound healing in diabetic mice. [93] Reepithelialization was complete at day 9 using hydrogels containing TGF-b1, at day 11 employing a commercial wound dressing (Humatrix) that contained TGF-b1, and at day 14 in the absence of treatment. Fibroblast proliferation and collagen organization were significantly enhanced by hydrogel treatment relative to treatment with TGF-b1-loaded Humatrix.…”

Section: Temperature-sensitive Block Copolymer Hydrogelsmentioning

confidence: 99%

Injectable Biodegradable Hydrogels

Nguyen

Lee

2010

Macromolecular Bioscience

419

343

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Injectable biodegradable copolymer hydrogels, which exhibit a sol–gel phase transition in response to external stimuli, such as temperature changes or both pH and temperature (pH/temperature) alterations, have found a number of uses in biomedical and pharmaceutical applications, such as drug delivery, cell growth, and tissue engineering. These hydrogels can be used in simple pharmaceutical formulations that can be prepared by mixing the hydrogel with drugs, proteins, or cells. Such formulations are administered in a straightforward manner, through site‐specific control of release behavior, and the hydrogels are compatible with biological systems. This review will provide a summary of recent progress in biodegradable temperature‐sensitive polymers including polyesters, polyphosphazenes, polypeptides, and chitosan, and pH/temperature‐sensitive polymers such as sulfamethazine‐, poly(β‐amino ester)‐, poly(amino urethane)‐, and poly(amidoamine)‐based polymers. The advantages of pH/temperature‐sensitive polymers over simple temperature‐sensitive polymers are also discussed. A perspective on the future of injectable biodegradable hydrogels is offered.magnified image

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“…Many studies have used biomaterials to deliver growth factors or genes for regeneration of tissues including bone, 43 nerve, 44 skin, 45 and vasculature. 46,47 In particular, it was recently demonstrated that bi-domain peptides could be used to covalently attach small cell adhesion peptides 48,49 or heparin-binding growth factors, such as nerve growth factor or brain-derived neurotrophic factor, into fibrin gels.…”

mentioning

confidence: 99%

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

Geer

Swartz

Andreadis

2005

The American Journal of Pathology

111

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Exogenous keratinocyte growth factor (KGF) significantly enhances wound healing, but its use is hampered by a short biological half-life and lack of tissue selectivity. We used a biomimetic approach to achieve cell-controlled delivery of KGF by covalently attaching a fluorescent matrix-binding peptide that contained two domains: one recognized by factor XIII and the other by plasmin. Modified KGF was incorporated into the fibrin matrix at high concentration in a factor XIII-dependent manner. Cell-mediated activation of plasminogen to plasmin degraded the fibrin matrix and cleaved the peptides, releasing active KGF to the local microenvironment and enhancing epithelial cell proliferation and migration. To demonstrate in vivo effectiveness, we used a hybrid model of wound healing that involved transplanting human bioengineered skin onto athymic mice. At 6 weeks after grafting, the transplanted tissues underwent full thickness wounding and treatment with fibrin gels containing bound KGF. In contrast to topical KGF, fibrin-bound KGF persisted in the wounds for several days and was released gradually, resulting in significantly enhanced wound closure. A fibrinolytic inhibitor prevented this healing, indicating the requirement for cell-mediated fibrin degradation to release KGF. In conclusion, this biomimetic approach of localized, cell-controlled delivery of growth factors may accelerate healing of large full-thickness wounds and chronic wounds that are notoriously difficult to heal. Re-establishing an epithelial barrier in injured skin is a crucial wound-healing event that protects the body against further water loss and exposure to external pathogens. Skin epithelial cells or keratinocytes begin migrating to repair the epithelium ϳ18 to 24 hours after injury 1 carefully degrading a fibrin-rich clot through the activation of plasminogen into plasmin. 2 Transient interactions with extracellular matrix proteins in the wound such as collagen and fibronectin during fibrinolysis of the clot guide the keratinocytes into the wound space. Degranulating platelets are embedded in the fibrin matrix and release growth factors and cytokines, which activate keratinocytes to proliferate and migrate until they heal the defect.Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family (FGF-7), plays a prominent role in epithelial morphogenesis and wound healing. 3,4 Although initial studies restricted expression of KGF in cells of mesenchymal origin, 5,6 a recent study documented expression of KGF by dendritic epidermal T cells of the skin immediately after wounding, 7 suggesting that KGF may play an important role in epidermal immunity. The paracrine action of KGF on epithelial cells is mediated through the KGF receptor (KGFR or FGFR2IIIb), a splice variant of FGF-2 receptor encoded by the gene fgfr-2. 8,9 KGF is thought to be an important player in development and morphogenesis of epithelial tissues and a promoter of mesenchymal-epithelial interactions. 10,11 Targeting KGF expression to the basal keratinocyt...

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Thermosensitive Hydrogel as a Tgf- 1 Gene Delivery Vehicle Enhances Diabetic Wound Healing

Abstract: Thermosensitive hydrogel made of PEG-PLGA-PEG triblock copolymer provides excellent wound dressing activity and delivers plasmid TGF-beta1 to promote wound healing in a diabetic mouse model.

Cited by 115 publications

References 17 publications

Polymeric Hydrogels: Characterization and Biomedical Applications

Polymeric Hydrogels: Characterization and Biomedical Applications

Injectable Biodegradable Hydrogels

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

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