The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin

Choi, Jin Kyu; Jang, Ji Hye; Jang, Won Hee; Kim, Jae-Kwan; Bae, Il-Hong; Bae, Jin Woo; Park, Young Ho; Kim, Beum Joon; Lim, Kyung Min; Park, Jin Woo

doi:10.1016/j.biomaterials.2012.07.061

Cited by 89 publications

(71 citation statements)

References 43 publications

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“…Although it showed a significantly higher rate of healing versus free-EGF treatment, outstanding efficacy was seen only in the early stages of wound healing. 27 This may have been caused by the normal progression of matrix synthesis and deposition and remodeling in the dermal layer of the wound bed, which ultimately resulted in no difference …”

Section: Discussionmentioning

confidence: 99%

“…27,28 rLMWP-IGF-I and rLMWP-PDGF-A were also prepared with an expression plasmid, which overproduced a protein containing rLMWP-IGF-I and LMWP-PDGF-A in Escherichia coli in a similar manner to rLMWP-EGF. Briefly, as the first template, complementary (c)DNAs for rLMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A were constructed by serial polymerase chain reaction (PCR)-mediated addition of the LMWP codons to the rhEGF, rhIGF-I, and rhPDGF-A genes (GenBank accession numbers P01133, P03143, and NP-008808.3, respectively).…”

Section: Preparation Of Lmwp-conjugated Growth Factorsmentioning

confidence: 99%

“…27,28 In the present study, we constructed a topical formulation consisting of highly skin-permeable recombinant growth factors and low-molecular-weight heparin (LMWH) nanocomplexes, for multitargeted wound-healing efficacy. To maintain the native biological properties of the growth factors as well as to increase their skin permeability, we fused the cell-penetrating peptide LMWP with the N-terminus of EGF, IGF-I, and PDGF A ligand (PDGF-A) (producing recombinant [r]LMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A, respectively) via genetic modification.…”

mentioning

confidence: 99%

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Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

Bae¹,

Park²,

Kim³

2014

IJN

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Exogenous administration of growth factors has potential benefits in wound healing; however, limited percutaneous absorption, inconsistent efficacy, and the need for high doses have hampered successful clinical use. To overcome these restrictions, we focused on the development of a topical formulation composed of highly skin-permeable multimeric nanocomplex of growth factors. In the present study, we fused low-molecular-weight protamine (LMWP) with epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-I), and platelet-derived growth factor A ligand (PDGF-A) (producing recombinant [r]LMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A, respectively) via genetic modification. Then, we used in vitro cell proliferation studies to assess the biological activity and the benefits of the combination. The LMWP-conjugated growth factors were complexed with low-molecular-weight heparin (LMWH) and formulated with Poloxamer 188 as a delivery vehicle. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether the LMWP-conjugated growth factor nanocomplex formulations accelerated the healing of full-thickness wounds in mice. The LMWP-conjugated growth factors were biologically equivalent to their native forms, and their combination induced greater fibroblast proliferation. rLMWP-EGF showed significantly enhanced permeability and cumulative permeation, and the rates for rLMWP-IGF-I and rLMWP-PDGF-A, across excised mouse skin, were 124% and 164% higher, respectively, than for the native forms. The LMWP-fused growth factors resulted in formation of nanocomplexes (23.51±1.12 nm in diameter) in combination with LMWH. Topical delivery of growth factors fused with LMWP accelerated wound re-epithelialization significantly, accompanied by the formation of healthy granulation tissue within 9 days compared with a free–growth factor complex or vehicle. Thus, the LMWP-conjugated growth factor nanocomplex can induce rapid, comprehensive healing and may be a candidate wound-healing therapeutic.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Lmwp-conjugated Growth Factorsmentioning

confidence: 99%

mentioning

confidence: 99%

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Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

Bae¹,

Park²,

Kim³

2014

IJN

Self Cite

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“…Therefore, provision of exogenous growth factors at precisely timed intervals would provide stimulation to induce faster reepithelialization, as well as reduce the risk of infection. [8][9][10] Unfortunately, the therapeutic use of growth factors is limited since they can be easily degraded by proteinases or removed by exudate before reaching the wound bed. Few growth factors, except PDGF-BB, have successfully completed clinical trials.…”

Section: Introductionmentioning

confidence: 99%

EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

et al. 2016

IJN

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Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair.

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“…Among numerous growth factors applied in the clinic, epidermal growth factor (EGF) is the first and foremost factor to promote the wound healing (11,12). EGF possesses high-affinity receptors that are expressed by both fibroblasts and keratinocytes, and improves epidermal and mesenchymal regeneration, cell mobility, proliferation and synthesis of the ECM, then consequently facilitate wound healing (13,14). To preserve EGF bioactivity, and also to protect the tissue in the reconstruction phase, an efficient approach could be embedded EGF into a suitable dressing, which provides the capability for sustained release of EGF when applied on top of the wound (13,14).…”

Section: Introductionmentioning

confidence: 99%

Preparation and properties of a novel carbon nanotubes/poly(vinyl alcohol)/epidermal growth factor composite biological dressing

Liao

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Wound dressings with drug delivery system have drawn increasing attention in skin damage recombination. Herein, a novel composite biological dressing was prepared and based on poly(vinyl alcohol) (PVA) combined with carbon nanotubes (CNTs) and epidermal growth factor (EGF) by electrospinning on gauze. The properties of the CNTs/PVA/EGF composite dressing were systemically investigated by general observation, and scanning electron microscopy (SEM). In vitro, the cytotoxicity of this dressing was investigated using a methyl thiazolyl tetrazolium (MTT) assay on L929 fibroblasts. In order to study the sustained release of EGF from this dressing, the concentration of EGF at different times was tested by ELISA. Furthermore, the biological activity of the released EGF was also evaluated using the MTT assay. Moreover, an in vivo experiment was conducted to observe whether this dressing was capable of improving healing in the model of wounded skin on rats. It was revealed that this dressing had a well-distributed microstructure by SEM. Additionally, the grade of cytotoxicity was low, and the EGF had a sustained release rate from this dressing. Furthermore, a maximum accumulative release rate of 12.47% was identified at 12 h, and was retained at 9.4% after 48 h. Simultaneously, the relative growth rate of L929 fibroblasts in the 12 h experimental group and 48 h group was 291.24 and 211.3%, respectively. Next, the efficacy of these products was evaluated in vivo using Sprague-Dawley rats with a skin injury model. The healing of wounded skin of rats was sped up by this dressing based on the gross and histological appearances. From 7 to 10 days, the wounds in the experimental group were almost healed. In conclusion, this CNTs/PVA/EGF dressing had a well-distributed structure and an ability to release EGF at a sustained rate with the activity being favorable. On the basis of those results, a positive influence of designed dressing for accelerated wound healing was confirmed.

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The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin

Cited by 89 publications

References 43 publications

Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent

Preparation and properties of a novel carbon nanotubes/poly(vinyl alcohol)/epidermal growth factor composite biological dressing

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