Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats

Shi, Rongfeng; Lian, Weishuai; Han, Shengnan; Cao, Chuanwu; Jin, Yinpeng; Yao, Yuan; Zhao, Hui; Li, Maoquan

doi:10.1038/s41434-018-0027-6

Cited by 51 publications

(37 citation statements)

References 32 publications

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“…Gene therapy for the delivery of growth factors is also in an era of emerging treatment options for wound healing [151]. Shi et al reported a combined gene transfer of VEGF-A and PDGF-B for diabetic foot ulcers in rats [152]. The aim of the study was to analyze whether the engineered growth factors based plasmid-loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats and improve the wound healing.…”

Section: Reviewmentioning

confidence: 99%

Advances in surgical applications of growth factors for wound healing

2019

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Growth factors have recently gained clinical importance for wound management. Application of recombinant growth factors has been shown to mimic cell migration, proliferation, and differentiation in vivo, allowing for external modulation of the healing process. Perioperative drug delivery systems can enhance the biological activity of these growth factors, which have a very short in vivo half-life after topical administration. Although the basic mechanisms of these growth factors are well understood, most have yet to demonstrate a significant impact in animal studies or small-sized clinical trials. In this review, we emphasized currently approved growth factor therapies, including a sustained release system for growth factors, emerging therapies, and future research possibilities combined with surgical procedures. Approaches seeking to understand wound healing at a systemic level are currently ongoing. However, further research and consideration in surgery will be needed to provide definitive confirmation of the efficacy of growth factor therapies for intractable wounds.

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Section: Reviewmentioning

confidence: 99%

Advances in surgical applications of growth factors for wound healing

2019

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“…The rats were allowed to develop diabetes for 4 weeks. 18 At 3, 6 or 8 weeks after feeding and 4 weeks after STZ injection, the body weight was recorded for all the rats.…”

Section: Induction Of Diabetesmentioning

confidence: 99%

“…After randomization, the animals were anesthetized with thiopental sodium (50 mg/kg) and a full thickness foot ulcer was made on dorsal hind foot by using Westcott scissor and 6 mm punch biopsy. 18…”

Section: Creation Of Diabetic Foot Ulcermentioning

confidence: 99%

<p>Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats</p>

Gourishetti¹,

Keni²,

Nayak³

et al. 2020

IJN

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Background: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, antihyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. Methods: Sesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound reepithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. Results: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. Conclusion: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.

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“…1 Diabetic foot ulceration (DFU), a severe complication of DM, could dramatically influence the life quality of patients and could even be life-threatening. 2 Chronic wounds induced by diabetic foot are physiological impairments characterized by deferments in healing, which will lead to severe morbidity and mortality. 3 More than 80% of foot ulcers may end up with lower extremity diabetic amputations, thus promoting the wound healing of ulcers and preventing recurrence of ulceration becoming a major focus in preventing amputation.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

Zhou

Chen

et al. 2020

FASEB j.

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Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)-29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM-related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR-29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR-29b and FBN1. According to microarray-based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR-29b were observed. FBN1 was identified to be a target gene of miR-29b. LncRNA H19 could competitively bind to miR-29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR-29b, which diminished the expression of TGF-β1, Smad3, FN, and Col-1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR-29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.

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Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats

Cited by 51 publications

References 32 publications

Advances in surgical applications of growth factors for wound healing

Advances in surgical applications of growth factors for wound healing

<p>Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats</p>

Long noncoding RNA H19 acts as a miR‐29b sponge to promote wound healing in diabetic foot ulcer

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