Effect of PLGA scaffold incorporating VEGF and bFGF loaded nanoparticles on wound healing in case of radiation injury
WANG Mu1, ZENG Yong2, ZHANG Lei2, YANG Yan3, GAO Mingmin1
1.Department of Plastic Surgery, 2. Department of Burn Surgery, 3. Department of General Surgery, Shanghai Municipal Corps Hospital, Chinese People’s Armed Police Force, Shanghai 201103,China
Abstract:Objective To study the effects of poly lactic-co-glycolic acid(PLGA) scaffold incorporating VEGF and bFGF loaded nanoparticle complexes on the healing of murine radioactive wounds.Methods Mice undergoing combined application of PLGA and VEGF/bFGF loaded nanoparticle complexes against radioactive wounds were assigned to the experimental group, while those among whom PLGA alone was used to treat radioactive wounds were considered the control group. The wound healing rate and pathological changes of the wounds were observed, while the number of new vascular cells, the area of capillary interception and the number of fibroblasts were detected at different time points after injury between the two groups.Results With regard to the wound surface of mice with radiation injury, the wound healing rate of the experimental group was significantly higher than that of the control group after the combined application of bFGF and VEGF. The expressions of VEGF mRNA and bFGF mRNA in wound tissue of the experimental group were higher than those of the control group, and there was significant difference between the two groups (P<0.05). HE staining performed on the wound tissue suggested that the granulation tissue in the experimental group increased and thickened, and the number and density of fibroblasts were better than those of the control group. Eight and fifteen days after injury, the number and the cross-sectional area of newborn blood capillaries were both increased in the experimental group compared with the control group, so was the number of fibroblasts.Conclusions PLGA nanoparticle complexes loaded with VEGF and bFGF can promote the healing of radioactive wounds in mice.
Olascoaga A, Vilar C D, Poitevin C A, et al. Wound healing in radiated skin: pathophysiology and trend opinions [J]. Int Wound, 2008, 5:246-257
[3]
Jia J, Dellinger A E,Weiss E S,et al. Direct evidence of target inhibition with Anti-VEGF, EGFR, and mTOR therapies in a clinical model of wound healing [J]. Clin Cancer Res,2015, 21 (15): 3442-3452.
[4]
Li W, Lan Y,Guo R,et al. In vitro and in vivo evaluation of a novel collagen/cellulose nanocrystals scaffold for achieving the sustained release of basic fibroblast growth factor [J]. Biomater Appl,2015,29(6):882-893.
[5]
Shen T,Pan Z G,Zhou X,et al. Accelerated healing of diabetic wound using artificial dermis constructed with adipose stem cells and poly (L-glutamic acid)/chitosan scaffold [J]. Chin Med (Engl),2013,126(8):1498-1503.
Johnson K E, Wilgus T A. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair [J]. Adv Wound Care,2014,3(10):647-661.
[8]
Gilliver S C,Emmerson E,Bernhagen J,et al. MIF: a key palyer in cutaneous biology and wound healing [J]. Exp Dermatol,2011,20(1):1-6.
[9]
Schultz G S, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing [J]. Wound Repair Regen, 2009, 17(2):153-162.
[10]
Sivamani R K, Garcia M S, Isseroff R R. Wound re-epithelialization:modulating keratinocyte migration in wound healing [J]. Front Biosci,2007,12:2849-2868.
[11]
Eming S A,Smola H, Krieg T. Treatment of chronic wounds: state of the art and future concepts [J]. Cells Tissues Organs, 2002,172(2):105-117.
[12]
Lauer G,Sollberg S,Cole M,et al. Expression and proteolysis of vascular endothelial growth factor is increased in chronic wounds[J]. Invest Dermatol,2000,115(1):12-18.
[13]
Galiano R D, Tepper O M, Pelo C R, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells [J]. Am J Pathol, 2004, 164(6): 1935-1947.
[14]
Soscia D A, Raof N A, Xie Yubing, et al. Antibiotic-Loaded PLGA nanofibers for wound healing applications [J]. Adv Engineering Materials,2010,12(4):83-88.
[15]
Kim I S,Lee S K, Park Y M,et al. Physicochemical characterization of poly(L-lactic acid) and poly(D,L-lactide-co-glycolide) nanoparticles with polyethylenimine as gene delivery carrier [J]. Int J Pharm,2005,298(1):255-262.
[16]
Cui F Y,Song X R,Li Z Y,et al. The pigment epithelial-derived factor gene loaded in PLGA nanoparticles for therapy of colon carcinoma [J]. Oncol Rep, 2010,24(3):661-618.
[17]
Barrientos S,Stojadinovic O,Golinko M S,et al. Growth factors and cytokines in wound healing [J]. Wound Repair Regen,2008,16(5):585-601.
[18]
Chen J,De S,Brainard J, et al. Metastatic properties of prostate cancer cells are controlled by VEGF [J]. Cell Commun Adhes,2004,11(1):1-11.
[19]
Takamiya M,Saigusa K,Nakayashiki N,et al. Studies on mRNA expression of basic fibroblast growth factor in wound healing for wound age determination [J]. Int J Legal Med,2003,117(1):46.