Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds

被引:136
|
作者
Koria, Piyush [1 ,2 ,3 ,4 ]
Yagi, Hiroshi [1 ,2 ,3 ,5 ]
Kitagawa, Yuko [5 ]
Megeed, Zaki [1 ,2 ,3 ]
Nahmias, Yaakov [1 ,2 ,3 ,6 ]
Sheridan, Robert [1 ,2 ,3 ]
Yarmush, Martin L. [1 ,2 ,3 ,7 ]
机构
[1] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02129 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Shriners Hosp Children, Boston, MA 02114 USA
[4] Univ S Florida, Dept Chem & Biomed Engn, Tampa, FL 33620 USA
[5] Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan
[6] Hebrew Univ Jerusalem, Selim & Rachel Benin Sch Engn, IL-91904 Jerusalem, Israel
[7] Rutgers State Univ, Piscataway, NJ 08854 USA
关键词
skin; fusion peptides; regeneration; PROTEIN-BASED POLYMERS; FACTOR EXPRESSION; COLLAGEN SPONGE; DIABETIC MOUSE; KGF RECEPTOR; POLYPEPTIDE; FIBROBLASTS; INDUCTION; MODEL; DIFFERENTIATION;
D O I
10.1073/pnas.1009881108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Chronic wounds are associated with poor epidermal and dermal remodeling. Previous work has shown the efficacy of keratinocyte growth factor (KGF) in reepithelialization and elastin in dermal wound healing. Here we demonstrate the fabrication of a fusion protein comprising of elastin-like peptides and KGF. This fusion protein retains the performance characteristics of KGF and elastin as evidenced by its enhancement of keratinocyte and fibroblast proliferation. It also preserved the characteristic elastin-like peptides inverse phase transitioning allowing the recombinant protein to be expressed in bacterial hosts (such as Escherichia coli) and purified rapidly and easily using inverse temperature cycling. The fusion protein self-assembled into nanoparticles at physiological temperatures. When applied to full thickness, wounds in Lepr(db) diabetic mice these particles enhanced reepithelialization and granulation, by 2- and 3-fold respectively, when compared to the controls. The data strongly suggests that these self-assembled nanoparticles may be beneficial in the treatment of chronic wounds resulting from diabetes or other underlying circulatory conditions.
引用
收藏
页码:1034 / 1039
页数:6
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