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Acceleration of diabetic‐wound healing with PEG ylated rhaFGF in healing‐impaired streptozocin diabetic rats
Author(s) -
Huang Zhifeng,
Lu Meifei,
Zhu Guanghui,
Gao Hongchang,
Xie Liyun,
Zhang Xiaoqin,
Ye Chaohui,
Wang Yan,
Sun Chuanchuan,
Li Xiaokun
Publication year - 2011
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2011.00722.x
Subject(s) - pegylation , in vivo , wound healing , pharmacology , chemistry , polyethylene glycol , peg ratio , biochemistry , medicine , immunology , biology , microbiology and biotechnology , finance , economics
Molecular modification with polyethylene glycol ( PEG ylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor ( rhaFGF ) was site‐selectively PEG ylated with 20 k D a m PEG ‐butyraldehyde. M ono‐ PEG ylated rhaFGF was purified to near homogeneity by S ephadex G 25‐gel filtration followed by a H eparin S epharose TM CL ‐6 B affinity chromatography. PEG ylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half‐life time in vivo was significantly extended. Then, the physiological function of PEG ylated rhaFGF on diabetic‐wound healing was evaluated in type 1 diabetic S prague D awley rats. The results showed that, compared with the group of animal treated with native rhaFGF , the group treated with PEG ylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor ( TGF )‐β expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEG ylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEG ylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF .