Mitomycin C-polyethylene glycol controlled-release film inhibits collagen secretion and induces apoptosis of fibroblasts in the early wound of a postlaminectomy rat model.
BACKGROUND
Recovery from spine surgery is usually accompanied with the development of epidural scar adhesions from the abnormal proliferation of fibroblast and extracellular matrix-related metabolism. Polyethylene glycol (PEG) could alleviate the postsurgical adhesion formation with still leaving a gap between the sheet and the dura. However, PEG film could not function as a three-dimensional barrier to prevent adhesion completely. Mitomycin C (MMC) could also reduce the scar formation after surgery, but cytotoxicity and the administrative pathway prevent its application.


OBJECTIVE
Our purpose was to design and attest the role of new delivery system MMC-PEG controlled-release film in preventing the epidural scar adhesions after laminectomy in the rat model.


METHODS
A total laminectomy of L1 in the rat model was used to assess epidural fibrosis between and around the spinal nerves using a histochemistry assessment along with flow cytometry analysis.


METHODS
The sample comprises 64 adult male Sprague-Dawley rats.


METHODS
The outcome measures are macroscopic evaluation, histological analysis, and flow cytometry analysis.


METHODS
Lumbar laminectomies at L1 and L2 with a L1-L2 disc injury were performed on 64 adult male Sprague-Dawley rats. The rats were then randomized into four groups. In Group I, 25 mg PEG film was applied on the dura mater in the laminectomy area before the layers were sutured. In Group II, a cotton pad soaked with 0.05% MMC solution was kept on the laminectomy area for 5 minutes. In Group III, 25 mg PEG film containing 0.01% MMC was implanted on the laminectomy area. In Group IV, the laminectomy area was flushed with saline before wound closure. The rats were sacrificed 4 weeks after the operation. Macroscopic evaluation and histological analysis of epidural scar adhesion with the hematoxylin and eosin stain and Masson stain were used followed by the quantification of hydroxyproline (Hyp) and flow cytometry analysis of the apoptosis of fibroblasts in the scar tissues.


RESULTS
The recovery of all rats was uneventful after the operations. In the laminectomy sites of rats treated with MMC or MMC-PEG, the dura mater was clean without any evident adhesion or membrane. Collagen tissue hyperplasia significantly decreased in the MMC- or MMC-PEG-treated models. Accordingly, Hyp concentration was significantly reduced in these two groups compared with saline-control group. In addition, the apoptosis of fibroblasts, however, was significantly elevated in the MMC or MMC-PEG group compared with the saline-control group.


CONCLUSIONS
These results demonstrate that the treatment of postlaminectomy wounds with MMC-PEG film reduces the severity of adhesion by decreasing the concentration of Hyp and increasing the apoptosis of fibroblasts.
Liu
Jun
J
Department of Orthopedics, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai 200003, People's Republic of China.
Ni
Bin
B
Zhu
Liang
L
Yang
Jun
J
Cao
Xiaojian
X
Zhou
Wei
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002921:Cicatrix / Q000517:prevention & control; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004388:Dura Mater / Q000473:pathology; D004824:Epidural Space / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D007796:Laminectomy; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D016685:Mitomycin / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control
D003692:Delayed-Action Preparations; D011092:Polyethylene Glycols; D016685:Mitomycin; D003094:Collagen