twelve wistar strain male rats , aged 120 days and with a mean weight of 250 to 300 g , were obtained from the breeding center of the anatomical and biological sciences center , shahid beheshti medical university ( sbmu ) tehran , iran .
the animals were maintained under natural light and humidity conditions ( temperature 22 ; 12-h light / dark cycles ) in individual cages cleaned daily , fed once a day , and offered water ad libitum .
the study was approved by the institutional medical ethics committee of shahid beheshti medical university . on day 0
, the rats were anesthetized by the intramuscular injection of 50 mg / kg ketamine hydrochloride ( rotex , made in germany ) and 5 mg / kg diazepam ( tpico , made in iran ) .
their dorsal hair was shaved , and their skin was cleaned with povidone - iodine .
the rats were equally divided into experimental and control groups randomly ( six rats in each group ) .
four incisional wounds measuring 20 mm in length were made in the dorsolateral regions of each experimental rat and one incisional wound in each control rat .
all the incisions were performed in the skin and subcutaneous cell tissue using a scalpel .
the depth of the surgical incisions was controlled by removing the epithelial tissue to the extent that the dorsal muscular fascia was exposed .
the wounds in the experimental rats were treated with : aloe vera gel ( av ) , thyroid hormone cream ( tc ) , silver sulfadiazine 1% ( s ) , or vehicle ( v ) .
all the therapies were initiated on day 0 and repeated daily for 14 consecutive days .
an aloe vera plant was obtained from a medical plant garden and sent to the laboratory of anatomical and biological sciences center , shahid beheshti medical university ( sbmu ) for the extraction of aloe vera gel .
after washing the leaves thoroughly , the base , apex and margins were cut off carefully to facilitate the slicing of the aloe vera leaves , revealing the transparent mucilage .
a greenish gel - like liquid was obtained which was further refined through the use of a strainer .
we also prepared a topical t3 cream by dissolving 150-ng of t3 ( sigma , made in spain ) in 20 l of ethanol and then mixed it into the vehicle .
the tensile strength of the wounds was measured in both the experimental and control groups on day 14 after surgically inducing the wounds .
we cut standardized 5mm - wide skin strips perpendicularly to the incisions with a double - bladed cutting instrument .
the specimens were placed in 0.9 percent saline after necropsy and were evaluated within one hour . from each wound , we obtained one strip specimen and placed it in a material testing machine ( zwick , made in germany ) using two griping clamps .
the distance between the edges of the clamps was 5 mm and the specimens were loaded uniaxially while the deformation rate was kept constant at 15 mm a minute so that failure and complete load - deformation curves were recorded by transducers coupled to bridges . from these curves , we analyzed the parameters of ( 1 ) ultimate tensile stress ( newtons / square millimeter ) , which was derived from the ultimate load divided by the original unstrained cross - sectional area ; ( 2 ) ultimate tensile strength ( fmax newtons ) , the load that causes a structure to fail ; and ( 3 ) the area under the load - deformation curve ( newton millimeters ) , the amount of work done by the deforming load .
we used a one - way analysis of variance and t tests to compare the data related to ultimate tensile stress , fmax , and area under load - deformation curve .
an aloe vera plant was obtained from a medical plant garden and sent to the laboratory of anatomical and biological sciences center , shahid beheshti medical university ( sbmu ) for the extraction of aloe vera gel .
after washing the leaves thoroughly , the base , apex and margins were cut off carefully to facilitate the slicing of the aloe vera leaves , revealing the transparent mucilage .
a greenish gel - like liquid was obtained which was further refined through the use of a strainer .
we also prepared a topical t3 cream by dissolving 150-ng of t3 ( sigma , made in spain ) in 20 l of ethanol and then mixed it into the vehicle .
the tensile strength of the wounds was measured in both the experimental and control groups on day 14 after surgically inducing the wounds .
we cut standardized 5mm - wide skin strips perpendicularly to the incisions with a double - bladed cutting instrument .
the specimens were placed in 0.9 percent saline after necropsy and were evaluated within one hour . from each wound
, we obtained one strip specimen and placed it in a material testing machine ( zwick , made in germany ) using two griping clamps .
the distance between the edges of the clamps was 5 mm and the specimens were loaded uniaxially while the deformation rate was kept constant at 15 mm a minute so that failure and complete load - deformation curves were recorded by transducers coupled to bridges . from these curves , we analyzed the parameters of ( 1 ) ultimate tensile stress ( newtons / square millimeter ) , which was derived from the ultimate load divided by the original unstrained cross - sectional area ; ( 2 ) ultimate tensile strength ( fmax newtons ) , the load that causes a structure to fail ; and ( 3 ) the area under the load - deformation curve ( newton millimeters ) , the amount of work done by the deforming load .
data were summarised as meansem . we used a one - way analysis of variance and t tests to compare the data related to ultimate tensile stress , fmax , and area under load - deformation curve .
since an increase in the synthesis of collagen occurs in the wound healing process , we used a biomechanical method to examine and compare among the treatments for tensile stress , fmax , and area under load - deformation curve ( table 1 ) .
as table 1 indicates , the tensile stress was not significantly different among tc , av and s. averaged ultimate tensile stress was greater in the av , tc and s groups than in the v and control groups , but this difference was not statistically significant .
no difference in fmax was observed among the tc , s , v , and control groups .
the area under the load - deformation curve was significantly greater in the av group than in the other groups and was not significantly greater in the s and tc groups than in the v and control groups .
skin wound healing is a dynamic response to injury that has three overlapping phases : inflammation , granulation tissue formation and remodeling . during the wound healing process , especially the transition from granulation tissue to scar tissue formation ,
collagen remodeling occurs , that is , the degradation of collagen with the formation of larger collagen bundles and an increase in the number of intermolecular cross - linkages .
this process is controlled by several proteolytic enzymes called matrix metalloproteinases that are discharged by fibroblasts , macroghages , epidermal cells and endothelial cells .
the tensile strength of a wound can be related to its collagen formation and maturation . on the other hand ,
the strength of the repaired wound tissue is the result of the remodeling of collagen and the formation of stable intra - and inter - molecular cross - linkages .
this study examined and compared the effects of aloe vera leaf gel , thyroid hormone cream , and silver sulfadiazine cream on the healing of skin incisional wounds in rats by biomechanical methods to assay the tensile stress of the wounds . according to the results of the study , fmax and the area under the load - deformation curve significantly increased in the wounds treated with aloe vera as compared with the wounds treated with thyroid hormone and silver sulfadiazine , suggesting that aloe vera was more effective in healing the wounds , which has been observed in other studies .
a possible explanation for this increase is that the aloe leaf gel extract infiltrates into the wounds , contributes to the increase of fibroblasts , macrophages , and epidermal cells activities , subsequently facilitates enzyme activity during collagen remodeling , and possibly even aids in the formation of cross linkages as the collagen matures . in other words ,
aloe vera may have a direct effect on the wound healing process as a whole , which is manifested as an increase in fmax and the area under the load - deformation curve , suggesting an improvement in the tensile strength of the wounds .
the results are also in agreement with those of chithra et al . that attributed this improvement in tensile strength to an increase in the aldehyde groups of collagen fibres responsible for forming cross - linkages .
subramanian et al . also confirmed the effect of aloe vera on increasing wound contraction and collagen synthesis and attributed this to the mannose-6-phosphate known to be present in aloe vera leaf gel .
mannose - containing products have been shown to increase macrophage activity and therefore stimulate fibroblast activity and collagen synthesis .
the results indicate that thyroid hormone did not have any significant effect on the healing of the incisional wounds .
thus , the results do not provide evidence for safer et al . who found that topical triiodothyronine stimulated epidermal proliferation , dermal thickening , and hair growth .
one possible explanation for this discrepancy is the difference in the type of wound between the two studies ; in the present study incisional wounds were under investigation while in the other , excisional wounds .
an incision is a cut made into the tissue , mainly for operation , therefore topical medication must infiltrate into the tissue to accelerate the healing process . on the other hand ,
an excision is a removal skin tissue and topical medication is put on the wound directly , which may contribute more to the healing process .
another possible explanation is the difference in the methods of assessing wound healing : safer et al .
used a histological approach to assess whether topical triiodothyronine stimulates epidermal proliferation , dermal thickening , and hair growth while in the present study we drew on a biomechanical assessment method to explain the physical characteristics of the skin tissue .
the findings of the current study indicate that ssd was not significantly effective on skin incisions , providing more evidence for the studies conducted by mccauley et al . and cooper et al . , in that they explained the inhibitory and cytotoxic effects of ssd and mafenide acetate on human keratinocyte and fibroblast growth [ 25 - 28 ] .
leitch et al . also found inhibitory effects of antimicrobial agents on wound contraction in an acute rat wound model .
muller et al . compared the impact of ssd with or without aloe vera , nystatin with and without ssd , and placebo on time to achieve 50% and 90% wound healing in excisions of sprague - dawley rats .
no difference in the acceleration of wound healing was observed between the control and ssd treatment lesions .
in addition , the combination of aloe vera with ssd has been suggested to improve wound healing .
such inhibitory effects may be related to the cytotoxic characteristics of ssd on cells synthesizing collagen , proteoglycan , and other products .
the results of this study indicate that topical application of aloe vera can lead to significantly rapid wound healing and stronger repaired tissue .
we can conclude that aloe vera can effectively be applied as a topical treatment to accelerate the wound healing process of surgically induced incisional wounds in rats as compared with other topical applications such as : thyroid hormone , silver sulfadiazine , and vehicle .
 many research studies report the healing effects of aloe vera , thyroid hormone cream and silver sulfadiazine . 
 however , the effects of these therapeutic agents are not well understood and have not been compared in one study . 
 this study aimed at investigating the effects of topical application of an aloe vera gel , a thyroid hormone cream and a silver sulfadiazine cream on the healing of skin wounds surgically induced in wistar rats for determining the treatment of choice . in a randomized controlled trial , twelve male rats , aged 120 days and with a mean weight of 250 to 300 g , were divided randomly into 5 groups based on drug treatments : aloe vera gel ( av ) , thyroid hormone cream ( tc ) , silver sulfadiazine 1% ( s ) , vehicle ( v ) and control . to evaluate the efficacy of each treatment technique , a biomechanical approach was used to assess tensile stress after 14 days of treatment . 
 tensile stress was significantly improved in the aloe vera gel group as compared with the other four groups ( p0.05 ) . 
 while the other treatment options resulted in better healing than the control group , this difference was not significant . 
 we conclude that aloe vera topical application accelerated the healing process more than thyroid hormone , silver sulfadiazine and vehicle in surgically induced incisions in rats . 
Materials and Methods
Preparation and administration of 
Collection and preparation of wound samples
Data analysis
Results
Discussion