Healing In Rabbits Research Articles

Evaluation of Possible Beneficial Effect of Tricalcium Phosphate/Collagen (TCP/collagen) Nanocomposite Scaffold on Bone Healing in Rabbits: Biochemical Assessments

Objective- The aim of this study was to evaluate possible beneficial effect of tricalcium phosphate/collagen (TCP/collagene) nanocomposite scaffold on bone healing in rabbits using biochemical assessmentsDesign- Experimental studyAnimals- Twelve healthy male white New Zealand rabbitsProcedures- The rabbits were marked with non-toxic color and randomly divided into two groups of 6 animals each. In the first group (SHAM) the defect was made and with no treatment the wound was closed. In the second group (TCP/C) the tricalcium phosphate/collagen (TCP/collagene) nanocomposite scaffold was implanted into the defect. Before the procedures (day 0) and on 7, 15, 30, 45 and 60 postoperative days the blood samples were taken from jugular vein and undergone hematological and biochemical assessments.Results- The hematological, biochemical and oxidative stress parameters including WBC, RBC, HCT, PLT, neutrophil, lymphocytes, BUN, Creatinine, AST, ALT, ALP, SOD, GPX and MDA showed statistically significant differences between Sham and TCP/C groups (p<0.05). Conclusion and clinical relevance- It was concluded that TCP/collagen nanocomposite improved the biochemical parameters in the nanocomposite treated animals and could be of clinical benefit in reconstruction of bone defects and could be considered as a scaffold in bone fractures.

The Use of Platelet-Rich Plasma and Rosuvastatin in Wound Healing in Rabbits: A Longitudinal Study.

To test the hypothesis that platelet-rich plasma (PRP) improves wound healing in rabbits by analyzing morphologic alterations in lesions with the use of PRP alone or combined with rosuvastatin (RSV). Eight adult male New Zealand rabbits were used in this study. Researchers created four wounds on the back of each rabbit with an 8-mm punch. The control wound was treated with a 0.9% sodium chloride solution. Experimental wounds were treated with PRP, RSV, or both PRP and RSV. Dressings were changed with a new application of PRP and RSV every 4 days for 16 days. Wounds were biopsied on days 0, 7, 10, 14, and 17 for histopathologic evaluation of the scar tissue. Histopathology revealed reepithelialization in 100% of wounds treated with PRP alone after 17 days of treatment, compared with 50% of wounds treated with RSV alone and 75% of the wounds treated with PRP and RSV. Further, combining RSV and PRP reduced blood loss. The use of PRP alone induced 100% neovascularization, compared with 50% and 62.5% in wounds treated with PRP and RSV and RSV alone, respectively. All experimental wounds had a higher percentage of collagen fibers on day 17 postlesion when compared with control wounds (78.27% ± 4.69%). There were no significant differences among treatments; however, wounds treated with RSV alone had the lowest amount of collagen fibers (85.98% ± 3.51%). Wounds treated with PRP alone or PRP and RSV had 90.07% ± 6.20% and 90.76% ± 3.51% collagen fibers, respectively. The results of this study indicate that PRP elicits higher healing activity in the first 7 days postlesion. Treatments with RSV alone or RSV and PRP did enhance other healing phases.

Histological and antimicrobial effects of tramadol infiltration on incisional oral mucosal wound healing in rabbits

Histological and antimicrobial effects of tramadol infiltration on incisional oral mucosal wound healing in rabbits

Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits

BackgroundVarious extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits.MethodsAsiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model.ResultsThe results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits’ skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected.ConclusionThe asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

Low-expression of lncRNA-ANCR promotes tibial fracture healing via targeting RUNX2.

To explore the role of long non-coding ribonucleic acid-anti-differentiation non-coding ribonucleic acid (lncRNA-ANCR) in tibial fracture healing in rabbits by regulating the runt-related transcription factor 2 (RUNX2) expression. A total of 60 healthy adult rabbits were evenly divided into Control group (n=20), Fracture group (n=20), and Lnc group (n=20). Then, RUNX2 transfection, Real Time Polymerase Chain Reaction (PCR) assay and relevant instruments were carried out and used to determine the differences in dry weight, bone mineral density, bone mechanical strength, and RUNX2 expression in tibiae among three groups of rabbits. Comparison of the bone mineral density in rabbit tibiae among the three groups showed that the bone mineral density was significantly lower in Fracture group than that in Control group (p<0.05), and it was slightly higher in Lnc group than in Fracture group (p<0.05). The dry weight of the full-length tibiae in Fracture group was significantly decreased compared with that in Control group (p<0.05), and Lnc group had an increased dry weight of tibiae in comparison with Fracture group (p<0.05). The maximum load, flexural strength, elastic stress, elastic strain, elastic modulus, maximum stress, and maximum strain in Fracture group were lower than those in both Control group and Lnc group (p<0.05). Compared with those in Fracture group, the amount of new collagen was overtly increased in Lnc group, and that of mature collagen was decreased (p<0.05). The relative expression level of RUNX2 in tibial bone tissues was evidently lower in Fracture group than that in Control group (p<0.05), and it was markedly higher in Lnc group than that in Fracture group (p<0.05). Down-regulating lncRNA-ANCR activates and triggers the expression of RUNX2 that facilitates the growth and metabolism of bone tissues to play an important role in the repair of bone tissues and promote the healing of the tibial fracture.

Comparison and Evaluation of the Low-Level Laser and the Red and Blue LED Effects on Wound Healing in Rabbit.

Introduction: Wound healing is a dynamic, interactive process to achieve the restoration of skin integrity and proper function after damage. Applying a low-level laser (LLL) and light emitting diodes (henceforth LEDs) is introduced in previous studies to accelerate the process of wound healing. The aim of this study is to compare the effect of the LLL and LEDs on wound healing in rabbits. Methods: Full thickness same size square excision wounds were created on the dorsum of the rabbits. Twenty rabbits were randomly divided into four groups, according to the treatment received. Group 1: the AlGalInP (aluminium gallium indium phosphide) laser (4 J/cm²); group 2: the red LED (30 J/cm²); group 3: the blue LED (60 J/cm²) and group 4, as the control group, was not irradiated. After 30 days, the wounds were evaluated both morphologically and histopathologically. Statistical significance was defined as a P value of less than 0.05. Results: All interfering methods including the LLL and LEDs had better outcome compared with the control group of both sizes and histopathologic features. The red laser group showed better results compared to the control group and either the LED groups. Comparing LEDs, the red LED performed better than the blue LED. Conclusion: This study confirmed the significant effects of the LLL and LEDs on wound healing. Comparing the LLL and LED, the LED may be a better choice, especially for bedridden or debilitated patients. The LED may also more cost effective in wound healing in comparison with the LLL.

The activity of serratiopeptidase on oral wound healing in rabbits

The activity of serratiopeptidase on oral wound healing in rabbits

Is sex a biological variable in corneal wound healing?

Wound healing differs significantly between men and women in a tissue-dependent manner. Dermal wounds heal faster in women whereas mucosal wounds heal faster in men. However, the effect of sex as a variable in corneal wound healing is largely unknown. The primary objective of this study was to test whether sex is a biological variable in corneal wound healing activated by the trauma or injury using an established in vivo rabbit model with male and female New Zealand White rabbits. Corneal wounds in rabbits were produced by a single topical alkali (0.5N Sodium hydroxide) application. Serial slit-lamp, stereo biomicroscopy, and applanation tonometry evaluated corneal opacity, anterior segment ocular health, and intraocular pressure (IOP), respectively, at various times during the study. Fourteen days after alkali-wound, corneal tissues were collected after humane euthanasia to examine cellular and molecular wound healing parameters. Quantitative PCR (qPCR) and immunofluorescence were used to quantify changes in the extracellular modeling protein levels of alpha-smooth muscle actin (α-SMA), Fibronectin (FN), Collagen-I (Col-I), and Transforming growth factor beta 1 (TGFβ1) involved in corneal healing. Hematoxylin and Eosin (H&E) staining was used to study histopathological changes in morphology and TUNEL assay to evaluate levels of apoptotic cell death. Male and female rabbits showed no significant differences in corneal opacity (Fantes score) or intraocular pressure (IOP) values (9.5 ± 0.5 mm Hg) in live animals. Likewise, no statistically significant sex-based differences in the mRNA levels of α-SMA (male = 5.95 ± 0.21 fold vs. female = 5.32 ± 0.043), FN (male = 3.02 ± 0.24 fold vs. female = 3.23 ± 0.27), Col-I (male = 3.12 ± 0.37 fold vs. female = 3.31 ± 0.24), TGFβ1 (male = 1.65 ± 0.06 fold vs. female = 1.59 ± 0.053); and protein levels of α-SMA (male = 74.16 ± 4.6 vs. female = 71.58 ± 7.1), FN (male = 60.11 ± 4.6 vs. female = 57.41 ± 8.3), Col-I (male = 84.11 ± 2.8 vs. female = 84.55 ± 3.6), TGFβ1 (male = 11.61 ± 2.8 vs. female = 9.5 ± 3.04) were observed. Furthermore, H&E and TUNEL analyses found no statistically significant differences in cellular structures and apoptosis, respectively, in male vs. female corneas. Consistent with earlier reports, wounded corneas showed significantly increased levels of these parameters compared to the unwounded corneas. Our data suggest that sex is not a major biological variable during active early stages of corneal wound healing in rabbits in vivo.

LncRNA KCNQ1OT1 delayed fracture healing through the Wnt/β-catenin pathway.

The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) on fracture healing and its possible mechanism. Abnormal lncRNAs were compared between patients with delayed fracture healing and those with normal fracture healing using gene expression profiling method. LncRNA expression in patients was verified by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Subsequently, the model of tibial fracture was successfully established in rabbits. The effect of lncRNA KCNQ1OT1 expression on tibial fracture healing in rabbits was explored. Meanwhile, the effects of lncRNA KCNQ1OT1 on cell proliferation and apoptosis were investigated by knockdown and overexpression experiments with HC-a as a cell model. Furthermore, Western blotting was used to explore the expressions of proteins in signaling pathway affected by lncRNA KCNQ1OT1. Gene expression profiling and qRT-PCR revealed that lncRNA KCNQ1OT1 was significantly down-regulated in bone tissues of patients with delayed fracture healing. Compared with the control group, knocking down lncRNA KCNQ1OT1 remarkably reduced the serum levels of alkaline phosphatase (ALP) and osteoprotegerin (OPG) in rabbits, and markedly decreased bone trabecular growth index (p<0.05). In HC-a cells, overexpression of lncRNA KCNQ1OT1 activated the Wnt/β-catenin signaling pathway, which could be suppressed by knocking down lncRNA KCNQ1OT1. Cell Counting Kit-8 (CCK-8) assay and 5(6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE) results manifested that lncRNA KCNQ1OT1 remarkably promoted the proliferation and inhibited apoptosis of HC-a cells by activating the Wnt/β-catenin signaling pathway. LncRNA KCNQ1OT1 plays a vital role in delayed fracture healing. Moreover, it can induce cell proliferation and inhibit cell apoptosis by activating the Wnt/β-catenin signaling pathway. Therefore, KCNQ1OT1 may be used as a biomarker to predict the occurrence of delayed fracture healing.

Lesão do tendão flexor: sutura na região avascular ou vascularizada? Estudo biomecânico e histopatológico em coelhos

Objectives The present study aims to analyze the mechanical and histopathological aspects of flexor tendon healing focusing on the suture placement site in a vascular or in an avascular region. Methods A total of 83 rabbits were submitted to a Kessler-type central suture in the vascularized tendon region (TN group) and in the avascular tendon region (FC group). The operated limb was immobilized for 3 weeks. The animals were sacrificed in the immediate postoperative period, and at 2, 3 and 6 weeks after the procedure. The mechanical properties studied were: maximum load, stress at maximum load, modulus of elasticity, energy at maximum load, and energy per area. The contralateral tendon was used as control. The histopathological study was descriptive. Results The analysis of the mechanical properties showed similar behavior in both groups, with stabilization or discrete increased values between the immediate period and 3 weeks after the procedure, and marked increased values at 6 weeks. Histopathology demonstrated that the healing process was similar in the TN and FC groups. Conclusion Central suture placement in the vascularized or avascular fibrocartilaginous region results in no differences in the biomechanical and histopathological aspects of flexor tendon healing in rabbits.

The effects of luteolin nanoparticles on the healing of extracted tooth socket in rabbits

Objective: To evaluate the effects of luteolin nanoparticles on the process tooth socket healing in rabbits. Design: This study comprised five rabbits randomly assigned to control animal and experimental animals. Immediately after the extraction of an upper maxillary incisor, the alveolar sockets of experimental animals were treated with topical luteolin while alveolar sockets of the control group remained without treatment. The animals were sacrificed by decapitation with deep anesthesia seven days post tooth extraction. The tooth sockets were sectioned and stained with hematoxylin and eosin stains. Results: Histological evaluation revealed that luteolin treatment induced earlier healing of extracted tooth sockets. Conclusion: These findings suggest that luteolin accelerates the healing process in tooth sockets of rabbits.

Efektifitas Lumatan Daun Jambu Biji (Psidium guajava linn) Terhadap Penyembuhan Luka Bakar (Vulnus combustion) Pada Kelinci

Guava (Guava guajava linn) or guava contains high pectin so it can lower cholesterol, contain tannins that serves to improve the digestive system. Chemical compounds contained in the fruit guava echoes its shape is quersetin i.e. the type of flavonoid compounds a flavonol, flavones, and flavol, which helps them were to treat the fragility of capillaries in the human. The purpose of this research is to know the effectiveness of guava leaf lumatan (Guava guajava linn) in burn healing in rabbits. The methods used in this study was an experimental method using a control group, the Group and the comparison group test (perlakuaan). The results showed that of the negative control group provides the longest healing impact i.e. on the 13th, the positive control healing burns on day 8, and control using lumatan guava leaf healing burns on day 9 control group comparison, bioplacenton indicates days of healing Burns most rapidly healed. &#x0D;

Comparison of Single Versus Multiple Low-Level Laser Applications on Bone Formation in Extraction Socket Healing in Rabbits (Histologic and Histomorphometric Study)

This study evaluated the effect of low-level laser therapy (LLLT) on bone healing after tooth extraction in healthy rabbits and compared the effect between single and multiple doses of laser therapy. Thirty-six New Zealand white male rabbits were randomly divided into 3 equal groups: a control (C) group, a single laser (SL) group, and a multiple laser (ML) group. The mandibular right first premolar was extracted. The SL group received a single dose of diode laser immediately after extraction. The ML group received a dose immediately after extraction and then every 72hours for 12days. The Cgroup extraction sites were left untreated by laser. Eighteen animals were sacrificed at each of the experimental periods 3 and 6weeks after extraction. The sockets were removed from the harvested mandibles and prepared for light microscopic examination and histomorphometric analysis. The SL and ML groups showed more bone formation and rapid maturation compared with the Cgroup at 3 and 6weeks postoperatively. At 6weeks, the SL group showed the formation of compact bone. Furthermore, the ML group exhibited well-vascularized bone marrow spaces. Histomorphometric analysis showed an increase in the percentage of newly formed bone in the SL and ML groups compared with the C group. Moreover, the difference in the percentage of newly formed between the SL and ML groups was not statistically relevant. This rabbit model showed that single or multiple diode laser applications can be used to enhance bone formation after tooth extraction.

Combined plasma rich in growth factors and adipose-derived mesenchymal stem cells promotes the cutaneous wound healing in rabbits

BackgroundThe use of Plasma Rich in Growth Factors (PRGF) and Adipose Derived Mesenchymal Stem Cells (ASCs) are today extensively studied in the field of regenerative medicine. In recent years, human and veterinary medicine prefer to avoid using traumatic techniques and choose low or non-invasive procedures. The objective of this study was to evaluate the efficacy of PRGF, ASCs and the combination of both in wound healing of full-thickness skin defects in rabbits. With this purpose, a total of 144 rabbits were used for this study. The animals were divided in three study groups of 48 rabbits each depending on the administered treatment: PRGF, ASCs, and PGRF+ASCs. Two wounds of 8 mm of diameter and separated from each other by 20 mm were created on the back of each rabbit: the first was treated with saline solution, and the second with the treatment assigned for each group. Macroscopic and microscopic evolution of wounds was assessed at 1, 2, 3, 5, 7 and 10 days post-surgery. With this aim, 8 animals from each treatment group and at each study time were euthanized to collect wounds for histopathological study.ResultsWounds treated with PRGF, ASCs and PRGF+ASCs showed significant higher wound healing and epithelialization rates, more natural aesthetic appearance, significant lower inflammatory response, significant higher collagen deposition and angiogenesis compared with control wounds. The combined treatment PRGF+ASCs showed a significant faster cutaneous wound healing process.ConclusionsThe combined treatment PRGF+ASCs showed the best results, suggesting this is the best choice to enhance wound healing and improve aesthetic results in acute wounds.

Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study.

to study the efficacy and safety of the use of subconjunctival triamcinolone acetate alone or in combination with mitomycin C as a modulator of trabeculectomy healing in rabbits. we submitted thirty male, albino, New Zealand rabbits to bilateral trabeculectomy. We divided the animals into four experimental groups with 15 eyes per group: control, mitomycin C, triamcinolone acetate and triamcinolone acetate + mitomycin C. We performed aplanation tonometry and clinical analysis of the bleb through the Moorfields Graduation System in the postoperative period. For the evaluation of healing, we carried out the quantitative analysis of the inflammatory infiltrate (polymorphonuclear) through Hematoxylin & Eosin staining, and vascular proliferation, through immunohistochemistry. we observed a significant decrease in postoperative intraocular pressure in all groups compared with the preoperative pressure (p<0.001). However, there was no difference between groups (p=0.186). The triamcinolone + mitomycin C acetate group presented better indices as for the maximum bleb height and vascularization of the bleb central area (p=0.001); in addition, there was a lower inflammatory response (p=0.001) and lower vascular proliferation (p=0.001) in the intermediate phase of the study compared with the monotherapies. the combination of mitomycin C and triamcinolone acetate resulted in a synergistic action between these agents, with broader and more diffuse blebs, less inflammatory infiltrate and less vascular proliferation in the intermediate stages of follow-up in this animal model.

Evaluation of the Effect of Topical Hypericum perforatum Oil on Excisional Palatal Wound Healing in Rabbits

ABSTRACTAim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.

Electrical stimulation on open wound healing in Rabbits

Micro-amperage electrical stimulation (MES) on the healing process of skin wound in rabbits was studied. Twenty adult New Zealand white rabbits were randomly divided into four equal groups and a full thickness skin incision was made in each rabbit. This experimental group received an MES of 1000 μA (1mA) current intensity for 30 minutes twice a day. Swelling area of the wound of experimental groups were 11.1cd ± 0.2 mm, 10.8d ± 0.1 mm and 10.7cd ± 0.1mm at days 4, 7 and15, respectively. Elevation of sutured line (mm) of experimental groups was 2.4b ± 0.1, 2.1b ± 0.1, 2.2b ± 0.1 at days 4, 7 and 15, respectively. The average healing time was 30.4b, 28.4b and 26.4b in days 4, 7 and 15, respectively, significantly different from control groups. Number of fibroblasts and blood vessels were significantly higher in the experimental group than in control group. The result indicates that the application of MES significantly enhances the wound healing in rabbits.Bangl. vet. 2016. Vol. 33, No. 2, 51-61

Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model.

Antibiotic-loaded biomaterials (ALBs) have emerged as a potential useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

Comparative evaluation of bovine pericardial membrane and amniotic membrane in wounds skin healing in rabbits

The present study aimed to compare between the amniotic and pericardial membranes for the wound dressing models. Ten local breed rabbits have been used in the current study. They were divided into two main equal groups: Experiment (Amniotic and pericardial membranes) and control group. According to healing periods each group was subdivided into four subgroups (7, 14, 21 and 28) days post wounding. Specimens of amniotic membranes were collected from full term pregnant cows, and pericardium was obtained from abattoir immediately after slaughtering. The study was conducted on skin wound for experiment application site as full-thickness skin wounds (3×3 cm) were done on the dorsal thoracic sides. Histopathological evaluation of study depended on the degrees of inflammatory exudate, epithelialization, fibroplasia and type of leukocytes infiltration. Results revealed marked reduction of the inflammatory phase during all periods of post treatment with amniotic membrane, the degree of epithelization and fibroplasia in addition to angiogenesis were enhanced in amniotic and pericardial dressed wounds during period of 14 and 21 days. The study concluded that no significant differences are between the pericardial membrane and of amniotic membrane in wound healing of skin.

Topical Administration of Spironolactone-Loaded Nanomicelles Prevents Glucocorticoid-Induced Delayed Corneal Wound Healing in Rabbits.

The objective was to investigate whether mineralocorticoid receptor antagonism using a novel topical micellar formulation of spironolactone could prevent glucocorticoid-induced delayed corneal wound healing in New Zealand white rabbits. Spironolactone micelles (0.1%, w/v) with a mean number weighted diameter of 20 nm were prepared using a pegylated copolymer (mPEG-dihexPLA) and showed a preliminary stability of at least 12 months at 5 °C. Preclinical studies in New Zealand white rabbits demonstrated that the 0.1% spironolactone micellar formulation was well-tolerated since no reaction was observed in the cornea following multiple daily instillation over 5 days. As expected, the preclinical studies also confirmed that dexamethasone significantly delayed epithelial wound healing as compared to untreated control (percentage re-epithelialization after day 4: 84.6 ± 13.9% versus 99.5 ± 1.0% for the control, p < 0.05). However, the addition of the 0.1% spironolactone micellar formulation significantly improved the extent of re-epithelialization, countering the dexamethasone induced delayed wound healing with a percentage re-epithelialization that was statistically equivalent to the control (96.9 ± 7.3% versus 99.5 ± 1.0%, p > 0.05). The biodistribution study provided insight into the ocular metabolism of spironolactone and hence the relative contributions of the parent molecule and its two principal metabolites, 7α-thiomethylspironolactone and canrenone, to the observed pharmacological effects. Comparison of the efficacies of spironolactone and potassium canrenoate (a water-soluble precursor of canrenone) in overcoming the dexamethasone-induced delayed wound healing confirmed that the former had greater efficacy. The results pointed to the greater potency of 7α-thiomethylspironolactone over canrenone as a mineralocorticoid receptor antagonist, which explained its superior ability in countering the glucocorticoid-induced overactivation that was responsible for the delayed wound healing. In conclusion, the preliminary results supported the above-mentioned hypothesis suggesting that coadministration of mineralocorticoid receptor antagonists to patients under glucocorticoid therapy might prevent the deleterious effects of glucocorticoids on complex corneal wound healing processes.