Healing of induced tongue defects using erythropoietin hydrogel (an experimental study on rats).

BACKGROUND: Tongue is complex muscular organ that may be affected by recurrent or chronic ulcerations and malignances that require effective treatment to enhance healing and tissue regeneration. So, this study aimed to evaluate the efficiency of erythropoietin (EPO) hydrogel as an anti-inflammatory and an inducer of neovascularization during healing of induced rats' tongue defects. METHODS: Thirty six rats were divided into three groups; Group I (negative control): tongues were left without ulceration and received no treatment, Group II (positive control): tongue defects were prepared on the tongues' dorsal surfaces, measuring (5 mm × 2 mm) using a tissue punch rotary drill for standardization, and left untreated, Group III (EPO group): tongue defects were prepared as in group II, then injected circumferentially around wound margins with a single high dose of EPO hydrogel of 5000 U/kg on the day of defect preparation. Animals were euthanized on seventh and fourteenth days after treatment, tongue specimens were collected, and paraffin blocks were prepared and processed for histological assessment by hematoxylin and eosin stain and immunohistochemical evaluation of anti-iNOS and anti-VEGF followed by histomorphometrical analysis and the relevant statistical tests. RESULTS: At both time points, the EPO treated group showed significantly enhanced tissue regeneration marked by the histologically better regenerated tissue with well developed, thick walled and well-organized blood vessels and significant reduction in defect depth compared to positive control group. EPO group also showed significant decrease in iNOS and significant increase in VEGF antibodies indicating its anti-inflammatory and neovascularization effects respectively. CONCLUSION: EPO treatment can significantly accelerate regeneration and filling of tongue defects by reducing tissue inflammation and enhancing neovascularization. Therefore, EPO could be a potential therapeutic strategy for accelerating healing of tongue ulcers. However, further investigations are required to optimize the dose and unravel any potential side effects before its clinical application.

Photobiostimulation conjugated with stem cells or their secretome for temporomandibular joint arthritis in a rat model.

BACKGROUND: Temporomandibular joint (TMJ) arthritis is a debilitating, challenging condition and different methods have been implicated for its treatment. This study aimed to test the therapeutic potentials of low-level laser therapy (LLLT) associated with adipose derived stem cells (ADSC) or their derived secretome on a murine model induced arthritis. METHODS: Forty eight rats were divided into four groups where group I was the sham control, the rest of animals were subjected to arthritis induction using complete Freund's adjuvant, then divided as follows: group II received phosphate buffered saline (PBS) intraarticular injection and irradiation of 0 j/cm2, group III received ADSCs derived secretome and irradiation of 38 j/cm2, and group IV received ADSCs and irradiation of 38 j/cm2 as well. One and three weeks after treatment, animals were euthanized, and paraffin blocks were processed for histological assessment by hematoxylin and eosin stain with histomorphometrical analysis. Histochemical evaluation of joint proteoglycan content was performed through toluidine blue stain, and immunohistochemical staining by the proinflammatory marker tumor necrosis factor-α (TNF-α) was performed followed by the relevant statistical tests. RESULTS: The arthritis group showed histological signs of joint injury including cartilage atrophy, articular disc fibrosis, irregular osteochondral interface, and condylar bone resorption together with high inflammatory reaction and defective proteoglycan content. In contrast, the treated groups III and IV showed much restoration of the joint structure with normal cartilage and disc thickness. The inflammation process was significantly suppressed especially after three weeks as confirmed by the significant reduction in TNF-α positive immunostaining compared to the arthritic group, and the cartilage proteoglycan content also showed significant increase relative to the arthritic group. However, no significant difference between the results of the two treated groups was detected. CONCLUSION: LLLT conjugated with ADSCs or ADSCs derived secretome can efficiently enhance the healing of arthritic TMJs. Stem cell secretome can be applied as a safe, potent therapy. However, further investigations are required to unravel its mechanism of action and pave its way as a safe, novel, cell free therapy.

Comparison between Effect of Bisphosphonates, Concentrated Growth Factors or Combination on Rabbits' Tibial Bone Defects Healing: An Experimental Study.

AIM: This study was designed to evaluate the effect of bisphosphonates (BIS) or concentrated growth factors (CGF) or a combination of them on bone defect healing. MATERIALS AND METHODS: Bone defects of 3-mm width and 6-mm depth were prepared in 24 rabbit tibias unilaterally, then randomly divided into the following four equal groups: 1. Group I: No treatment 2. Group II: Treated by BIS 3. Group III: Treated by CGF 4. Group IV: Treated by BIS + CGF Animals were equally sacrificed at 4 weeks, and at 6 weeks then tibias were processed for hematoxylin and eosin (H&E) and Masson's trichrome (MTC) staining. The data were subjected to one-way analysis of variance (ANOVA) followed by post hoc Tukey test and unpaired Student's t-test. RESULTS: In group IV, the quality of newly formed bone was better than any other group with increased mineralization and decreased collagen, followed by group III, then group I, while group II showed the least favorable results. The statistical analysis showed a significant difference between groups. CONCLUSION: Mixing BIS with CGF showed the best healing, and bone quality results, followed by CGF-treated group, then control, and finally, BIS-treated group. CLINICAL SIGNIFICANCE: Using CGF as a scaffold and mixing it with BIS could help accelerate the healing of bone defects, reduce healing time, and minimize the risk of infection.

Effect of bone marrow mesenchymal stem cells on healing of temporomandibular joints in rats with induced rheumatoid arthritis.

The healing capacity of bone marrow mesenchymal stem cells (BMMSCs) has been evaluated in various studies. This study aimed to evaluate the effect of BMMSCs on the healing of temporomandibular joints (TMJs) with induced rheumatoid arthritis. Fifty healthy male Sprague Dawley rats were divided into three groups: group I (n = 10), negative control; group II (n = 20), positive control (induction of arthritis by adjuvant followed by intravenous injection of 0.1 ml of PBS); and group III (n = 20), intervention (as for group II but injected intravenously with 1 × 106  cells ml-1 of BMMSCs suspended in PBS). Half of the rats in each group were euthanized 3 wk after the start of the experiment and the other half was euthanized after 5 wk. Group I revealed normal TMJ features. Group II showed thickening of disc, thinning of cartilage, disordered bone trabeculae, and decreased in mean % area staining positive of collagen fibers at 3 wk, while at 5 wk these effects were more aggravated. Group III showed nearly normal thickness of disc and condylar cartilage, nearly normal arrangement of bone trabeculae and regenerated collagen fibers at 3 wk, while after 5 wk the TMJ features were almost normal. Two-way anova revealed statistically significant differences between groups. Thus, treatment of induced rheumatoid arthritis with BMMSCs shows promising results that need to be further investigated in humans.