Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model.

OBJECTIVES: The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement. MATERIALS AND METHODS: Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers. RESULTS: Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant. CONCLUSION: The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.

Dental follicle stem cells in bone regeneration on titanium implants.

BACKGROUND: We aimed to demonstrate that DF stem cells from impacted molars and canines can be used to improve bone regeneration on titanium implants surfaces. This study highlights the presence of stem cells in DF, their potential to adhere and differentiate into osteoblasts on different types of titanium surfaces. RESULTS: Isolated cells from the harvested DF tissue from impacted canine/molars, expressed stem cells markers. Differentiation into bone cells was induced in presence or absence of BMP-2 and TGFß1. The presence of growth factors until 28 days in medium maintained the cells in an earlier stage of differentiation with a lower level of specific bone proteins and a higher expression of alkaline phosphatase (ALP). Influence of titanium implants with different bioactive coatings, hydroxyapatite (TiHA) and with silicatitanate (TiSiO2), and porous Ti6Al7Nb implants as control (TiCtrl), was studied in terms of cell adhesion and viability. Ti HA implants proved to be more favorable for adhesion and proliferation of DF stem cells in first days of cultivation. The influence of titanium coatings and osteogenic differentiation mediums with or without growth factors were evaluated. Additional BMP-2 in the medium did not allow DF stem cells to develop a more mature phenotype, leaving them in a pre-osteogenic stage. The best sustained mineralization process evaluated by immuno-cytochemical staining, scanning electron microscopy and Ca(2+) quantification was observed for TiHA implants with a higher expression of ALP, collagen and Ca(2+) deposition. Long term culturing (70 days) on titanium surfaces of DF stem cells in standard medium without soluble osteogenic inducers, indicated that HA coating is more favorable, with the acquisition of a more mature osteoblastic phenotype as shown by immunocytochemical staining. These findings demonstrated that even in absence of exogenous osteogenic factors, TiHA implants and in a lesser extent TiCtrl and TiSiO2 implants can induce and sustain osteogenic differentiation of DF stem cells, by their chemical and topographical properties. CONCLUSIONS: Our research demonstrated that DF stem cells have a spontaneous tendency for osteogenic differentiation and can be used for improving bone regeneration on titanium implants surfaces.

Engaging a polylactide copolymer in oral tissue regeneration: first validation of Suprathel® for guided epithelial and osseous healing.

The present study investigated the capacity of Suprathel® (a copolymer membrane, so far validated for skin regeneration) to also regenerate oral tissue - mucosa and bone, by comparing this biomaterial, in a split-mouth rabbit model, to Mucoderm®, a xenogeneic collagen matrix certified for keratinized oral mucosa healing. The clinical reason behind this experimental animal model was to determine whether the benefits of this advanced skin regeneration product (Suprathel®) could be conveyed for future evaluation in clinical trials of oral tissue regeneration in humans. The outcomes of this study validated the use of Suprathel®, a terpolymer of polylactide with trimethylene carbonate and ε-caprolactone, for stimulation of oral epithelium and alveolar bone regeneration in rabbits. Both Suprathel® and Mucoderm® exhibited comparable results and the null hypothesis stating a comparable regenerating effect of these two materials could not be rejected.

Effect of Liposomal Curcumin on Acetaminophen Hepatotoxicity by Down-regulation of Oxidative Stress and Matrix Metalloproteinases.

BACKGROUND/AIM: The hepatoprotective role of various molecules in drug-induced hepatotoxicity arouses great interest. We investigated the effect of liposomal curcumin (LCC) on experimental acetaminophen (APAP)-induced hepatotoxicity. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups, and the effect of two LCC concentrations was studied: group 1 - 1 ml intraperitoneal (i.p.) saline, group 2 - APAP pretreatment, group 3 - APAP+silymarin (extract of the silybum marianum with anti-inflammatory, anti-oxidant, and anti-fibrotic properties), group 4 - APAP+LCC1, group 5 - APAP+LCC2. The biomarkers of oxidative stress (nitric oxide and malondialdehyde) and antioxidant status of plasma (thiols and catalase), TNF-α, MMP-2 and MMP-9 serum levels were evaluated. RESULTS: An improvement in oxidative stress, antioxidant status, and TNF-α, MMP-2 and MMP-9 levels was obtained in groups pretreated with LCC compared to silymarin treatment, in a dose-dependent manner. Histopathological examination reinforced the results. CONCLUSION: Liposomal curcumin improves the oxidative stress/antioxidant balance and alleviates inflammation in experimental APAP-induced hepatotoxicity.

Atelo-collagen type I bovine bone substitute and membrane in guided bone regeneration: a series of clinical cases and histopathological assessments.

Absorbable atelo-collagen type 1 represents a new approach for guided bone regeneration with several reported advantages such as: osteoblast attachment, proliferation, mineralization potential, absorption of growth factors and inhibition of bacterial pathogen colonization. The aim of this study was to assess the clinical, radiological (preoperative width, re-entry width, gain), Periotest measurements and histologic benefits of atelo-collagen-derived bovine bone grafts (ImploBone) in combination with an atelo-collagen type I barrier membrane (ImploSorb) for guided bone regeneration (GBR) of atrophic alveolar crest in thirteen patients. Eleven patients underwent simultaneous GBR with implant insertion, two had initial GBR procedure followed by implant placement after 6 months of healing. Ridge augmentation was performed using an atelo-collagen membrane (ImploSorb, Bioimplon, Germany) and a combination of 50% ABBM (ImploBone, granule size 0.5-1mm, BioImplon Germany) mixed with 50% autologous bone. It was found that simultaneous GBR with implant placement resulted in a 35% gain at bone defect level (preoperative width 5.03±1.25 mm, re-entry width 6.81±0.98 mm, gain 1.78±1.71 mm). Implant placement performed in a 2 stage surgery 6 months following GBR was linked with a 63,9% gain at bone defect level (preoperative width 3.79±1.10 mm, re-entry width 6.22±1.41 mm, gain 2.43±1.43 mm). The total gain in both groups was 41,9% utilizing these novel biomaterials (preoperative width 4.68±1.32 mm, re-entry width 6.65±1.12 mm, gain 1.96±1.64 mm). This case series study presents a protocol where GBR can be performed either simultaneously to implant placement or delayed with this innovative biomaterial to favor bone regrowth. Future randomized controlled clinical trials are needed to further validate the bone-promoting potential of atelo-collagen-based biomaterials for bone regeneration.

Histological Change in Soft Tissue Surrounding Titanium Plates after Jaw Surgery.

The aim of this study was to evaluate the microscopic structure of soft tissue covering titanium plates and screws used in jaw surgery (mandible fracture and orthognathic surgery), after a minimum period of 12 months from insertion, and to quantify the presence of any metallic particles. Periosteum covering the osteosynthesis plates was removed from 20 patients and examined by light microscopy in order to assess the cell morphological changes and the possibility of metal particles presence in the soft tissue. Local signs of tissue toxicity or inflammation were taken into consideration when evaluating the routine removal of titanium maxillofacial miniplates. No signs of screw loosening or acute inflammation were detected on the osteosynthesis site, but de-coloration of the periosteum was seen, and metallic particles were observed to have migrated into the soft tissues. Even if the titanium is well-tolerated by the human body in time, without severe local or general complications, our findings suggest that plate removal should be considered after bone healing has occurred.