Evaluation of the osteoconductive properties of scaffold containing platete-enriched-fibrin (PRF) with three calcium phosphate (TCP) in the alveolar socket repair after tooth extraction: An animal study.

Bone regeneration can be accomplished through osteogenesis, osteoinduction, and osteoconduction mechanisms. This study aimed to investigate the properties of the PRF scaffold with tricalcium phosphate nanoparticles in socket preservation in an animal model. Fabrication of PRF performed. In this experimental study, 18 rats were divided into three negative control, PRF, and PRF/TCP groups. The mechanical and chemical tests including swelling rate, degradation time, and MTT tests were applied to the scaffolds. In each animal, the first maxillary right molar was extracted, and extraction sites of test groups were filled with a resorbable biocompatible biomaterial in situ hardening bone substitute. After 2 and 4 weeks all animals were sacrificed and examined histopathologically and with qRT-PCR. Histological results showed TCP in combination with PRF accelerates bone regeneration with the highest amount of lamellar bone and collagen formation compared to the control and PRF alone. Mechanical and chemical tests on the scaffolds showed the addition of TCP to the PRF scaffold decreases the swelling rate and increases the degradation time. qRT-PCR showed expression of osteogenic genes increased significantly (p < 0.05) in PRF/TCP and PRF, respectively. In conclusion, the gelatin hydrogel containing PRF/TCP scaffold led to more bone formation after tooth extraction. Therefore, the injectable PRF\TCP hydrogel is a promising candidate for bone repair and regeneration.

Effects of FTY720 on Neural Cell Behavior in Two and Three-Dimensional Culture and in Compression Spinal Cord Injury.

Introduction: The present study aimed to evaluate the effects of FTY720 as a neuromodulatory drug on the behaviors of neural stem/progenitor cells (NS/PCs) in two-dimensional (2-D) and three-dimensional (3-D) cultures and in spinal cord injury (SCI). Methods: The NS/PCs isolated from the ganglionic eminence of the 13.5-day old embryos were cultured as free-floating spheres. The single cells obtained from the second passage were cultured in 96-well plates without any scaffold (2-D) or containing PuraMatrix (PM, 3-D) or were used for transplantation in a mouse model of compression SCI. After exposure to 0, 10, 50, and 100 nanomolar of FTY720, the survival, proliferation, and migration of the NS/PCs were evaluated in vitro using MTT assay, neurosphere assay, and migration assay, respectively. Moreover, the functional recovery, survival and migration capacity of transplanted cells exposure to 100 nanomolar FTY720 were investigated in SCI. Results: Cell survival and migration capacity increased after exposure to 50 and 100 nanomolar FTY720. In addition, higher doses of FTY720 led to the formation of more extensive and more neurospheres. Although this phenomenon was similar in both 2-D and 3-D cultures, PM induced better distribution of the cells in a 3-D environment. Furthermore, co-administration of FTY720 and NS/PCs 7 days after SCI enhanced functional recovery and both survival and migration of transplanted cells in the lesion site. Conclusions: Due to the positive effects of FTY720 on the behavior of NS/PCs, using them in combination therapies can be an appealing approach for stem cell therapy in CNS injury.

A New and Simple Method for Spinal Cord Injury Induction in Mice.

Introduction: Spinal Cord Injury (SCI) is a devastating disease with poor clinical outcomes. Animal models provide great opportunities to expand our horizons in identifying SCI pathophysiological mechanisms and introducing effective treatment strategies. The present study introduces a new murine contusion model. Methods: A simple, cheap, and reproducible novel instrument was designed, which consisted of a body part, an immobilization piece, and a bar-shaped weight. The injury was inflicted to the spinal cord using an 8-g weight for 5, 10, or 15 minutes after laminectomy at the T9 level in male C57BL/6 mice. Motor function, cavity formation, cell injury, and macrophage infiltration were evaluated 28 days after injury. Results: The newly designed instrument minimized adverse spinal movement during injury induction. Moreover, no additional devices, such as a stereotaxic apparatus, were required to stabilize the animals during the surgical procedure. Locomotor activity was deteriorated after injury. Furthermore, tissue damage and cell injury were exacerbated by increasing the duration of weight exertion. In addition, macrophage infiltration around the injured tissue was observed 28 days after injury. Conclusion: This novel apparatus could induce a controllable SCI with a clear cavity formation in mice. No accessory elements are needed, which can be used in future SCI studies. Highlights: A simple and precise method has been introduced for creating Spinal Cord Injury (SCI) in mice by a novel device.The device consists of a body part, an immobilization piece, and a bar-shaped weight.Assessment of locomotor activity, tissue damage, and macrophage infiltration confirmed the capability of the new SCI method.Reduction of adverse spinal movements and working without any accessory elements are the key points of this new animal model of SCI. Plain Language Summary: Spinal Cord Injury (SCI) is a medical problem that can cause the permanent motor and sensory dysfunction. Traffic accidents, falls, and violence are the most frequent causes of SCI, often affecting young people. Patients and even their families may encounter other problems, including reducing life quality, psychological burden, and enormous medical costs. Despite scientific and technological advances, no effective treatment has been found for SCI. Therefore, animal models help study damage mechanisms and evaluate novel treatment strategies. All SCI research centers require an economical and reproducible device without using complex surgical procedures by experienced surgeons to minimize variations in damage to the spinal cord. In this study, a simple, cheap, and reproducible novel instrument for SCI induction is introduced. The instrument consists of various parts, including a body part, an immobilization piece, and a bar-shaped weight. An 8-g weight was used for 5, 10, or 15 minutes to inflict injury to the spinal cord. Behavioral and tissue studies indicated that SCI could be induced in rodents in different severity without other elements. This instrument can be used in future investigations for SCI studies, including tissue engineering, stem cell therapy, and drugs delivery to access effective treatment.

Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix-embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury.

Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod-incorporated poly lactic-co-glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion-evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix-encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV-visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co-administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three-dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.

The effects of minocycline on proliferation, differentiation and migration of neural stem/progenitor cells.

Purpose: There are several attempts to enhance the capacities of neural stem/progenitor cells (NS/PCs) as a probable source of stem cell therapy for neurodegerative diseases. The evidence shows that minocycline has several non-antibacterial effects in neurodegenerative diseases. We aimed to investigate the effect of minocycline on proliferation, differentiation and migration of embryonic NS/PCs.Materials and methods: NS/PCs extracted from ganglionic eminence of 13.5-day embryonic mice were cultured according to neurosphere protocol. After second passage they were exposed to different doses of minocycline for 7 days. The number and diameter of neurospheres were assessed to evaluate their proliferation. Migration was estimated based on the distances traveled by the cells. Because of the importance of NS/PCs behaviors in 3-dimentional environment, all assessments were done in 3-dimentional and 2-dimentional cultures. Moreover, the fate of NS/PCs to neuron or glial cells was studied.Results: NS/PCs exposed to 1 µg/ml and 10 µg/ml of minocycline and those in untreated group traveled significantly longer distances compared to those treated with 50 µg/ml and 100 µg/ml of minocycline. In addition, higher doses of minocycline reduced the NS/PCs proliferation remarkably compared to control condition just in 2-D culture. However, the differentiation capacity of cells was not significantly affected by 1 and 10 µg/ml of minocycline.Conclusion: The behavior of NS/PCs depends on minocycline dose as well as the characteristics of environment.

Tooth color alteration after debonding in orthodontic patients with adhesive removal using composite bur or tungsten carbide bur: a single center, randomized controlled clinical trial / Alteração da cor do dente após descolagem de braquetes em pacientes ortodônticos pela remoção de adesivo usando broca de compósito ou broca carbide de tungstênio: ensaio clínico unicêntrico randomizado e controlado

Objective: The objective of this study was to determine whether recently developed fiber reinforced composite burs provided better results by comparing tooth discoloration after debonding of orthodontic brackets. Material and Methods: A split-mouth, randomized controlled trial was carried out in one orthodontic office; including 23 patients with intact, vital and caries-free four upper incisors aged 12 to 30 years who completed their fixed orthodontic treatment. For each patient, upper central and lateral incisors on each side of the mouth were randomly selected to remove the adhesive with either a tungsten carbide bur (TC) (n = 46) or a fiber-reinforced composite bur (FC) (n=46). Color evaluation of each tooth was conducted at two time points: immediately after finishing and polishing procedure and two months afterwards. The primary outcome would be the amount of color change in each group during the post treatment phase. The participants, the person assessing the color change and the statistician were blinded to TC group assignment. Color changes in each group were analyzed with the Paired T-test. The color change corresponding to the resin removal method was also statistically analyzed with the Independent T-test at α=0.05 as the level of significance. Results: 86 teeth, 43 in each group, were analyzed. The ΔE value was 3.713±1.161, for teeth finished TC and 2.114±0.514 for teeth finished with FC (p<0.01). Conclusion: Adhesive removal with FC bur results in a more color-resistant tooth surface in comparison with tungsten carbide bur. (AU)

Objetivo: O objetivo deste estudo foi determinar se as brocas de material compósito reforçadas com fibras, recentemente desenvolvidas, proporcionam melhores resultados, pela comparação da descoloração dentária após a remoção de braquetes ortodônticos. Material e Métodos: Um ensaio clínico controlado randomizado com boca dividida foi realizado em um consultório ortodôntico, incluindo 23 pacientes, com idade entre 12 e 30 anos, com incisivos superiores intactos, vitais e livres de cárie, que completaram o tratamento ortodôntico com aparelho fixo. Para cada paciente, incisivos centrais e laterais superiores de cada lado da boca foram selecionados aleatoriamente para remover o adesivo ortodôntico com uma broca carbide de tungstênio (TC) (n = 46) ou uma broca de compósito reforçada com fibra (FC) (n = 46). A avaliação da cor de cada dente foi realizada em dois momentos: imediatamente após o acabamento e polimento e dois meses após. O resultado primário foi a quantidade de mudança de cor em cada grupo durante a fase pós-tratamento. Os participantes, a pessoa que avaliou a mudança de cor e o estatístico não tinham conhecimento da atribuição ao grupo TC. As mudanças de cor em cada grupo foram analisadas com o teste-t pareado. A mudança de cor correspondente ao método de remoção da resina também foi analisada estatisticamente com o teste-t independente considerando um nível de significância α = 0,05. Resultados: foram analisados 86 dentes, 43 em cada grupo. O valor de ΔE foi 3,713 ± 1,161, para dentes finalizados com broca TC e 2,114 ± 0,514 para dentes finalizados com broca FC (p <0,01). Conclusão: A remoção do adesivo com broca FC resulta em uma superfície de dente mais resistente à cor em comparação com a broca carbide de tungstênio (AU)