1,720,983 research outputs found
Hyaluronic acid as an accessory scaffold and carrier for growth factors in bone healing
BACKGROUND: Cells, growth factors (GFs), and scaffold are three essential factors for tissue engineering. Our previous studies suggested that multiple applications of human amnion growth factors (AGF) into osseous defects could “mimic in-utero” growth. However, micro-gaps still exist between the scaffold and recipient tissue. We hypothesized that hyaluronic acid (HA) could act an accessory scaffold and gradually release active components of AGF and improve bone healing.
MATERIALS AND METHODS: Calvaria from 50 7–9-day old CD1 neonatal mice were harvested, and a 2 mm defect punch made in each one. A type I collagen membrane with AGF alone or with HA at different concentrations applied over the defect. The culture medium was changed every 2-3 days and collected for alkaline phosphatase (ALP) and protein analysis.
RESULTS: A single dose of AGF combined with 0.125% HA increased cellular infiltration into the defect area more than AGF with no HA or a lower concentration of HA (0.0625%). A single dose of AGF with HA can improve bone healing.
CONCLUSION: A single dose of AGF with HA as an extra scaffold and a carrier can achieve bone formation like multiple dosages of AGF and reduce the number of clinical applications needed
The role of ascorbic acid, osteoblast seeding, and insulin on bone formation in novel in-vivo bone model
OBJECTIVE: To determine the effects of vitamin C and insulin on osteoblasts harvested from neonatal mouse calvaria. To determine the effects of experimental media (vitamin C and insulin and a combination) on the ex-vivo live bone organ culture model and explore the capacity of addition of osteoblasts to allow for bone formation within a critical defect. To use the chick chorioallantoic membrane (CAM) model to explore bone formation within critical bone defect.
METHODS: Osteoblasts were harvested from neonatal mice were tested using four types of experimental media: control DMEM, media prepared with 150 μg/ml vitamin C, 10 nM media, or a combination of both vitamin C, insulin, and a combination of vitamin C and insulin media. Cell were cultured for 18 days at 37°C. Neutral red was done to identify cellular activity and silver nitrate to detect calcium deposits. Two types of scaffolds were inserted into the defect: collagen membrane scaffold and NuOss (xenograft) with collagen scaffold. After 30 days the samples were collected for histological analysis. Neonatal mouse calvaria were harvested and a 2mm critical defect made on each calvaria. Each calvaria received a scaffold of collagen or NuOss with or without osteoblasts with one of three experimental media within the CAM model. After 7 days, the amnion membrane of the egg was dropped and a window was made. The calvaria with the scaffold samples were placed on the amnion membrane. The eggs were incubated for 10 days then the experiment was terminated. Calvaria were collected and processed for histological evaluation.
RESULTS: Neutral red and silver nitrate of 2D in-vitro cells revealed calcium deposits in culture well using vitamin C media, cell cultured with insulin media showed calcium deposits and cell morphological change, and cell cultured with a combination of vitamin C and insulin media showed the most calcium deposits and morphological changed. Ex-Vivo samples with collagen scaffold had bone thickening but not enough nutrients for bone regeneration, despite the addition of cells. The collagen scaffold is a more suitable material than xenograft due to particle size. The CAM model showed new bone formation and new vessels were most abundant in areas closest to lining cells in collagen samples. Samples with additional osteoblasts added showed greater results. NuOss scaffold samples did not show the same bone formation or vessel growth.
CONCLUSIONS: The results indicate and confirm the basic principles of tissue engineering. In order to have bone regeneration more cells allow for better results. The quality of the scaffold is important and should have stability as well as enough space for cellular migration and recruitment for new blood vessel to support regeneration of bone to its original state
The role of the piezoelectric knife in accelerating bone healing
BACKGROUND: Piezoelectric surgery (PIEZO) uses ultrasonic vibration to cut hard tissue without damaging adjacent soft tissues. Our previous studies indicated that PIEZO enhanced bone turnover compared to a conventional rotary bur (BUR) in rat tibia wounds by inducing the regional acceleratory phenomenon (RAP). PIEZO induced osteocyte apoptosis without damaging blood vessels during Day 1, 3 and 7 of rat tibia healing. We hypothesized that PIEZO increased bone turnover by activation of osteocyte apoptosis with a controlled inflammatory response. This study evaluated early morphological changes in tibial defects caused by either PIEZO or BUR.
MATERIALS & METHODS: We created surgical defects in tibia by either PIEZO or BUR in 9–10-week-old Sprague-Dawley rat tibias (n=4). We evaluated tissue responses by using H&E, Masson’s Trichrome and TRAP stains on Day 1, 3 & 7 after surgery. The surgical defect beneath the soft tissue was located using Computed Tomography (CT).
RESULTS: On postoperative Day 1, there was no significant blood vessel change or cellular extravasation in the PIEZO group. In contrast the BUR group had extravasation of leukocytes and increased blood vessels' size. On Day3, there was no significant inflammation or morphological changes to blood vessels in the PIEZO group. Empty lacunae adjacent to the defect area suggested osteocyte apoptosis. In the BUR group, blood vessels returned to an average size and the leukocyte population was reduced and bone adjacent to the lesion was unaffected, and intact osteocytes were in the lacunae. On Day 7 there was increased in osteoclastic activity in Piezo compared the BUR group.
CONCLUSION: These results suggested that PIEZO induced osteocyte apoptosis, increased bone turnover with a controlled inflammatory response and protected the bone blood vessel network
Resolvin E1 as a growth factor in bone restoration
AIM & HYPOTHESIS: Resolvins, derived from omega-3 fatty acids, may actively resolve inflammation. Resolvin E1 (RvE1) binds to Chem-R23 as an endogenous anti-inflammatory and pro-resolving lipid mediator. We hypothesized that RvE1 may also activate osteoblasts to restore critical size bone defects in a calvarial model.
MATERIALS & METHODS: An in-vitro calvarial culture system was used to evaluate the stimulative effects of RvE1 compared to Amniotic Growth Factor (AGF) (a known stimulant in this system) on critical size defects under static conditions. Calvaria harvested from 10 mice and separated into 20 calvaria halves were cultured under conditions favoring bone formation. The test groups were defect only, defect plus a collagen membrane, defect plus a collagen membrane plus RvE1, and defect plus a collagen membrane plus AGF. The effect of RvE1 and AGF on healing of a critical size bone defect was assessed with both histological evaluation and alkaline phosphatase assays.
RESULTS: RvE1 binds in a receptor-ligand interaction with Chem-R23 in the periosteum to stimulate cellular proliferation and migration into a critical size bone defect of neonatal mouse calvaria.
CONCLUSION: These results suggest that RvE1 has a direct effect on osteoblast activity at and around the edge of a critical size 2 mm defect without an inflammatory reaction
Comparison of osseointegration in piezoimplants versus cylindrical implants
BACKGROUND: Dental implants have been successful for the restoration of edentulous areas, but current techniques are inadequate in areas lacking sufficient bone volume. Piezoelectric surgery has shown encouraging effects on both osseous healing. A new wedge-shaped titanium PiezoImplant requires piezoelectric osteotomy. This study compares PiezoImplants to conventional threaded cylindrical shaped implants by microcomputed tomography and histology to assess osseointegration, tissue response, and alveolar ridge changes.
METHODS: After 3 months post-extraction, 18 conventional cylindrical implants and 18 wedge-shaped PiezoImplants were placed using a split-mouth design in 3 adult mini pigs. The cylindrical implant sites were prepared for osteotomy with rotary instrumentation while the PiezoImplant sites were prepared with piezoelectric surgical inserts. One animal was sacrificed at 4, 8, and 12 weeks post operation. Quantitative µCT and histological analysis evaluated bone volume, osseointegration, and post-operative cellular events.
RESULTS: The results of a multivariable linear regression model demonstrated that the PiezoImplants, arch location, and time were significant factors on higher BV/TV percentage. Bone to implant contact (BIC) analysis by high resolution microscopy and histomorphometry indicated osseointegration though intimate contact between implants and adjacent alveolar bone in both groups. The tissue response displayed no evidence of abnormal healing and the PiezoImplant was classified as a non-irritant.
CONCLUSION: The combination of piezoelectric osteotomy and newly designed PiezoImplants had favorable effects on wound healing and osseointegration compared to conventional cylindrical implants. These novel wedge-shaped implants may be beneficial for narrow ridge spaces without additional ridge augmentation. Further research is needed to establish clinical validity
Study on porphyromonas gingivalis- and porphyromonas endodontalis- mediated signaling pathway
It is known that anaerobic microbes like Porphyromonas gingivalis (P. gingivalis) are involved in the progression and initiation of multiple forms of periodontal disease such as chronic periodontitis. However, in order to culture this gram-negative anaerobic microbes in the laboratory we need a long time (about 72 hours) with a complete absence of oxygen (≤0.001%) to reach optimal cell density. Therefore it is usually treated in an anaerobic chamber. Because this traditional method to culture P. gingivalis is costly and time consuming, we tried to elaborate in this study a new, rapid and less expensive method for culturing the anaerobes, such as P. gingivalis and P. endodontalis. With the use of a rotary shaker under anaerobic conditions, it would seal the bacterial growth media from oxygen exposure using a mineral oil overlay. Additional analysis by western blot helped us to study more about the cell’s biological functions. As a result, we found that the RAW264.7 cells treated by P. gingivalis or P. endodontalis showed three groups of kinase phosphorylation levels. As these kinases are key factors for the bacteria induced inflammation, we are interested to find how to reduce such bacteria (i.e. P. gingivalis and P. endodontalis) induced inflammation via regulation of these related kinase phosphorylation in future studies.
Based on our experiment, we believe that this method can be suitable for growing most species of anaerobic bacteria. Thus, we envision that this new method could be widely used in areas of both research and industry in the near future
A classification of maxillary premolar sockets in relation to the osseous housing for immediate implant placement
The aim of this study was to establish a classification system for use in immediate implant placement by examining fresh extraction sockets in maxillary premolars and evaluation of the varying morphologies using CBCT imaging. Selection criteria included dentulous patients ages 15-85 that had CBCT imaging taken for varying treatment. A total of 400 maxillary premolars were classified by their root morphology as Type I (two-rooted premolar with interradicular bone), II (fused roots with mesiodistal alveolar constriction) or III (single blunted root with no interradicular bone). The internal root angle was measured for all Type 1 maxillary first premolars (n=40), as well as the interradicular septal bone height. A Type 1 premolar socket is present in 32% of the sampled maxillary first and second premolars. Type 2 socket was present in 22% of premolars, and type 3 socket was present in 46% of premolars. The average internal angle formed between the long axis of the crown versus the long axis of the palatal root was 11.46 ± 4.35° (range 4° to 20.7°). The average interradicular septal bone height was of 6.9 ± 1.6 mm (range 3.28 to 9.61). Type I root form had the highest incidence at maxillary first premolars sites and has the most alveolar bone available, thus having a higher probability for primary stability. The type III root form is most common in the maxillary second premolar site and has the least amount of alveolar support for immediate implant placement. The angulation and alveolar bone support provided by the palatal root in Type I root form maxillary first premolar sites may provide stability for an immediate implant at an appropriate prosthetic position
Instigation in TNF alpha promoter activity in response to LPS
LPS-induced activation of transcription factors has been shown to be a key regulator of tumor necrosis factor-α (TNF-α) production. TNF-α synthesis may be attenuated in immune cells exposed to phosphodiesterase (PDE) inhibition after challenge with various pro-inflammatory stimulants. The signaling mechanisms affected by PDE inhibition that led to down-regulation of TNF-α production are not well characterized in inflammatory cells. Activation of certain transcription factors has been found to reduce TNF-α-induced inflammation by downregulating TNF-α promoter activity. The pathways by which these activated transcription factors downregulate TNF-α promoter activity are largely unknown. The overall aim of this study was to determine the biological function of these factors in LPS/TNF mediated signaling.
Aim 1: to clone mouse or human TNF-α promoter DNA.
Aim 2: analyze TNF-a promoter activit
Retrospective review of pre surgical variables associated with marginal bone loss measured at 2nd stage abutment surgery for endosseous dental implants
AIM: To measure marginal bone loss around endosseous dental implants at 2nd stage abutment surgery and retrospectively evaluate the association of pre-surgical variables with bone findings.
MATERIALS AND METHODS: Two implant systems were included in the study design. Straumann Bone Level Tapered SLActive and Nobel Biocare Replace Conical Connection. Implants were placed by the same resident from the Periodontics department. Clinical measurements of bone level were recorded at the time of placement and then again at 2nd stage surgery at four different points (mesial, lingual, buccal, distal).
RESULTS: Five implants were evaluated in the study. Bone loss averages ranged from 0-1.0mm. Nobel implants had an average loss of .75mm and Straumann implants had an average loss of .67mm.
CONCLUSION: Many variables contribute to marginal bone loss around endosseous dental implants at 2nd stage abutment surgery. The current research was designed to understand the relationship between these variables and early marginal bone loss. All implant samples included here were defined as control because of ≤1.0mm bone loss per IRB protocol
Impact of chronic inflammation induced by oral or gut bacteria on the integrity of blood-brain barrier and its relationship to Alzheimer’s disease
2025Alzheimer’s disease (AD) is the leading cause of dementia, affecting approximately one in nine Americans aged 65 and older. Chronic peripheral inflammatory conditions, such as periodontitis and gut dysbiosis, are increasingly recognized as potential contributors to AD pathogenesis. Porphyromonas gingivalis (P. gingivalis), a keystone periodontal pathogen, has been linked to neuroinflammation and cognitive decline, possibly via disruption of the blood-brain barrier (BBB). This study investigated the effects of chronic exposure to lipopolysaccharides (LPS) derived from oral (P. gingivalis) and gut (Escherichia coli) sources on BBB integrity and cognitive function.Male C57BL/6 mice (n=24) were treated with P.g-LPS, E. coli-LPS, or PBS via subcutaneous osmotic pumps over 28 days. Behavioral testing included the Morris Water Maze and Y-Maze Spontaneous Alternation Test. BBB integrity was assessed using Evans Blue dye extravasation, with immunohistochemistry and Western blotting performed to evaluate expression of tight junction proteins ZO-1 and occludin.
Mice exposed to LPS, particularly from P. gingivalis, demonstrated significant cognitive deficits without corresponding increases in BBB permeability. While Western blot analysis indicated a modest reduction in ZO-1 levels in the P.g-LPS group, this did not reach statistical significance.
These findings suggest that cognitive impairment can arise from chronic systemic inflammation even in the absence of gross BBB disruption. This study highlights peripheral inflammation as a potential early target for AD intervention
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