Bone Tissue Healing Research Articles

Alternating electrical fields to stimulate osteogenic cells and biomimetic calcium phosphate-coated titanium substrates-A combinatorial approach to bone regeneration.

Biophysical stimuli such as alternating electrical fields can mimic endogenous electrical potentials and currents in natural bone. This can help to improve the healing and reconstruction of bone tissue. However, little is known about the combined influence of biomaterials and alternating electric fields on bone cells. Therefore, this study aimed to investigate the impact of both, biomaterials and alternating electric fields, on osteoblast as well as osteoclast differentiation. Initially, either RAW 264.7 or MC3T3-E1 cells were seeded on Ti6Al4V substrates as a load-bearing implant material, modified with biomimetic calcium phosphate (BCP), or uncoated as a reference. The cells were stimulated towards osteoclastic and osteoblastic differentiation via respective growth factors. The effects of BCP substrate modification on cell differentiation were examined after 7days for RAW 264.7 and after 14days for MC3T3-E1 cells. In a further series of tests, either RAW 264.7 or MC3T3-E1 cells were seeded on BCP-modified Ti6Al4V substrates, stimulated towards differentiation using growth factors, and further electrically stimulated via alternating electric fields of different voltages and frequencies. In parallel to the first test series RAW 264.7 and MC3T3-E1 cells were stimulated for 7 and 14days, respectively. Cell morphology was examined via scanning electron microscopy. Cell viabilities were assessed via WST-8 assay. Electrically stimulated MC3T3-E1 cell orientation was evaluated based on fluorescence microscopy images. Marker genes were examined via qPCR. While BCP increased osteoclast-specific gene expression, it had the opposite effect on osteoblast-related genes compared to respective cells seeded on uncoated Ti6Al4V substrates. ES with different parameters showed a broad cellular response due to electrocoupling. While cell viability assessments and gene expression analyses showed clear differences between ES samples and unstimulated controls, only minor cell morphology and orientation differences were observed. Furthermore, there was no clear trend towards a dominant influence of either voltage or frequency as control parameters. Further studies were initiated to investigate the underlying intracellular mechanisms targeted by ES. This work provides an introduction to the targeted control of cellular processes using defined electric fields. The optimization of voltage and frequency could provide therapeutic windows to control specific cellular functions and potentially improve bone regeneration and remodeling processes.

Use of Concentrated Growth Factor (CGF) in Reconstruction on Two Wall Bone Defect After Cystectomy: An Alternative to Traditional Regeneration - Case Report

Aim: The purpose of this clinical case report was to describe an alternative technique performed to ensure bone regeneration after removing a cystic lesion in the upper jaw. Bone defect after cystectomy was filled with autologous fibrin rich clots containing CGF.Materials and methods: A 45 years old female patient was suspected to have a cystic lesion with massive bone destruction on the vestibular and palatal walls between teeth 2.2 and 2.3. Concentrated growth factor (CGF) was used to cover the defect in order to favourite the bone grow. Results: After 12 months, the clinical and radiological follow-up examination showed that the tooth was asymptomatic and that the healing was in progress. Conclusions: this article describes a different way to treat a two-wall defect involving both the palatal and buccal bone, after removing a cystic lesion, with the use of CGF as an alternative to traditional use of autologous or heterologous bone. CGF fibrin could promote new bone formation in jaw defects, with benefit to the healing of bone tissue and, thus, is a promising bone repair material.

SURGICAL MANAGEMENT OF A LARGE MANDIBULAR CYST: A CASE REPORT

Large mandibular cysts have a series of complications including significant anatomical lesions such as bone destruction or maxillofacial deformity. Therefore, the effectiveness of simple conventional curettage of the cyst is not satisfactory. The aim of this study was to investigate several factors that can lead to a successful treatment planning such as an accurate 3D radiological evaluation by using CBCT, the importance of a correct microscopical root canal treatment and filling and the importance of using the A-PRF membrane after the primary enucleation of cysts and the filling of bone defect. Case report A 38-year-old patient presents with pain during mastication and swelling in the anterior mandibula. OPC and CT examination revealed a cystic lesion extending from the mesial of 3.4 to the mesial of 4.3. The endodontic retreatment of the four incisions and lower left canine was performed preoperatory, followed by piezo surgical complete cystic membrane enucleation under local anesthesia and intra-venous sedation. After the endodontic retreatment of 3.2, 3.1, 4.1 and 4.2 due to the large size of the bone defect, A-PRF membrane was used to improve healing of bonny defect. In this case it was used the Duoquattro* centrifuge. The patient was recalled every 1, 3, 6 months for routine intraoral examination. One year later, the CT evaluation revealed bone regeneration. Conclusions The treatment choice for a large mandibular cyst was represented by entirely enucleation of the cyst with intraoral approach using piezo surgical technology. The use of A-PRF membrane is an efficient adjuvant to surgical procedure witch improved bone remodeling and tissue healing, with no post-operative complications. One year later, the CT evaluation revealed bone regeneration.

Effect of low level laser therapy and bioactive glass in the treatment of periodontal infrabony defects: A randomized controlled clinical trial

Background: Several guided bone regeneration techniques have been used in the past aiming to treat infrabony defects with promising outcome. Recently, low level laser therapy (LLLT) has been introduced as an adjunctive tool with better bone and soft tissue healing due to its biostimulation and biomodulation properties. The aim of the present study is to evaluate the adjunctive effect of Gallium – Aluminium – Arsenide (GaAlAs) laser in the management of periodontal infrabony defects. Materials and method: This was a randomised controlled, double blinded, split mouth clinical study carried out on subjects with bilateral infrabony defects. Clinical parameters of plaque index (PI), gingival index (GI), probing pocket depth (PD) and clinical attachment level (CAL) were recorded as well as infrabony defect depth using radiovisiograph at baseline, 3 months and 6 months intervals. The test group was treated with bioactive glass and GaAlAs laser on the 1st, 3rd, 5th and 7th day following periodontal open flap surgery and the control group received bioactive glass only. All data were collected and analyzed using Wilcoxon signed rank test and paired t test. Results: A total of 15 subjects were enrolled in this study. There was a significant reduction in the PD (p=0.05), CAL (p=0.01) and in defect depth observed at 6 months interval in the test group compared to control group. Conclusion: Based on the current data, the application of LLLT as an adjunctive tool with bioactive glass may have a superior outcome in treating infrabony defects compared to bioactive glass alone.

EL HÁBITO DE FUMAR Y SU INFLUENCIA EN LA CONSOLIDACIÓN ÓSEA: UNA REVISIÓN INTEGRADORA

Smoking is considered one of the risk factors for various diseases, not only related to the respiratory system but also influencing the physiological processes of various organs and body systems. This article aims to deepen the understanding of the effects of smoking on bone healing by analyzing its molecular, cellular, and clinical bases. This process is subject to possible direct or indirect interferences from chemical substances such as nicotine. It is important to note that, besides conventional cigarettes, there is also indiscriminate use of electronic cigarettes, which, according to an analysis conducted by Pérez and Duarte (2022), have considerably higher nicotine levels than traditional cigarettes. Another study conducted by González et al. (2021) highlights the increasing popularity of these devices among young people, underscoring the importance of preventive measures. According to the National Institute of Traumatology and Orthopedics (INTO), inhaling tobacco smoke increases bone tissue healing time by 60%, thus delaying the body's ability to heal injuries and compromising bone absorption. The clinical repercussions of smoking on the quality and speed of bone recovery after fractures and orthopedic procedures are identified to improve understanding and develop specific clinical strategies and interventions for smoking patients. The specific objectives of this research were to: investigate the molecular and cellular mechanisms of the bone healing process, analyze the effects of smoking on the quality of the formed tissue, evaluate the influence of smoking on the bone healing time in patients after fracture or orthopedic surgery, and finally propose therapeutic strategies and preventive measures to improve bone healing. To this end, a bibliographic search was conducted on articles relevant to the topic using various means. The selection of articles was based on three stages, choosing those that met the inclusion criteria. During the development of this article, it is observed that smoking is an extended and ancestral practice, being a constant and emerging health problem. Additionally, it is considered a modifiable risk factor for decreasing bone density. In conclusion, the need for specific strategies to address complications in bone healing in smoking patients is highlighted.

Chitosan as a Templating Agent of Calcium Phosphate Crystalline Phases in Biomimetic Mineralization: Theoretical and Experimental Studies.

Highlighting the essential role of chitosan (CS), known for its biocompatibility, biodegradability, and ability to promote cell adhesion and proliferation, this study explores its utility in modulating the biomimetic mineralization of calcium phosphate (CaP). This approach holds promise for developing biomaterials suitable for bone regeneration. However, the interactions between the CS surface and in situ precipitated CaP still require further exploration. In the theoretical section, molecular dynamics (MD) simulations demonstrate that, at an appropriate pH level during the prenucleation stage, calcium ions (Ca2+) and hydrogen phosphate ions (HPO42-) form Posner-like clusters. Additionally, the interaction between these clusters and the CS molecule enhances system stability. Together, these phenomena facilitate the transition to subsequent heterogeneous nucleation on the surface of the organic matrix, which is a more controlled process than homogeneous nucleation in solution. Dynamic simulation results suggest that CS acts as a stabilizing matrix at pH 8.0 during biomimetic mineralization. In the experimental section, the effects of pH and the molecular weight of CS were investigated, with a focus on their impact on the crystal structure of the resulting material. X-ray diffraction and scanning electron microscopy analyses reveal that, under conditions of approximately pH 8.0 and a CS molecular weight of 20 000 g/mol, and controlled ion concentration, ultrasound radiation, and temperature, the dominant CaP phases in the material are carbonate-doped hydroxyapatite (CHA) and octacalcium phosphate (OCP). These findings suggest that CS, when adjusted for molecular weight and pH, facilitates the formation of CaP crystal phases that closely resemble the natural inorganic composition of bone, highlighting its protective and regulatory roles in the growth and maturation of crystals during mineralization. The theoretical predictions and experimental outcomes confirm the crucial role of CS as a templating agent, enabling the development of a biomimetic mineralization pathway. CS's ability to guide this process may prove valuable in the design of materials for bone tissue engineering, particularly in developing effective materials for bone tissue healing and regeneration.

Influence of Detonation Spraying Parameters on the Microstructure and Mechanical Properties of Hydroxyapatite Coatings.

The process of osteointegration depends significantly on the surface roughness, structure, chemical composition, and mechanical characteristics of the coating. In this regard, an important direction in the development of medical materials is the development of new techniques of surface modification and the creation of bioactive ceramic coatings. Calcium-phosphate materials based on hydroxyapatite have been proposed as bioactive ceramic coatings on titanium implants for the effective acceleration of bone tissue healing. To obtain bioactive ceramic coatings, pulse power sources are best suited, namely detonation spraying, in which the energy of the explosion of gas mixtures is used as a source of pulse action. The pulse mode of operation in the detonation spraying method is preferable for the formation of bioactive ceramic coatings. It provides a high velocity of hydroxyapatite particles, which promotes their effective fixation on the titanium substrate, while minimizing the heating of the material. This approach preserves the substrate structure and improves the coating adhesion. Four different types of coatings with varying O2/C2H2 molar ratios, ranging from 2.6 to 3.7, were obtained using detonation spraying. Powders and obtained coatings of hydroxyapatite were studied by Raman spectroscopy and XRD structural analysis. The results of XRD phase analysis showed the partial conversion of the hydroxyapatite phase to the α-tricalcium phosphate (α-TCP) phase during the detonation spraying process. The results obtained by Raman spectroscopy indicate that hydroxyapatite is the main phase in coatings. All hydroxyapatite-based coatings exhibited hydrophobic properties, which was confirmed by contact-angle values above 90° in wettability tests, characteristic of hydrophobic surfaces. The adhesive strength of the coatings was measured by the scratch test method. Tribological tests were conducted using the ball-on-disk method under both dry conditions and in Ringer's solution. This approach enabled the evaluation of wear resistance and friction coefficient of the coatings in different environments, simulating both lubrication-free conditions and those resembling physiological environments.

Development of PCL/PVA/PCL Scaffold for Local Delivery of Calcium Fructoborate for Bone Tissue Engineering

Calcium fructoborate (CaFB) has gathered attention due to its boron and calcium content, both of which are known to support bone health, deposition and regeneration. Previous studies have shown that CaFB has a positive effect on bone health and has been proven to promote bone-like properties. In light of this information, a local CaFB delivering scaffold could improve bone regeneration in cases of bone tissue loss. This study aimed to design a layer-by-layer polymeric sponge capable of achieving controlled local delivery of CaFB to improve bone tissue healing. The dose-dependent effect of CaFB on the cell viability of the Saos-2 cell line was investigated in vitro. Layer by-layer structure of the polymeric scaffold supported controlled release of CaFB, with 33.9±7.4% released after 7 days of incubation. CaFB at 31.25 μg/mL concentration was able to improve Saos-2 cell viability up to 174.7±24.1% and 127.7±8.7% after 1 and 4 days of incubation. After 7 days of incubation CaFB treatment at concentrations of 250, 125, 62.5 and 31.25 μg/mL improved cell viability up to 194.3±47.7, 155.3±17.7, 149.4±5.4 and 132.5±13.3%. The polycaprolactone/polyvinyl alcohol/polycaprolactonen(PCL/PVA/PCL) scaffold supported the viability of cells for 7 days and was shown to be biocompatible. The results of this study showed that CaFB is a potential compound thatncan be locally delivered within a scaffold system to improve bone tissue regeneration.

Promotion of bone osteogenic and regeneration by resveratrol-derived carbon dots in inflammatory environments via a one-step hydrothermal method

In the context of bone fractures, local inflammation complicates the healing process, adversely affecting the recovery of bone defects. This inflammatory response impedes the regenerative potential of stem cells and induces the differentiation of macrophages into the M1 type, thereby inhibiting bone regeneration. To address this issue, we synthesized carbon dots (CDs) using resveratrol and citric acid. These CDs demonstrated excellent water solubility and retained the anti-inflammatory properties of resveratrol. In an inflammatory environment co-cultured with resveratrol carbon dots (RES-CDs), we observed a reduction in inflammatory factors such as iNOS and an increase in anti-inflammatory factors like CD206. Alkaline phosphatase (ALP) activity, Alizarin Red staining, and immunofluorescence assays indicated that MC3T3 cells produced more calcium nodules after co-culture with RES-CDs, along with enhanced expression of bone formation factors BMP-2 and ALP. Additionally, real-time polymerase chain reaction (qRT-PCR) and immunofluorescence analysis demonstrated that RES-CDs could induce bone tissue proliferation and differentiation by upregulating ALP, BMP-2, OCN, and OPN. In a rat cranial defect model, RES-CDs promoted tissue healing and bone proliferation at weeks 1 and 4 post-surgery. These findings underscore the potential of resveratrol carbon dots in promoting bone tissue healing while mitigating inflammation, thereby offering a promising approach for nanocomposite materials in tissue repair.

Deferoxamine Accelerates Mandibular Condylar Neck Fracture Early Bone Healing by Promoting Type H VesselProliferation.

Condylar fractures (CFs) are a common type of maxillofacial trauma, especially in adolescents. Conservative treatment of CF avoids the possible complications of surgical intervention, but prolongs the patient's suffering because of the requirement for extended intermaxillary fixation. Therefore, the development of a new strategy to accelerate the rate of fracture healing to shorten the period of conservative treatment is of great clinical importance. To investigate the potential of deferoxamine (DFO) in promoting the healing process of CF in adolescent mice. Thirty-two 4-week-old male C57BL/6J mice were randomly assigned to four groups: vehicle + sham group, vehicle + CF group, DFO + sham group and DFO + CF group. After constructing the mandibular CF model, mandibular tissue samples were collected respectively at 1, 2 and 4 weeks postoperatively. Radiographic and histomorphometric analyses were employed to assess bone tissue healing and vascular formation. Deferoxamine was observed to promote the early bone healing of fracture, both radiologically and histomorphometrically. Furthermore, this enhancement of condylar neck fracture healing was attributed to the upregulation of the hypoxia-inducible factor-1α (HIF-1α) signalling pathway while facilitating the formation of type H vessels. In addition, DFO did not produce significant effects on the condylar neck between vehicle + sham and DFO + sham group. The application of the HIF-1α inducer DFO can enhance type H vessels expansion thereby accelerating condylar neck fracture healing.

Magnesium based implants: Alloying and coating strategies for improvement in its biomechanical and biocorrosion properties

Magnesium (Mg) based materials show great promise as temporary implant applications owing to their biocompatibility and biodegradability. These characteristics remove the risk of subsequent surgery to extract the implant once the process of bone tissue healing is finished. Additionally, its density and elastic modulus are near to those of natural bone, thereby reducing the stress-shielding effect. Mg is mostly recognized for its osteoconductive abilities, which implies that it encourages the generation of fresh bone tissue. It also has antimicrobial properties, which lower the possibility of infections leading to implant failure. Moreover, the rapid bio-corrosion of pure Mg in the presence of physiological fluids is a serious concern. The implant's mechanical integrity deteriorates as a result of this corrosion before the surrounding tissue has completely recovered. To address these issues, this review focused on approaches, including alloying, the creation of composites, and surface coating, which can increase their biomechanical and bio-corrosion properties. In vitro analysis of biomechanical and bio-corrosion characteristics of newly manufactured Mg-based implant material is presented in this article. In addition to this application, a list of approved devices made from Mg-based material is highlighted. Furthermore, the present challenges and prospects for future research are also discussed.

Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection

Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.

Combining three-dimensionality and CaP glass-PLA composites: Towards an efficient vascularization in bone tissue healing

Bone regeneration often fails due to implants/grafts lacking vascular supply, causing necrotic tissue and poor integration. Microsurgical techniques are used to overcome this issue, allowing the graft to anastomose. These techniques have limitations, including severe patient morbidity and current research focuses on stimulating angiogenesis in situ using growth factors, presenting limitations, such as a lack of control and increased costs. Non-biological stimuli are necessary to promote angiogenesis for successful bone constructs. Recent studies have reported that bioactive glass dissolution products, such as calcium-releasing nanoparticles, stimulate hMSCs to promote angiogenesis and new vasculature. Moreover, the effect of 3D microporosity has also been reported to be important for vascularisation in vivo. Therefore, we used room-temperature extrusion 3D printing with polylactic acid (PLA) and calcium phosphate (CaP) based glass scaffolds, focusing on geometry and solvent displacement for scaffold recovery. Combining both methods enabled reproducible control of 3D structure, porosity, and surface topography. Scaffolds maintained calcium ion release at physiological levels and supported human mesenchymal stem cell proliferation. Scaffolds stimulated the secretion of vascular endothelial growth factor (VEGF) after 3 days of culture. Subcutaneous implantation in vivo indicated good scaffold integration and blood vessel infiltration as early as one week after. PLA-CaP scaffolds showed increased vessel maturation 4 weeks after implantation without vascular regression. Results show PLA/CaP-based glass scaffolds, made via controlled 3D printing, support angiogenesis and vessel maturation, promising improved vascularization for bone regeneration.

Rheological and osteogenic effect of Agaricus blazei Murill polysaccharides on composite hydrogels based on HPMC/graphene oxide – A preliminary study

This study aimed to prepare and preliminarily characterize the potential bone restorative effect of composite hydrogels based on hydroxypropylmethylcellulose (HPMC), graphene oxide (GO), and polysaccharides from Agaricus blazei Murill mushroom (PAb). The chemical composition and morphology of the biomaterials were analyzed using FTIR, XRD, SEM, and EDS. Rheological tests were conducted on the hydrogels to assess their flow properties for in vivo application and product stability. Cytotoxicity assays were performed using the GO (1 – 100 µg mL–1) against human neutrophils. Additionally, an in vivo tooth extraction test was carried out by applying HPMC hydrogels containing GO and PAb directly into the alveoli to enhance oral bone restoration. The rheological behavior of the hydrogels followed the Ostwald de Waele model (R² > 0.99), with flow index (n) values below 1.0, indicating a pseudoplastic behavior. Furthermore, the consistency index (k) values increased with the addition of GO and PAb, suggesting a more complex structure, and altered flow behavior at lower shear rates. In the MTT assay, GO exhibited low cytotoxicity towards human neutrophils, maintaining cell viability above 95.0 % even at high concentrations. For the in vivo study, a bisphosphonate-induced osteonecrosis model was used to assess bone tissue healing through macroscopic and radiographic analyses. A significant improvement was observed in the reduction of bone tissue loss in rats treated with the hydrogels compared to the negative control (ZA group). These findings indicate that composite hydrogels containing HMPC/GO/PAb have the potential to be used as biomaterials for mitigating bone loss.

Investıgatıon of the effects of treatment with enoxaparın sodıum and hyperbarıc oxygen therapy on the recovery of rats wıth achılles tendon rupture

PurposeIn this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture.MethodsThirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically.ResultsThe groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores.ConclusionOur study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.

Differential effects of clopidogrel and/or aspirin on the healing of tooth extraction wound bone tissue.

A multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines. 7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10mg/kg/d), aspirin (15mg/kg/d), clopidogrel (10mg/kg/d)+aspirin (15mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin). MicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05). Clopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

Comparative study between physiological healing vs. the use of platelet-rich fibrin at the time of bone and gingival tissue healing in lower third molar surgeries. Bibliographic Review

Comparative study between physiological healing vs. the use of platelet-rich fibrin at the time of bone and gingival tissue healing in lower third molar surgeries. Bibliographic Review

Investigation of the Effect of Local and Systemic Preoperative Dexamethasone Application on Bone Tissue Healing in Mandibular Bone Defects.

The aim of this study was to investigate the effect of locally and systemically delivered single-dose corticosteroid injections on bone tissue. A total of 84 Wistar albino rats were divided into 2 groups as local and systemic injection groups, and 2 groups as control and experiment among themselves. Before the procedure, dexamethasone was given to the experimental group and physiological saline was given to the control group. A defect was created in the jawbone. It was sacrificed on the third, seventh, and 40th days. The mandible bones of the sacrificed rats were removed and the healing of the bone tissue was examined histopathologically. No significant difference was observed in the tissue sections of the subjects sacrificed after 40 days. However, the increase in fibroblastic connective tissue and the number of osteoblasts were less in the experimental local groups that were sacrificed after 7 days compared with the control groups (P=0.040 and 0.041). Again, it was determined that there was a statistically significant decrease in the experimental local group compared with the experimental systemic group (P=0.040 and 0.004). It can be said that single-dose corticosteroid applications cause a delay in bone healing in the early period.

Effect of platelet-rich fibrin on the recovery after third molar surgery: A systematic review and meta-analysis

This meta-analysis aimed to elucidate the effects of platelet-rich fibrin (PRF) on the recovery of alveolar bone after surgical removal of the mandibular third molars.PubMed, Cochrane Library, Web of Science, and Embase databases were searched from the inception to February 2023 for relevant studies on the application of PRF after the extraction of impacted mandibular third molars, with the language limited to English. Literature screening was conducted by two independent researchers. The Cochrane risk-of-bias tool was adopted for quality evaluation, and Stata 15.0 was used for statistical analysis. A total of 33 randomized controlled trials were included in the present study. Following surgical removal of the mandibular third molars, 1139 tooth sockets were filled with PRF, while 1138 sockets were sutured after conventional saline irrigation. The meta-analyses showed that PRF can relieve pain [(RR 0.454; 95% CI 0.23, 0.891); (SMD −0.74; 95% CI −0.97, 0.52)], improve swelling (SMD −1.48; 95% CI −1.90, −1.06), alleviate trismus (SMD −0.35; 95% CI −0.51, −0.19), reduce dry socket (SMD −0.18; 95% CI −030, −0.05), and promote bone tissue healing (SMD 2.34; 95% CI 0.18, 4.51). The current study confirms that PRF can reduce some postoperative complications. Local application of PRF after lower third molar extraction is a viable method for relieving pain and swelling, reducing the incidence of dry socket and trismus, and increasing bone density. However, whether it can promote soft tissue healing remains unclear. For patients undergoing complicated surgical extraction, local application of PRF into the sockets might be a good option.

The effect of platelet-rich fibrin (PRF) versus freeze-dried bone allograft (FDBA) used in alveolar ridge preservation on the peri-implant soft and hard tissues: a randomized clinical trial

BackgroundThe effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants.MethodsIn this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran’s Q test.ResultsThere was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05).ConclusionsExcept for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions.Clinical trial registrationThe research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available at https://clinicaltrials.gov/ (NCT05005377).