Bone Tissue Healing Research Articles

The response of human osteoblasts, epithelial cells, fibroblasts, macrophages and oral bacteria to nanostructured titanium surfaces: a systematic study.

Nanotopography modification is a major focus of interest in current titanium surface design; however, the influence of the nanostructured surface on human cell/bacterium behavior has rarely been systematically evaluated. In this study, a homogeneous nanofiber structure was prepared on a titanium surface (Nano) by alkali-hydrothermal treatment, and the effects of this Nano surface on the behaviors of human MG-63 osteoblasts, human gingival epithelial cells (HGECs) and human gingival fibroblasts (HGFs) were evaluated in comparison with a smooth titanium surface (Smooth) by polishing and a micro-rough titanium surface (Micro) by sandblasting and acid etching. In addition, the impacts of these different surface morphologies on human THP-1 macrophage polarization and Streptococcus mutans attachment were also assessed. Our findings showed that the nanostructured surface enhanced the osteogenic activity of MG-63 cells (Nano=Micro>Smooth) at the same time that it improved the attachment of HGECs (Nano>Smooth>Micro) and HGFs (Nano=Micro>Smooth). Furthermore, the surface with nanotexture did not affect macrophage polarization (Nano=Micro=Smooth), but did reduce initial bacterial adhesion (Nano<Smooth<Micro). These results suggest that the nanostructured titanium surface may promote bone and soft tissue healing, and thereby increase the success and survival of dental implants.

Platelet-rich plasma ameliorates senescence-like phenotypes in a cellular photoaging model

Platelet-rich plasma (PRP) is a portion of blood plasma enriched with platelets widely investigated for accelerating bone and soft tissue healing.

Endoscopic surgery in the treatment of patients with extensive odontogenic cysts

The aim of the study was the assessment of effectiveness of endoscopic techniques in the treatment of extensive odontogenic cysts. Endosurgery for diagnostic and therapeutic purposes was used in 67 patients with odontogenic cysts of the jaws: 23 follicular cysts, 19 radicular cysts, 6 residual cysts, and 19 keratokists. The results prove that the developed methods of endovideosurgery of odontogenic cysts have low invasiveness, provide an optimal healing of bone tissue and reduce postoperative complications.

The effect of zinc oxide based sealer on bone defects healing

Summary Introduction Obturation as the final phase of endodontic treatment aims to provide complete hermetic filling along the entire length of the canal system from the coronal opening to the apical end. The aim of this study was to evaluate histological response of bone tissue on the implantaton of zinc oxide based material in artificially prepared defect in the mandible of rats. Material and method For the experiment, sixteen male Wistar rats were used. Using sterile steel burs a defect was made in mandible, between the midline and mental foramen. Zinc oxide based sealer was implanted in the defects of experimental group while the defects of control group healed spontaneously. One half of animals in both groups were sacrificed after thirty days, and the second half after ninety days. Microscopic preparations consisted of the defect with surrounding bone and after processing were analysed using light microscopy. Results The thirtieth day after implantation of the material, fibrovascular connective tissue was noted, with scant chronic inflammatory cell infiltrate. Away from the experimentally made defect, in the depth of the bone, lamellar bone with well-formed larger osteons was noted as well as enlarged Volkmann and Haversian canals. Ninety days after implantation of the material, there was no restitutio ad integrum, but intense focal remodelling of bone tissue was noted. Conclusion Endomethasone N slowed down bone tissue healing process by showing the signs of prolonged inflammation in bone tissue in which it has been implanted. Extension of the healing process is reflected in the slow replacement of fibrovascular connective tissue with newly formed bone tissue.

FABRICATION AND CHARACTERIZATION OF PCL/HA/PPY COMPOSITE SCAFFOLD USING FREEZE-DRYING TECHNIQUE

Bone tissue regeneration and healing could be notably quickened via applying electrical stimuli in the defected area. Hence, a conductive tissue engineering scaffold that is capable of delivering the electrical stimuli is greatly desirable. In this study, electrically conductive scaffold was fabricated by using a biocompatible conductive polymer, polypyrrole (PPY) in the optimized nanocomposite scaffold of Polycaprolactone (PCL) and Hydroxyapatite (HA) using freeze–drying technique. The scaffolds were evaluated by using a number of techniques. The morphology of the scaffolds was observed and analyzed using a scanning electron microscope (SEM). Composite scaffolds with suitable pore size distribution were obtained by freezing the polymer solution mixture at -18ºC, by controlling the polymer and solvent phase crystallization. The results showed that the average pore sizes were decreased from 123.7μm for PCL scaffolds to 91.6μm with the incorporation of HA nanoparticles. Electrical conductivity of the scaffolds was evaluated using a digital multimeter. The wettability and porosity of the scaffolds were increased with the incorporation of Polypyrrole than Polycaprolactone scaffold. The newly fabricated PCL/HA/PPY scaffold showed good prospect to be employed for bone tissue engineering applications.

Fabrication and evaluation of silica-based ceramic scaffolds for hard tissue engineering applications

In recent decades, bone scaffolds have received a great attention in biomedical applications due to their critical roles in bone tissue regeneration, vascularization, and healing process. One of the main challenges of using scaffolds in bone defects is the mechanical strength mismatch between the implant and surrounding host tissue which causes stress shielding or failure of the implant during the course of treatment. In this paper, space holder method was applied to synthesize diopside/forsterite composite scaffolds with different diopside content. During the sintering process, NaCl, as spacer agent, gradually evaporated from the system and produced desirable pore size in the scaffolds. The results showed that adding 10wt.% diopside to forsterite can enormously improve the bioactivity, biodegradability, and mechanical properties of the composite scaffolds. The size of crystals and pores of the obtained scaffolds were measured to be in the range 70–100nm and 100–250μm, respectively. Composite scaffolds containing 10wt.% diopside showed similar compressive strength and Young's modulus (4.36±0.3 and 308.15±7MPa, respectively) to that of bone.

Mesenchymal stem cell growth on and mechanical properties of fibrin-based biomimetic bone scaffolds.

Using the microenvironment of healing bone tissue as inspiration, this study utilized fibrin hydrogels combined with collagen type I and calcium phosphate ceramics to create a biomimetic bone scaffold. The contribution each component had on the growth of mesenchymal stem cells (hMSC) was assessed, and changes in the scaffold's mechanical properties were measured by indentation testing. The results show cell growth was greatest in scaffolds with lower concentrations of fibrinogen complex and followed a similar trend with the addition of collagen. However, cell growth was greatest in fibrin scaffolds with high concentrations of fibrinogen complex when combined with hydroxyapatite-β-tricalcium phosphate. The fibrin scaffold's stiffness does not significantly change over time, but the addition of collagen to scaffolds with low concentrations of fibrinogen complex had significant increases in stiffness by day 14. These results demonstrate that hMSC do not rapidly degrade fibrin and fibrin-collagen scaffolds in vitro. The data reported here can aid in the design and fabrication of fibrin-based engineered tissues and cell delivery vehicles that promote hMSC growth and viability as well as meet the mechanical requirements of native tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2945-2953, 2016.

Percutaneous ultrasound-guided dry needling (+/− injection) for varying musculoskeletal problems

Purpose: Dry needling involves the passing of a fine needle underneath the skin into either a muscle or tendon creating a calculated injury, triggering an inflammatory response and reparative tissue. While the procedure has existed for some time, evidence of its efficacy in the literature is sparse. There are several other treatment modalities such as corticosteroid injection, extracorporeal shockwave therapy, plantar iontophoresis with similar principles of bringing different growth factors and cytokines, stimulating bone and soft tissue healing.

Platelet-rich plasma promotes the migration and invasion of synovial fibroblasts in patients with rheumatoid arthritis

Platelet-rich plasma (PRP) is blood plasma that has been enriched with platelets, and the number of platelets is correlated with rheumatoid activity. PRP is a concentrated source of autologous platelets, and contains several different growth factors and cytokines, including platelet‑derived growth factor, transforming growth factor‑β and insulin‑like growth factor‑1, which stimulate healing of bone and soft tissue. Rheumatoid arthritis (RA) is characterized by synovial hyperplasia, cell activation, articular inflammation and invasion of the synovium into the adjacent bone and cartilage. The adhesion of fibroblast‑like synoviocytes (FLSs) onto the extracellular matrix (ECM), migration and invasion are important for the erosion and destruction of the articular cartilage of patients with RA. The aim of the present study was to investigate the effects of PRP on the adhesion, migration and invasion of RA‑FLSs. Scratch and Transwell migration assays determined that PRP at a concentration of 2 and 5% significantly enhanced the migration ability of RA‑FLSs. Treatment of RA‑FLSs with 2and 5% PRP promoted the adhesion and invasion of the cells. Additionally, the immunofluorescence assay revealed that PRP induced a decrease in the number of centrally located stress fibers and led to an increase in the formation of filopodia and lamellipodia in the detectable leading edge protrusions in RA‑FLSs. In addition, reverse transcription‑quantitative polymerase chain reaction and western blot analysis determined that PRP upregulated the protein and mRNA expression levels of matrix metalloproteinase‑1 (MMP‑1). In conclusion, the promotion of RA‑FLS cell migration, invasion and adhesion on the ECM by PRP may be modulated through the upregulation of MMP‑1 expression and the induction of actin cytoskeletal reorganization.

Treatment of bisphosphonate-related osteonecrosis of the jaw using platelet-rich fibrin

Background: Bisphosphonates are commonly prescribed antiresorptive agents for the management of patients with osteoporosis, Paget’s disease, multiple myeloma, and metastatic tumors. Platelet-rich fibrin (PRF) is a second generation platelet concentrate, and has the ability of regulating the inflammation and stimulation of chemotactic agents. The aim of this report is to present the treatment of Stage-3 bisphosphonate-related osteonecrosis of the jaw (BRONJ) by PRF.Clinical Presentation: A 77-year-old male patient with Stage-3 BRONJ was treated with minimal surgical operations and PRF membrane. The patient was followed up for 18 months, and there was no recurrence or exposure.Conclusion: PRF may promote the healing of both bone and soft tissues even in Stage-3 patients. This technique is an alternative treatment modality for the closure of bone exposure and tissue healing in BRONJ patients.

Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study.

BackgroundArginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25%) is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health.ObjectiveThe aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats.MethodsThe rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation.ResultsOsteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05). New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05). However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05).ConclusionASI supplementation significantly improved bone tissue healing in rats with critical-sized defects. This study demonstrated that ASI can enhance bone repair and has potential as a therapeutic regimen in humans.

Prediction of the intramembranous tissue formation during perisprosthetic healing with uncertainties. Part 2. Global clinical healing due to combination of random sources

This work proposes to examine the variability of the bone tissue healing process in the early period after the implantation surgery. The first part took into account the effect of variability of individual biochemical factors on the solid phase fraction, which is an indicator of the quality of the primary fixation and condition of its long-term behaviour. The next issue, addressed in this second part, is the effect of cumulative sources of uncertainties on the same problem of a canine implant. This paper is concerned with the ability to increase the number of random parameters to assess the coupled influence of those variabilities on the tissue healing. To avoid an excessive increase in the complexity of the numerical modelling and further, to maintain efficiency in computational cost, a collocation-based polynomial chaos expansion approach is implemented. A progressive set of simulations with an increasing number of sources of uncertainty is performed. This information is helpful for future implant design and decision process for the implantation surgical act.

Transcriptomic Changes in Osteoblasts Following Endothelial Cell-Cocultivation Suggest a Role of Extracellular Matrix in Cellular Interaction.

Vascularization is important for bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1,004 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. The microarray data could be confirmed by performing quantitative real time RT-PCR on selected genes. Furthermore, we could show that the ECM produced by HUVECs increased the expression of the osteogenic differentiation marker alkaline phosphatase (ALP) in hOBs. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction. J. Cell. Biochem. 117: 1869-1879, 2016. © 2016 Wiley Periodicals, Inc.

Minimally invasive osteosynthesis of distal tibial fractures using anterolateral locking plate: Evaluation of results and complications

PurposeSoft tissue healing is of paramount importance in distal tibial fractures for a successful outcome. There is an increasing trend of using anterolateral plate due to an adequate soft tissue cover on anterolateral distal tibia. The aim of this study was to evaluate the results and complications of minimally invasive anterolateral locking plate in distal tibial fractures. MethodsThis is a retrospective study of 42 patients with distal tibial fractures treated with minimally invasive anterolateral tibial plating. This study evaluates the bone and soft tissue healing along with emphasis on complications related to bone and soft tissue healing. ResultsFull weight bearing was allowed in mean time period of 4.95 months (3–12 months). A major local complication of a wound which required revision surgery was seen in one case. Minor complications were identified in 9 cases which comprised 4 cases of marginal necrosis of the surgical wound, 1 case of superficial infection, 1 case of sensory disturbance over the anterolateral foot, 1 case of muscle hernia and 2 cases of delayed union. Mean distance between the posterolateral and anterolateral incision was 5.7 cm (4.5–8 cm). ConclusionThe minimally invasive distal tibial fixation with anterolateral plating is a safe method of stabilization. Distance between anterolateral and posterolateral incision can be placed less than 7 cm apart depending on fracture pattern with proper surgical timing and technique.

Release of adenosine from chitosan beads

Event Abstract Back to Event Release of adenosine from chitosan beads Allen Jed Mamaril1, Parwinder Singh1, Ravi Patel1, Joel D. Bumgardner1 and Jessica A. Jennings1 1 University of Memphis, Department of Biomedical Engineering, United States Introduction: As many as 27 million American suffer from the painful chronic condition of osteoarthritis[1]. Most treatments are geared toward symptom management, but recent advancements in tissue engineering aim to heal articular cartilage. Recent literature has shown that adenosine reduces inflammation, increases proliferation and matrix production, and promotes chondrocyte growth in osteoarthritic models[2],[3]. This study was conducted to demonstrate efficacy of chitosan microbeads as a delivery vehicle for adenosine. Methods: Chitosan (Chitopharm S) solutions (2% w/v) were created by dissolving 3 or 6 mg/mL adenosine base powder (MP Biomedicals) in 2% acetic acid, adding chitosan and stirring overnight. An emulsion was created by stirring the solution with an impeller at a setting of 2000 rpm in a 1:1 mixture of light to heavy chain mineral oil and 1% Span 80. Glyoxal was added at 0.5% to the emulsion and the mixture was heated at 70°C while impelling for 24 hours. Microbeads were recovered by centrifugation and washing with hexanes, methanol, and then acetone. Four separate samples of dried beads weighing 50 mg were added to 1 mL sterile DMEM/High-glucose and vortexed. Eluate samples were taken every day for 7 days after vortexing and centrifugation. Adenosine concentration was measured with high performance liquid chromatography and normalized to known standard concentrations. Results: Higher concentrations of adenosine were observed in the elution samples collected over the first two days of the trial, with a peak elution of 1360 μg/ml on day two of elution for 6mg/ml concentration (Figure 1). The presence of adenosine in elution samples declined constantly over the next five days in a first-order release pattern for both loading concentrations. Discussion: Injectable chitosan microbeads deliver controlled amounts of adenosine over time, which offers advantages for drug delivery systems directed toward cartilage repair. By altering adenosine concentration in microbeads, elution profile and duration of the drug release can be controlled. Since previous studies have shown highest bioactivity of adenosine in the range of 50-200 µg/ml[2], loading with the lower amount may have improved therapeutic effect over the high-dose loaded microbeads. Evaluation of adherence of adenosine-loaded microbeads to damaged tissue as well as testing efficacy in promoting cell growth through in vitro chondrocyte cell culture and preclinical models will provide insight into the refinement of functional delivery systems. Conclusions: Adenosine-loaded microbeads may provide effective controlled delivery of bioactive adenosine for applications in promoting healing of cartilage, skin, bone, and soft tissues. Minimally invasive delivery, inexpensive cost, and biocompatibility may offer an advantage of adenosine-loaded chitosan microbeads over other treatment options for tissue repair, such as surgical procedures, joint replacement, and growth factor therapy. FedEx Institute of Technology Innovation Fund; Herff College of Engineering

Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study

Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg−1 of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

Green laser light irradiation enhances differentiation and matrix mineralization of osteogenic cells

Background and objectiveLow level laser therapy (LLLT) in both infrared and visible light is a therapeutic tool ever more proposed in clinical practice in different fields. The effect of near infrared LLLT has been described in a growing number of scientific publications related to bone tissue healing, both in vitro and in vivo. More recently, green visible light using potassium-titanyl-phosphate KTiOPO4 (KTP, 532nm) laser has been proposed in dermatology, urology, oral and maxillofacial surgery but has never been tested on bone tissue. The aim of the present work was to perform a preliminary in vitro study to analyze the effects of KTP laser, on the osteogenic differentiation of bone marrow stromal cells (BMSCs). Materials and methodsUsing a power meter the first step of this study aimed to evaluate the real power emitted by the KTP laser device and the amount of energy absorbed by culture medium and plastic in order to calculate the appropriate irradiation parameters for cultured cells. Primary bone marrow stromal cells prepared from C57BL/6 mice were cultured and induced to differentiate in the osteogenic lineage in the presence or in the absence of KTP LLLT at a fluence of 4J/cm2 three times a week. Specific staining of the cells and the extracellular matrix, microscopic analysis as well as quantitative RT-PCR were used to assess cell proliferation and differentiation. ResultsWe show here that KTP LLLT enhances the osteogenic differentiation of bone marrow stromal cells and the mineralization of their extracellular matrix. ConclusionOur results highlight that this LLLT experimental protocol with green light (KTP, 532nm) at 4J/cm2 has a positive effect on the osteogenic differentiation of murine bone marrow stromal cells. These preliminary results could be used as a basis to further investigate the effect of this KTP laser protocol on bone tissue engineering models in vivo and in vitro.

Early bone response to machined, sandblasting acid etching (SLA) and novel surface-functionalization (SLAffinity) titanium implants: characterization, biomechanical analysis and histological evaluation in pigs.

The purpose of the present study was to examine early tissue response and osseointegration in the animal model. The surface morphologies of SLAffinity were characterized using scanning electron microscopy and atomic force microscopy. The microstructures were examined by X-ray diffraction, and hardness was measured by nanoindentation. Moreover, the safety and toxicity properties were evaluated using computer-aided programs and cell cytotoxicity assays. In the animal model, implants were installed in the mandibular canine-premolar area of 12 miniature pigs. Each pig received three implants: machine, sandblasted, large grit, acid-etched, and SLAffinity-treated implants. The results showed that surface treatment did affect bone-to-implant contact (BIC) significantly. At 3 weeks, the SLAffinity-treated implants were found to present significantly higher BIC values than the untreated implants. The SLAffinity treatments enhanced osseointegration significantly, especially at early stages of bone tissue healing. As described above, the results of the present study demonstrate that the SLAffinity treatment is a reliable surface modification method.

Evaluation of Bone Healing After Osteotomies Prepared With Er:YAG Laser in Contact and Noncontact Modes and Piezosurgery—An Animal Study

To analyze the healing of bone tissue treated with Er:YAG laser contact and noncontact modes of and piezosurgery in a rat model using triangular laser profilometry. Twenty-four 10-week-old adult male Wistar rats were used in the study. Three osteotomies on the medial part of tibia were performed in each animal, 1 in the right tibia and 2 in the left tibia. The osteotomies were performed with a piezoelectric device set at maximal power and the Er:YAG laser in contact mode (power, 7.5 W; pulse energy, 375 mJ; repetition rate, 20 Hz; MSP mode) and noncontact mode (power, 7.5 W; pulse energy, 750 mJ; repetition rate, 10 Hz; QSP mode) with a novel type of circular, digitally controlled handpiece (x-Runner). After surgery, 6 animals were immediately euthanized (group 1), and the others were euthanized after 1 week (group 2, n = 6), 2 weeks (group 3, n = 6), and 3 weeks (group 4, n = 6). Bone healing after osteotomy was analyzed using a 3-dimensional laser scanning technique (ie, laser triangulation profilometry). The volume reduction rates are similar for all 3 techniques (0.2 to 0.25 mm(3) per week). Greater volume reduction of 0.25 mm3 per week was observed for the Er:YAG laser in noncontact mode (x-Runner). After 3 weeks, almost complete healing of the prepared osteotomy was observed. Within the limitations of this study, the osteotomies performed by the Er:YAG laser in digitally controlled noncontact mode healed the fastest.

Preventive Strategies for Patients at Risk of Medication-related Osteonecrosis of the Jaw.

For patients at risk of osteonecrosis of the jaw (ONJ), information can be provided by the pharmaceutical manufacturer, pharmacist, prescribing physician, dentist, and oral and maxillofacial surgeon. Prevention strategies to reduce the incidence of osteonecrosis should be applied as soon as it is determined that a patient will be placed on antiresorptive medication. Proper screening involves a comprehensive oral examination with radiographs followed by oral hygiene instruction and necessary dental treatment; surgical techniques and adjunctive therapies that favor optimum healing of bone and soft tissue decrease the risk of ONJ. No dental procedures are absolutely contraindicated.