scholarly journals Establishment of a Numerical Model to Design an Electro-Stimulating System for a Porcine Mandibular Critical Size Defect

2019 ◽  
Vol 9 (10) ◽  
pp. 2160 ◽  
Author(s):  
Hendrikje Raben ◽  
Peer W. Kämmerer ◽  
Rainer Bader ◽  
Ursula van Rienen
Keyword(s):  
Numerical Model ◽  
Critical Size ◽  
Healing Process ◽  
Low Frequency ◽  
Implant Design ◽  
Tissue Properties ◽  
Stimulation Parameters ◽  
Promising Therapeutic Approach ◽  
Stimulation System

Electrical stimulation is a promising therapeutic approach for the regeneration of large bone defects. Innovative electrically stimulating implants for critical size defects in the lower jaw are under development and need to be optimized in silico and tested in vivo prior to application. In this context, numerical modelling and simulation are useful tools in the design process. In this study, a numerical model of an electrically stimulated minipig mandible was established to find optimal stimulation parameters that allow for a maximum area of beneficially stimulated tissue. Finite-element simulations were performed to determine the stimulation impact of the proposed implant design and to optimize the electric field distribution resulting from sinusoidal low-frequency ( f = 20 Hz ) electric stimulation. Optimal stimulation parameters of the electrode length h el = 25 m m and the stimulation potential φ stim = 0.5 V were determined. These parameter sets shall be applied in future in vivo validation studies. Furthermore, our results suggest that changing tissue properties during the course of the healing process might make a feedback-controlled stimulation system necessary.

scholarly journals Preliminary in Vivo Evaluation of Bone Healing in Critical Size Bone Defects Implanted with an Injectable Calcium Phosphate Bone Cement (Osteopaste)

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Che Nor Zarida Che Seman ◽  
Zamzuri Zakaria ◽  
Zunariah Buyong ◽  
Mohd Shukrimi Awang ◽  
Ahmad Razali Md Ralib @ Md Raghib
Keyword(s):  
Calcium Phosphate ◽  
Bone Cement ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Size ◽  
Healing Process ◽  
Bone Defects ◽  
Calcium Phosphate Bone Cement ◽  
Rabbit Tibia

Introduction: A novel injectable calcium phosphate bone cement (osteopaste) has been developed. Its potential application in orthopaedics as a filler of bone defects has been studied. The biomaterial was composed of tetra-calcium phosphate (TTCP) and tricalcium phosphate (TCP) powder. The aim of the present study was to evaluate the healing process of osteopaste in rabbit tibia. Materials and method: The implantation procedure was carried out on thirty-nine of New Zealand white rabbits. The in vivo bone formation was investigated by either implanting the Osteopaste, Jectos or MIIG – X3 into a critical size defect (CSD) model in the proximal tibial metaphysis. CSD without treatment served as negative control. After 1 day, 6 and 12 weeks, the rabbits were euthanized, the bone were harvested and subjected for analysis. Results: Radiological images and histological sections revealed integration of implants with bone tissue with no signs of graft rejection. There was direct contact between osteopaste material and host bone. The new bone was seen bridging the defect. Conclusion: The result showed that Osteopaste could be a new promising biomaterial for bone repair and has a potential in bone tissue engineering.

Vasculogenic Potential of Porcine Endothelial Colony Forming Cells

2008 ◽  
Author(s):  
Sheeny K. Lan ◽  
Daniel N. Prater ◽  
Russell D. Jamison ◽  
David A. Ingram ◽  
Mervin C. Yoder ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Critical Size ◽  
Healing Process ◽  
Bone Defects ◽  
Form And Function ◽  
Endothelial Colony Forming Cells ◽  
Tissue Engineering Construct ◽  
And Function ◽  
Natural Healing

The natural healing process cannot restore form and function to critical size bone defects without the presence of a graft to support and guide tissue regeneration [1]. Critical size bone defects in humans are typically on the order of centimeters or larger [2]. Thus, a major limitation of synthetic grafts or bone tissue engineering constructs is the lack of vascularization to support cell viability after placement in vivo [3]. Cells that participate in bone regeneration, must reside within 150–200 microns of a blood supply in order to gain proper nutrients and to eliminate waste [4]. Consequently, a tissue engineering construct of a clinically relevant size cannot rely on diffusion for transport of nutrients and waste. Previous research has shown that blood vessels can infiltrate scaffolds, but the overall process is too slow to prevent death of cells located in the center of a construct [5].

scholarly journals Assessment of the Bone Healing Process Mediated by Periosteum-Derived Mesenchymal Stem Cells’ Secretome and a Xenogenic Bioceramic—An In Vivo Study in the Rabbit Critical Size Calvarial Defect Model

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3512
Author(s):  
Mindaugas Pranskunas ◽  
Egidijus Šimoliūnas ◽  
Milda Alksne ◽  
Victor Martin ◽  
Pedro Sousa Gomes ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Critical Size ◽  
Healing Process ◽  
Rabbit Model ◽  
Biological Response ◽  
Calvarial Bone ◽  
Tissue Repair And Regeneration ◽  
Tissue Healing ◽  
Bone Tissue Formation

The mesenchymal stem cell (MSC) secretome has been considered an innovative therapeutic biological approach, able to modulate cellular crosstalk and functionality for enhanced tissue repair and regeneration. This study aims to evaluate the functionality of the secretome isolated from periosteum-derived MSCs, from either basal or osteogenic-induced conditions, in the healing of a critical size calvarial bone defect in the rabbit model. A bioceramic xenograft was used as the vehicle for secretome delivery, and the biological response to the established biocomposite system was assessed by clinical, histological, histomorphometric, and microtomographic analysis. A comparative analysis revealed that the osteogenic-induced secretome presented an increased diversity of proteins, with emphasis on those related to osteogenesis. Microtomographic and histological morphometric analysis revealed that bioceramic xenografts implanted with secretomes enhanced the new bone formation process, with the osteogenic-induced secretome inducing the highest bone tissue formation. The application of the MSC secretome, particularly from osteogenic-induced populations, may be regarded as an effective therapeutic approach to enhance bone tissue healing and regeneration.

Effect of Osteoplasty with Bioactive Glass (S53P4) in Bone Healing - In vivo Experiment on Common European Rabbits (Oryctolagus cuniculus)

2018 ◽  
Vol 69 (2) ◽  
pp. 429-433
Author(s):  
Solyom Arpad ◽  
Cristian Trambitas ◽  
Ecaterina Matei ◽  
Eugeniu Vasile ◽  
Fodor Pal ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Bone Fractures ◽  
Healing Process ◽  
Bone Grafts ◽  
Bone Substitutes ◽  
Native Bone ◽  
European Rabbits ◽  
Autologous Bone Grafts ◽  
Fracture Types

Osteoplasty, is a procedure mostly applied in complicated bone fractures. Nowadays this method is widely used in primary fracture treatment while the native bone graft is progressively replaced with various synthetic bone substitutes. From the numerous bone grafts we�d like to mention a representative of ceramics, the S53P4 bioactive glass. (BonAlive�). The aim of this study was to investigate the healing process of different fracture types generated on rabbit femurs. During this experiment we used seven common European rabbits. We separated these animals into two groups; in the first group we surgically generated a total fracture in the middle 1/3 of the femur, while in the second group, we produced only a bone defect on the femur. The osteoplasty was carried out with bioactive glass and autologous bone grafts. The radiographic follow-up was immediate after the operation and after 3, 6 and 7 weeks. The animals were euthanized after 19, 20 and 21 weeks, for histomorphometric examination of the femur. It was also studied the ionic release from the used bioactive glass at physiological pH and the etching of the glass was studied by Scanning Electron Microscopy.

Gene Silencing using siRNA for Preventing Liver Ischaemia-Reperfusion Injury

2018 ◽  
Vol 24 (23) ◽  
pp. 2692-2700 ◽  
Author(s):  
H. Susana Marinho ◽  
Paulo Marcelino ◽  
Helena Soares ◽  
Maria Luísa Corvo
Keyword(s):  
Gene Silencing ◽  
Reperfusion Injury ◽  
Therapeutic Potential ◽  
Major Complication ◽  
Ischaemia Reperfusion Injury ◽  
Small Interference Rna ◽  
Ischaemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Sirna Therapy

Background: Ischaemia-reperfusion injury (IRI), a major complication occurring during organ transplantation, involves an initial ischemia insult, due to loss of blood supply, followed by an inflammation-mediated reperfusion injury. A variety of molecular targets and pathways involved in liver IRI have been identified. Gene silencing through RNA interference (RNAi) by means of small interference RNA (siRNA) targeting mediators of IRI is a promising therapeutic approach. Objective: This study aims at reviewing the use of siRNAs as therapeutic agents to prevent IRI during liver transplantation. Method: We review the crucial choice of siRNA targets and the advantages and problems of the use of siRNAs. Results: We propose possible targets for siRNA therapy during liver IRI. Moreover, we discuss how drug delivery systems, namely liposomes, may improve siRNA therapy by increasing siRNA stability in vivo and avoiding siRNA off-target effects. Conclusion: siRNA therapeutic potential to preclude liver IRI can be improved by a better knowledge of what molecules to target and by using more efficient delivery strategies.

Synthesis and Biological Evaluation of Scutellarein Alkyl Derivatives as Preventing Neurodegenerative Agents with Improved Lipid Soluble Properties

2019 ◽  
Vol 15 (7) ◽  
pp. 771-780
Author(s):  
He-Min Li ◽  
Ting Gu ◽  
Wen-Yu Wu ◽  
Shao-Peng Yu ◽  
Tian-Yuan Fan ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Neuronal Damage ◽  
Thiobarbituric Acid ◽  
Rat Hepatocytes ◽  
Biological Evaluation ◽  
Thiobarbituric Acid Reactive Substance ◽  
Alkyl Derivatives ◽  
Promising Therapeutic Approach ◽  
Microsomal Membranes

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation. Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized. Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer. Results: This study indicated that compound 5e which had a benzyl group substituted at the C4'- OH position showed a potent antioxidant activity and good lipophilicity. Conclusion: 5e could be an effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

2021 ◽  
Vol 22 (8) ◽  
pp. 4087
Author(s):  
Maria Quitério ◽  
Sandra Simões ◽  
Andreia Ascenso ◽  
Manuela Carvalheiro ◽  
Ana Paula Leandro ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
In Vitro Release ◽  
Peptide Hormone ◽  
Plga Nanoparticles ◽  
Wound Healing Process ◽  
Target Area ◽  
Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

scholarly journals microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhou ◽  
Yang Lin ◽  
Xiuhua Kang ◽  
Zhicheng Liu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Extracellular Vesicles ◽  
Luciferase Assay ◽  
Therapeutic Effects ◽  
Loss Of Function ◽  
Fibroblast Activation ◽  
Promising Therapeutic Approach

Abstract Background Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model. Methods In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1). Results BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1. Conclusion In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.

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