scholarly journals Free Transplantation of a Tissue Engineered Bone Graft into an Irradiated, Critical-Size Femoral Defect in Rats

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2256
Author(s):  
Ulrike Rottensteiner-Brandl ◽  
Ulf Bertram ◽  
Lara F. Lingens ◽  
Katrin Köhn ◽  
Luitpold Distel ◽  
...  
Keyword(s):  
Bone Healing ◽  
Bone Defects ◽  
Severe Trauma ◽  
In Vivo Studies ◽  
Term Survival ◽  
Femoral Defect ◽  
Custom Made ◽  
Healing Tissue ◽  
Large Bone

Healing of large bone defects remains a challenge in reconstructive surgery, especially with impaired healing potential due to severe trauma, infection or irradiation. In vivo studies are often performed in healthy animals, which might not accurately reflect the situation in clinical cases. In the present study, we successfully combined a critical-sized femoral defect model with an ionizing radiation protocol in rats. To support bone healing, tissue-engineered constructs were transferred into the defect after ectopic preossification and prevascularization. The combination of SiHA, MSCs and BMP-2 resulted in the significant ectopic formation of bone tissue, which can easily be transferred by means of our custom-made titanium chamber. Implanted osteogenic MSCs survived in vivo for a total of 18 weeks. The use of SiHA alone did not lead to bone formation after ectopic implantation. Analysis of gene expression showed early osteoblast differentiation and a hypoxic and inflammatory environment in implanted constructs. Irradiation led to impaired bone healing, decreased vascularization and lower short-term survival of implanted cells. We conclude that our model is highly valuable for the investigation of bone healing and tissue engineering in pre-damaged tissue and that healing of bone defects can be substantially supported by combining SiHA, MSCs and BMP-2.

scholarly journals Vascularization of Nanohydroxyapatite/Collagen/Poly(L-lactic acid) Composites by Implanting Intramuscularly In Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Hai Wang ◽  
Xiao Chang ◽  
Guixing Qiu ◽  
Fuzhai Cui ◽  
Xisheng Weng ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Orthopaedic Surgery ◽  
Bone Substitutes ◽  
Bone Defects ◽  
Large Defect ◽  
Natural Bone ◽  
Composition And Structure ◽  
Large Bone ◽  
Large Bone Defects

It still remains a major challenge to repair large bone defects in the orthopaedic surgery. In previous studies, a nanohydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composite, similar to natural bone in both composition and structure, has been prepared. It could repair small sized bone defects, but they were restricted to repair a large defect due to the lack of oxygen and nutrition supply for cell survival without vascularization. The aim of the present study was to investigate whether nHAC/PLA composites could be vascularized in vivo. Composites were implanted intramuscularly in the groins of rabbits for 2, 6, or 10 weeks (n=5×3). After removing, the macroscopic results showed that there were lots of rich blood supply tissues embracing the composites, and the volumes of tissue were increasing as time goes on. In microscopic views, blood vessels and vascular sprouts could be observed, and microvessel density (MVD) of the composites trended to increase over time. It suggested that nHAC/PLA composites could be well vascularized by implanting in vivo. In the future, it would be possible to generate vascular pedicle bone substitutes with nHAC/PLA composites for grafting.

Hydroxyapatite scaffold pore architecture effects in large bone defects in vivo

2013 ◽  
Vol 28 (7) ◽  
pp. 1016-1027 ◽  
Author(s):  
Teja Guda ◽  
John A Walker ◽  
Brian Singleton ◽  
Jesus Hernandez ◽  
Daniel S Oh ◽  
...  
Keyword(s):  
Bone Defects ◽  
Pore Architecture ◽  
Hydroxyapatite Scaffold ◽  
Large Bone ◽  
Large Bone Defects

scholarly journals 3D Biomimetic Porous Titanium (Ti6Al4V ELI) Scaffolds for Large Bone Critical Defect Reconstruction: An Experimental Study in Sheep

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1389 ◽  
Author(s):  
Alberto Maria Crovace ◽  
Luca Lacitignola ◽  
Donato Monopoli Forleo ◽  
Francesco Staffieri ◽  
Edda Francioso ◽  
...  
Keyword(s):  
Bone Defects ◽  
Porous Titanium ◽  
Control Group ◽  
Large Animal ◽  
Sintered Titanium ◽  
Porous Hydroxyapatite ◽  
X Ray ◽  
Custom Made ◽  
Critical Defect ◽  
Large Bone

The main goal in the treatment of large bone defects is to guarantee a rapid loading of the affected limb. In this paper, the authors proposed a new reconstructive technique that proved to be suitable to reach this purpose through the use of a custom-made biomimetic porous titanium scaffold. An in vivo study was undertaken where a complete critical defect was experimentally created in the diaphysis of the right tibia of twelve sheep and replaced with a five-centimeter porous scaffold of electron beam melting (EBM)-sintered titanium alloy (EBM group n = 6) or a porous hydroxyapatite scaffold (CONTROL group, n = 6). After surgery, the sheep were allowed to move freely in the barns. The outcome was monitored for up to 12 months by periodical X-ray and clinical examination. All animals in the CONTROL group were euthanized for humane reasons within the first month after surgery due to the onset of plate bending due to mechanical overload. Nine months after surgery, X-ray imaging showed the complete integration of the titanium implant in the tibia diaphysis and remodeling of the periosteal callus, with a well-defined cortical bone. At 12 months, sheep were euthanized, and the tibia were harvested and subjected to histological analysis. This showed bone tissue formations with bone trabeculae bridging titanium trabeculae, evidencing an optimal tissue-metal interaction. Our results show that EBM-sintered titanium devices, if used to repair critical bone defects in a large animal model, can guarantee immediate body weight-bearing, a rapid functional recovery, and a good osseointegration. The porous hydroxyapatite scaffolds proved to be not suitable in this model of large bone defect due to their known poor mechanical properties.

Cell-Based Therapy by Implanted Human Bone Marrow-Derived Mononuclear Cells Improved Bone Healing of Large Bone Defects in Rats

2015 ◽  
Vol 21 (9-10) ◽  
pp. 1565-1578 ◽  
Author(s):  
Caroline Seebach ◽  
Dirk Henrich ◽  
Alexander Schaible ◽  
Borna Relja ◽  
Manfred Jugold ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Mononuclear Cells ◽  
Bone Defects ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cell Based Therapy ◽  
Large Bone ◽  
Large Bone Defects

scholarly journals Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018

2019 ◽  
pp. 1-16
Author(s):  
Ismail Hadisoebroto Dilogo ◽  
Jessica Fiolin
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Bone Regeneration ◽  
Conditioned Medium ◽  
Bone Healing ◽  
In Vitro Studies ◽  
In Vivo Studies

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome. Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018 Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis. Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review. Results: Three tables of studies were constructed for in vitro studies and in-vivo studies. Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.

scholarly journals Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 390 ◽  
Author(s):  
Flavia Resende Diniz ◽  
Romerito Cesar A. P. Maia ◽  
Lucas Rannier Andrade ◽  
Luciana Nalone Andrade ◽  
Marco Vinicius Chaud ◽  
...  
Keyword(s):  
Wound Healing ◽  
Silver Nanoparticles ◽  
Sodium Alginate ◽  
Time Course ◽  
In Vivo Studies ◽  
Natural Polymers ◽  
Cutaneous Lesions ◽  
Cutaneous Wounds ◽  
Healing Tissue

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430–450 nm in the ultraviolet-visible (UV–Vis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FT–IR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm−1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.

scholarly journals Experimental model of chronic focal osteomyelitis for in vivo studies

2021 ◽  
Vol 10 (1) ◽  
pp. 71-77
Author(s):  
V.N. Mitrofanov ◽  
◽  
O.P. Zhivtsov ◽  
N.Yu. Orlinskaya ◽  
D.V. Davydenko ◽  
...  
Keyword(s):  
Experimental Model ◽  
Chronic Osteomyelitis ◽  
Dynamic Assessment ◽  
Infectious Agent ◽  
Bone Defects ◽  
Surgical Debridement ◽  
In Vivo Studies ◽  
Material Research ◽  
Experimental Animals

Introduction. The article describes an experimental model of chronic suppurative osteomyelitis in a rabbit. As new therapeutic and diagnostic algorithms for the supervision of patients with osteomyelitis appear, there is an growing need to compare the methods of surgical debridement and plasty of bone defects in an infectious process, in order to create experimental standardized pathological conditions as close to the clinical course of the disease in humans as possible. The aim of the study was to develop an experimental model of a standardized chronic purulent bone cavity, suitable for a comprehensive assessment of surgical debridement effectiveness and osteoplastic properties of bone substitute materials. Materials and methods. A standardized defect of the tibia in 24 rabbits was formed. The Staphylococcusaureus strain was used as an infectious agent. A dynamic assessment of the main indicators of blood counts in animals was carried out. The formation of chronic osteomyelitis was evaluated using radiography, com-puted tomography methods and histological studies. Results. It was shown that purulent bone wound developed in experimental animals with the technique cre-ated, and a defect with signs of a chronic purulent-inflammatory process was demonstrated. Conclusion. The proposed model of chronic osteomyelitis is reproducible. Operational flexibility and identi-cal in size and location bone defects allow to use this model in new osteoplastic material research. Keywords: chronic osteomyelitis, experiment, experimental animals

scholarly journals Radiological and clinical outcomes using induced membrane technique combined with bone marrow concentrate in the treatment of chronic osteomyelitis of immature patients

2021 ◽  
Vol 10 (1) ◽  
pp. 31-40
Author(s):  
Jie Shen ◽  
Dong Sun ◽  
Shengpeng Yu ◽  
Jingshu Fu ◽  
Xiaohua Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Healing ◽  
Chronic Osteomyelitis ◽  
Young Patients ◽  
Bone Defects ◽  
Healing Time ◽  
Induced Membrane ◽  
Membrane Technique ◽  
Induced Membrane Technique ◽  
Large Bone

Aims Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones. Methods Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed. Results Patient infection in both groups was eradicated after IMT surgery. As for reconstruction surgery, no substantial changes in the operative period (p = 0.852), intraoperative blood loss (p = 0.573), or length of hospital stay (p = 0.362) were found between the two groups. All patients were monitored for 12 to 60 months. The median time to bone healing was 4.0 months (interquartile range (IQR) 3.0 to 5.0; range 3 to 7) and 5.0 months (IQR 4.0 to 7.0; range 3 to 10) in Groups BMCA and BMAA, respectively. The time to heal in Group BMCA versus Group BMAA was substantially lower (p = 0.024). Conclusion IMT with BMCA or BMAA may attain healing in large bone defects secondary to COM in children. The bone healing time was significantly shorter for BMCA, indicating that this could be considered as a new strategy for bone defect after COM treatment. Cite this article: Bone Joint Res 2021;10(1):31–40.

scholarly journals Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Wei Hu ◽  
Jia-Wu Liang ◽  
Song Liao ◽  
Zhi-Dong Zhao ◽  
Yu-Xing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Flow Cytometry ◽  
Genomic Stability ◽  
Bone Defects ◽  
Self Renewal ◽  
Femoral Defect ◽  
Tnf Α ◽  
Radiation Induced ◽  
Γ Ray

Abstract Background The healing of bone defects can be challenging for clinicians to manage, especially after exposure to ionizing radiation. In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing. Methods CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed. The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. Moreover, postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis. Results The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (P < 0.05). Melatonin maintained genomic stability, reduced postradiation CBSC apoptosis and intracellular oxidative stress, and enhanced expression of antioxidant-related enzymes (P < 0.05). Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels via the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. Melatonin was also found to exhibit antioxidant effects via NRF2 signaling. In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density values with lower IL-6 and TNF-α levels than in the irradiation and the Matrigel groups (P < 0.05). Conclusion This study suggested that melatonin could protect CBSCs against γ-ray radiation and assist in the healing of postradiation bone defects.

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