scholarly journals In vivo analysis of a proprietary glass-based adhesive for sternal fixation and stabilization using rabbit and sheep models

2021 ◽  
Vol 32 (5) ◽  
Author(s):  
Cina Mehrvar ◽  
Emily Deignan ◽  
Mark Hurtig ◽  
Gideon Cohen ◽  
Paul Zalzal ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Inflammatory Response ◽  
Rabbit Model ◽  
Median Sternotomy ◽  
Biological Response ◽  
Cadaver Study ◽  
Mechanical Tests ◽  
Sheep Model ◽  
Wire Cerclage

AbstractWire cerclage remains the standard method of care for sternal fixation, following median sternotomy, despite being beset with complications. An emerging treatment option has been to augment the wires with an adhesive. A patented ionomeric glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) has been used to formulate GPC+, a glass polyalkenoate cement (GPC), by mixing it with poly(acrylic) acid (PAA) and de-ionized water. In a human cadaver study, this material, when applied with wire cerclage, was able to significantly reduce sternal instability. However, the material has yet to be tested in pertinent animal models. Here, after a series of physical and mechanical tests to confirm suitability of the experimental material for implantation, three samples of GPC+ were implanted in either the tibia or femur of three different rabbits, alongside sham defects, for two different time modalities. A further seven samples of GPC+ and one poly(methyl methacrylate) control (PMMA) were implanted in either the tibia or femur of two different sheep. The sheep containing the PMMA was sacrificed at 8 weeks and the other at 16 weeks, to evaluate time dependent biological response. Upon sacrifice, microCT images were acquired and histology slides prepared for analysis. All three GPC+ samples implanted in the rabbit model, for the two time modalities, were characterized by minimal bone resorption along with a mild inflammatory response. Five of the seven GPC+ materials implanted in the sheep model (all three implanted for 8 weeks and two of those implanted for 16 weeks) were associated with mild to moderate immune response, comparable to that observed with PMMA, as well as mild bone resorption. The remaining two GPC + materials (implanted in the sheep model for 16 weeks) exhibited no bone resorption or inflammatory response and appeared to stimulate increased bone density at the implant site. These results suggest that GPC + can be a viable bone adhesive for use in hard tissue applications such as sternal fixation and stabilization.

scholarly journals Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

2021 ◽  
Vol 12 (3) ◽  
pp. 44
Author(s):  
Leyla Hasandoost ◽  
Daniella Marx ◽  
Paul Zalzal ◽  
Oleg Safir ◽  
Mark Hurtig ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Ct Images ◽  
Revision Total Knee Arthroplasty ◽  
Volumetric Shrinkage ◽  
Ion Release ◽  
Sheep Model ◽  
Cement Interface ◽  
Setting Times ◽  
Varied Response

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.

A brief overview on role of graphene based material in therapeutic management of inflammatory response signalling cascades

2020 ◽  
Vol 21 ◽  
pp. 25-36
Author(s):  
Ruchira Das ◽  
◽  
Priyanka Sow ◽  
Sudatta Dey ◽  
Asmita Samadder ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Water Solubility ◽  
Biomedical Application ◽  
Rapid Development ◽  
Graphene Quantum Dots ◽  
Biological Response ◽  
Vital Role ◽  
Therapeutic Management ◽  
In Vivo Models

Graphene is a novel, sp2 carbon atoms bonded, two-dimensional nano-material. Due to their favorable electronic, thermal, optical, and mechanical property, graphene and its derivatives, like graphene oxide (GO) and graphene quantum dots (GQDs) are used in widespread applications. The outstanding potentials of these compounds in the field of nanoelectronics, composite materials, sensors, energy technology etc helped in the rapid development in their functionalization, modulatory effects on various systems of our body. GQDs has been suggested as a new nanomaterial with improved biocompatibility, biodegradability, water solubility and considerably low cytotoxic effects in in vivo models, and are applicable for altering immune responses based on quantum confinement and edge effect properties. The review particularly elucidates the mechanistic approach by which graphene and/ or its derivatives and/ or their nano-compound aid in therapeutic management against myriads of immunological perspectives. GQDs have unique physiochemical properties with carbon sheets showcases out-standing biological response against immunological interventions by altering the activities of t-cell lymphocytes. On the contrary GO plays a vital role in eliciting inflammatory signaling factors by controlling proinflammation and an anti-inflammatory response. Therefore, this review shall help the readers to have an overview of the biomedical application of graphene and its derivatives to design target specific drugs to regulate the immune response based prognosis andcure.

Hybrid Chitosan Membranes Tested in Sheep for Guided Tissue Regeneration

2007 ◽  
Vol 361-363 ◽  
pp. 1265-1268 ◽  
Author(s):  
P.P. Cortez ◽  
Yuki Shirosaki ◽  
C.M. Botelho ◽  
M.J. Simões ◽  
F. Gartner ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Tissue Regeneration ◽  
Chitosan Solution ◽  
Clinical Applications ◽  
Histological Evaluation ◽  
Sheep Model ◽  
The Third ◽  
Chitosan Membranes

Previous in vitro studies confirmed an improved cytocompatibility of chitosan-silicate hybrid membranes over chitosan membranes. The main goal of this study was to assess the in vivo histocompatibility of both membranes through subcutaneous implantations at different time periods, 1 week, 1, 2 and 3 months, using a sheep model. Chitosan membranes elicited an exuberant inflammatory response and were consequently rejected. The hybrid chitosan membranes were not rejected and the degree of inflammatory response decreased gradually until the third month of implantation. Histological evaluation also showed that these membranes can be resorbed in vivo. This study demonstrates that the incorporation of silicate into the chitosan solution improves its histocompatibility, indicating that the hybrid chitosan-silicate membranes are suitable candidates to be used in clinical applications.

scholarly journals Selective Germline Genome Edited Pig Meninges Grafts for the Abdominal Wall Closure in Damage Control Surgery

2020 ◽  
Author(s):  
Lijin Zou ◽  
Youlai Zhang ◽  
Ying He ◽  
Hui Yu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Abdominal Wall ◽  
Damage Control ◽  
Abdominal Wall Reconstruction ◽  
Rabbit Model ◽  
Damage Control Surgery ◽  
Electrolyte Balance ◽  
Abdominal Wall Defects ◽  
Temporary Abdominal Closure

AbstractReconstruction of abdominal wall defects is still a big challenge in surgery, especially where there is insufficient fascia muscular or excessive tension of the defects in emergency and life-threatening scenarios. Indeed, the concept of damage control surgery has been advanced in the management of both traumatic and nontraumatic surgical settings. The strategy requires abridged surgery and quick back to intensive care units (ICU) for aggressive resuscitation. In the damage control laparotomy, patients are left with open abdomen or provisional closure of the abdomen with a planned return to the operating room for definitive surgery. So far, various techniques have been utilized to achieve early temporary abdominal closure, but there is no clear consensus on the ideal method or material for abdominal wall reconstruction. We recently successfully created the selective germline genome-edited pig (SGGEP) and here we aimed to explore the feasibility of in vivo reconstruction of the abdominal wall in a rabbit model with SGGEP meninges grafts (SGGEP-MGs). Our result showed that the SGGEP-MGs could restore the integrity of the defect very well. After 7 weeks of engraftment, there was no sign of herniation observed, the grafts were re-vascularized, and the defects were well repaired. Histologically, the boundary between the graft and the host was very well integrated and there was no strong inflammatory response. Therefore, this kind of closure could help restore the fluid and electrolyte balance and to dampen systemic inflammatory response in damge control surgery while ADM graft failed to establish re-vascularization as the same as the SGGEP-MG. It is concluded that the meninges of SGGEP could serve as a high-quality alternative for restoring the integrity of the abdominal wall, especially for damage control surgery.

scholarly journals NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

2021 ◽  
Vol 12 ◽  
Author(s):  
Na Jiang ◽  
Jinyang An ◽  
Kuan Yang ◽  
Jinjin Liu ◽  
Conghui Guan ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Osteoclast Differentiation ◽  
Inflammatory Factor ◽  
Inflammatory Microenvironment ◽  
Risk Of Death ◽  
Caspase 1

Osteoporosis is a systemic bone metabolism disease that often causes complications, such as fractures, and increases the risk of death. The nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an intracellular multiprotein complex that regulates the maturation and secretion of Caspase-1 dependent proinflammatory cytokines interleukin (IL)-1β and IL-18, mediates inflammation, and induces pyroptosis. The chronic inflammatory microenvironment induced by aging or estrogen deficiency activates the NLRP3 inflammasome, promotes inflammatory factor production, and enhances the inflammatory response. We summarize the related research and demonstrate that the NLRP3 inflammasome plays a vital role in the pathogenesis of osteoporosis by affecting the differentiation of osteoblasts and osteoclasts. IL-1β and IL-18 can accelerate osteoclast differentiation by expanding inflammatory response, and can also inhibit the expression of osteogenic related proteins or transcription factors. In vivo and in vitro experiments showed that the overexpression of NLRP3 protein was closely related to aggravated bone resorption and osteogenesis deficiency. In addition, abnormal activation of NLRP3 inflammasome can not only produce inflammation, but also lead to pyroptosis and dysfunction of osteoblasts by upregulating the expression of Caspase-1 and gasdermin D (GSDMD). In conclusion, NLRP3 inflammasome overall not only accelerates bone resorption, but also inhibits bone formation, thus increasing the risk of osteoporosis. Thus, this review highlights the recent studies on the function of NLRP3 inflammasome in osteoporosis, provides information on new strategies for managing osteoporosis, and investigates the ideal therapeutic target to treat osteoporosis.

scholarly journals Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair

Cartilage ◽  
2021 ◽  
pp. 194760352110354
Author(s):  
Zahra Abpeikar ◽  
Lida Moradi ◽  
Moosa Javdani ◽  
Saeid Kargozar ◽  
Mostafa Soleimannejad ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Antioxidant Capacity ◽  
Silk Fibroin ◽  
Rabbit Model ◽  
Mechanical Tests ◽  
Toxicity Tests ◽  
Self Healing ◽  
Composite Scaffolds ◽  
Meniscus Healing

Objective Meniscus injuries in the inner avascular zone have weak intrinsic self-healing capacity and often progress to osteoarthritis. This study focused on evaluating the effects of polycaprolactone/silk fibroin/gelatin/ascorbic acid (PCL/SF/Gel/AA) composite scaffolds seeded with adipose-derived mesenchymal stem cells (ASCs), in the meniscus repair. Design To this end, composite scaffolds were cross-linked using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride. Scaffolds were then characterized by scanning electron microscope, mechanical tests, total antioxidant capacity, swelling, and toxicity tests. Results The PCL/SF/Gel/AA scaffolds exhibited suitable mechanical properties. Furthermore, vitamin C rendered them the highest antioxidant capacity. The PCL/SF/Gel/AA scaffolds also showed good biocompatibility and proliferation for chondrocytes. Moreover, the PCL/SF/Gel/AA scaffold seeded with allogeneic ASCs was engrafted in New Zealand rabbits who underwent unilateral punch defect in the medial meniscus of the right knee. After 2 months postimplantation, macroscopic and histologic studies for new meniscus cartilage were performed. Conclusions Our results indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits.

scholarly journals In VitroCytokine Expression andIn VivoHealing and Inflammatory Response to a Collagen-Coated Synthetic Bone Filler

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Daniele Bollati ◽  
Marco Morra ◽  
Clara Cassinelli ◽  
Saturnino Marco Lupi ◽  
Ruggero Rodriguez y Baena
Keyword(s):  
Inflammatory Response ◽  
New Product Development ◽  
Rabbit Model ◽  
Negative Control ◽  
Synthetic Bone ◽  
Bone Filler ◽  
The Relationship ◽  
Intended Use

The goal of the present work was to investigate the relationship betweenin vivohealing and inflammatory response andin vitrocytokine expression by macrophages of a synthetic bone filler (25% hydroxylapatite-75%β-tricalcium phosphate) bearing a surface nanolayer of collagen. A clinically accepted, state-of-the-art xenograft material was used as a “negative control,” that is, as a material that provides the correct clinical response for the intended use.In vitrodata show that both materials exert a very low stimulation of proinflammatory cytokines by macrophages, and this was confirmed by the very mild inflammatory response detected inin vivotests of local response in a rabbit model. Also,in vitrofindings suggest a different mechanism of healing for the test and the control material, with a higher regenerative activity for the synthetic, resorbable filler, as confirmed byin vivoobservation and literature reports. Thus, the simplein vitromodel adopted provides a reasonable forecast ofin vivoresults, suggesting that new product development can be guided byin vitrotuning of cell-materials interactions.

scholarly journals A Composite Chitosan-Reinforced Scaffold Fails to Provide Osteochondral Regeneration

2019 ◽  
Vol 20 (9) ◽  
pp. 2227 ◽  
Author(s):  
Alice Roffi ◽  
Elizaveta Kon ◽  
Francesco Perdisa ◽  
Milena Fini ◽  
Alessandro Di Martino ◽  
...  
Keyword(s):  
Composite Scaffold ◽  
Rabbit Model ◽  
Immunohistochemical Analysis ◽  
Bone Scaffold ◽  
Sheep Model ◽  
Tissue Healing ◽  
Ability To Regenerate ◽  
Osteochondral Regeneration ◽  
Chitosan Composite

Several biomaterials have recently been developed to address the challenge of osteochondral regeneration. Among these, chitosan holds promises both for cartilage and bone healing. The aim of this in vivo study was to evaluate the regeneration potential of a novel hybrid magnesium-doped hydroxyapatite (MgHA), collagen, chitosan-based scaffold, which was tested in a sheep model to ascertain its osteochondral regenerative potential, and in a rabbit model to further evaluate its ability to regenerate bone tissue. Macroscopic, microtomography, histology, histomorphometry, and immunohistochemical analysis were performed. In the sheep model, all analyses did not show significant differences compared to untreated defects (p > 0.05), with no evidence of cartilage and subchondral bone regeneration. In the rabbit model, this bone scaffold provided less ability to enhance tissue healing compared with a commercial bone scaffold. Moreover, persistence of scaffold material and absence of integration with connective tissue around the scaffolds were observed. These results raised some concerns about the osteochondral use of this chitosan composite scaffold, especially for the bone layer. Further studies are needed to explore the best formulation of chitosan-reinforced composites for osteochondral treatment.

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.

The Effect of External Fixator Pin Geometry and Dynamic Loading on Bone Remodelling at the Pin-Bone Interface (PBI), in an In Vivo Sheep Tibia Model

1995 ◽  
Vol 08 (01) ◽  
pp. 14-24 ◽  
Author(s):  
J. F. Zaruby ◽  
J. B. Finlay ◽  
A. E. Valliant ◽  
M. B. Hurtig
Keyword(s):  
Bone Resorption ◽  
Dynamic Loading ◽  
External Fixator ◽  
Biological Response ◽  
Control Groups ◽  
Bone Interface ◽  
Treatment Groups ◽  
Pin Geometry ◽  
And Control

SummaryThe purpose of this study was to study the effects of pin design and dynamic loading on the biological response of bone at the pin-bone interface (PBI). An electro-pneumatic pin-loading device was used to mimic the forces that would be experienced by external fixator pins, during patient ambulation following repair of a fracture with external skeletal fixation. The remodelling response was assessed histologically with fluorescence microscopy of plasticembedded undecalcified pin-bone sections, and surface-stained histomorphometry.There were no significant differences between the AO Schanz and Howmedica Apex 5.0 mm diameter self-tapping pin designs when they were inserted in 4.5 mm diameter predrilled pilot holes. When pin type was controlled for, significant differences (p<0.05) existed between loaded and control groups as well as between entry (near) and exit (far) cortices. Less bone resorption was observed in the non-loaded group in comparison to the dynamically loaded group, and bone resorption in the near cortex consistently exceeded the amount of bone resorption in the far cortex for both treatment groups.The purpose of this study was to examine the effects of pin design and dynamic pin loading on the remodelling response of cortical bone at the pin-bone interface (PBI) of intact sheep tibiae. No significant differences were demonstrated between pin designs; however, significant differences (p<0.05) existed between loaded versus control pins, as well as between entry and exit cortices.

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