scholarly journals Combination of a Collagen Scaffold and an Adhesive Hyaluronan-Based Hydrogel for Cartilage Regeneration: A Proof of Concept in an Ovine Model

Cartilage ◽  
2021 ◽  
pp. 194760352198941
Author(s):  
Clara Levinson ◽  
Emma Cavalli ◽  
Brigitte von Rechenberg ◽  
Marcy Zenobi-Wong ◽  
Salim E. Darwiche
Keyword(s):  
Collagen Scaffold ◽  
Cartilage Regeneration ◽  
Repair Process ◽  
Single Step ◽  
Surrounding Tissue ◽  
Proof Of Concept ◽  
Ovine Model ◽  
Stifle Joint ◽  
Adjacent Cartilage

Objective Hyaluronic acid–transglutaminase (HA-TG) is an enzymatically crosslinkable adhesive hydrogel with chondrogenic properties demonstrated in vitro and in an ectopic mouse model. In this study, we investigated the feasibility of using HA-TG in a collagen scaffold to treat chondral lesions in an ovine model, to evaluate cartilage regeneration in a mechanically and biologically challenging joint environment, and the influence of the surgical procedure on the repair process. Design Chondral defects of 6-mm diameter were created in the stifle joint of skeletally mature sheep. In a 3-month study, 6 defects were treated with HA-TG in a collagen scaffold to test the stability and biocompatibility of the defect filling. In a 6-month study, 6 sheep had 12 defects treated with HA-TG and collagen and 2 sheep had 4 untreated defects. Histologically observed quality of repair tissue and adjacent cartilage was semiquantitatively assessed. Results HA-TG adhered to the native tissue and did not cause any detectable negative reaction in the surrounding tissue. HA-TG in a collagen scaffold supported infiltration and chondrogenic differentiation of mesenchymal cells, which migrated from the subchondral bone through the calcified cartilage layer. Additionally, HA-TG and collagen treatment led to better adjacent cartilage preservation compared with empty defects ( P < 0.05). Conclusions This study demonstrates that the adhesive HA-TG hydrogel in a collagen scaffold shows good biocompatibility, supports in situ cartilage regeneration and preserves the surrounding cartilage. This proof-of-concept study shows the potential of this approach, which should be further considered in the treatment of cartilage lesions using a single-step procedure.

scholarly journals The Potential Use of Platelet-Rich Plasma to Reconstruct the Microtia Chondrocyte in Human Auricular Cartilage Regeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Wei-Hong Chen ◽  
Hen-Yu Liu ◽  
Ching-Yu Tsai ◽  
Chia-che Wu ◽  
Hong-Jian Wei ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Collagen Scaffold ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Surgical Reconstruction ◽  
Auricular Cartilage ◽  
3 Dimensional ◽  
Potential Use ◽  
Specific Mrna

Microtia is characterized as an incomplete auricular development and surgical reconstruction for microtia is still limited even with emerging developments. This study aimed to apply bionanomaterials (PRP/collagen scaffold) for human auricular neocartilage reconstruction by using microtia chondrocytes. The results showed that PRP (TGF-β1 750 pg/mL and 1 ng/mL) increased cell viability of microtia chondrocytes during in vitro 9-day cultures. Additionally, chondrogenic-specific mRNA of Aggrecan and type II collagen (Col II) was significantly and continuously expressed with PRP treatment during the 21-day in vitro expansion. Tissue engineering of auricular neocartilage was performed by seeding microtia chondrocytes in bionanomaterials (PRP/collagen scaffold) 3-dimensional (3D) cultures. Immunohistochemistry (IHC) of Col II showed intensive signals between cells and matrix after 4-week cultures. Conclusion. Our results demonstrated that PRP promotes proliferation and redifferentiation of microtia chondrocytes and provides regenerative potentials in auricular neocartilage reconstruction.

scholarly journals A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells

2021 ◽  
Author(s):  
Rashmi Kumari ◽  
Vasumathy R ◽  
Dhanya Sunil ◽  
Raghumani Singh Ningthoujam ◽  
Badri Narain Pandey ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Tumor Hypoxia ◽  
Binding Pocket ◽  
Docking Studies ◽  
Single Step ◽  
Naphthalic Anhydride ◽  
Hypoxic Conditions ◽  
Fluorescence Measurements ◽  
Enzymatic Reduction

AbstractThe bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4−(6−nitro−1,3−dioxo−1H−benzo[de]isoquinolin−2(3H)−yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4−nitro−1,8−naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR−aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF−7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions. Graphical abstract

scholarly journals Direct antivirals working against the novel coronavirus: azithromycin (DAWn-AZITHRO), a randomized, multicenter, open-label, adaptive, proof-of-concept clinical trial of new antivirals working against SARS-CoV-2—azithromycin trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Iwein Gyselinck ◽  
◽  
Laurens Liesenborghs ◽  
Ewout Landeloos ◽  
Ann Belmans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Cytokine Signaling ◽  
Nasopharyngeal Swab ◽  
The Novel ◽  
Proof Of Concept ◽  
Open Label ◽  
Novel Coronavirus

Abstract Background The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. Methods DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. Discussion The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. Trial registration EU Clinical trials register EudraCT Nb 2020-001614-38. Registered on 22 April 2020

scholarly journals Cell Source-Dependent In Vitro Chondrogenic Differentiation Potential of Mesenchymal Stem Cell Established from Bone Marrow and Synovial Fluid of Camelus dromedarius

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1918
Author(s):  
Young-Bum Son ◽  
Yeon Ik Jeong ◽  
Yeon Woo Jeong ◽  
Mohammad Shamim Hossein ◽  
Per Olof Olsson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Synovial Fluid ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Chondrocyte Differentiation ◽  
Differentiation Potential ◽  
Proliferation Capacity

Mesenchymal stem cells (MSCs) are promising multipotent cells with applications for cartilage tissue regeneration in stem cell-based therapies. In cartilage regeneration, both bone marrow (BM-MSCs) and synovial fluid (SF-MSCs) are valuable sources. However, the cellular characteristics and chondrocyte differentiation potential were not reported in either of the camel stem cells. The in vitro chondrocyte differentiation competence of MSCs, from (BM and SF) sources of the same Camelus dromedaries (camel) donor, was determined. Both MSCs were evaluated on pluripotent markers and proliferation capacity. After passage three, both MSCs showed fibroblast-like morphology. The proliferation capacity was significantly increased in SF-MSCs compared to BM-MSCs. Furthermore, SF-MSCs showed an enhanced expression of transcription factors than BM-MSCs. SF-MSCs exhibited lower differentiation potential toward adipocytes than BM-MSCs. However, the osteoblast differentiation potential was similar in MSCs from both sources. Chondrogenic pellets obtained from SF-MSCs revealed higher levels of chondrocyte-specific markers than those from BM-MSCs. Additionally, glycosaminoglycan (GAG) content was elevated in SF-MSCs related to BM-MSCs. This is, to our knowledge, the first study to establish BM-MSCs and SF-MSCs from the same donor and to demonstrate in vitro differentiation potential into chondrocytes in camels.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

Hypertonic Dextrose Stimulates Chondrogenic Cells to Deposit Collagen and Proliferate

Cartilage ◽  
2021 ◽  
pp. 194760352110145
Author(s):  
Elisha Johnston ◽  
Yi Kou ◽  
Jason Junge ◽  
Lin Chen ◽  
Andrew Kochan ◽  
...  
Keyword(s):  
Metabolic Activity ◽  
Polynomial Regression ◽  
Second Harmonic ◽  
In Vitro Study ◽  
Cartilage Regeneration ◽  
Collagen Deposition ◽  
Cellular Processes ◽  
Photon Excitation ◽  
Hypertonic Dextrose

Objective Hypertonic dextrose (HD) injections (prolotherapy) for osteoarthritis are reported to reduce pain. Cartilage regeneration is hypothesized as a mechanism. This in vitro study identifies an HD concentration that stimulates chondrogenic cells to increase metabolic activity and assesses whether this concentration affects collagen deposition and proliferation. Design ATDC5 chondrogenic cells were cultured in normoglycemic DMEM/F12 medium, treated with concentrations of HD (4-400 mM), and assessed with PrestoBlue. Advanced light microscopy was used to conduct live imaging of collagen deposition through second harmonic generation microscopy (SHG) and proliferation via 2-photon excitation microscopy. Proliferation was additionally assessed with hemocytometer counts. Results A linear regression model found that, relative to the 4 mM baseline control, cells treated with 200 mM had a higher mean absorbance ( P = 0.023) and cells treated with 250 mM were trending toward a higher mean absorbance ( P = 0.076). Polynomial regression interpolated 240 mM as producing the highest average absorbance. Hemocytometer counts validated 250 mM as stimulating proliferation compared with the 4 mM control ( P < 0.01). A concentration of 250 mM HD led to an increase in collagen deposition compared with that observed in control ( P < 0.05). This HD concentration also led to increases in proliferation of ATDC5 cells relative to that of control ( P < 0.001). Conclusions A 250 mM HD solution appears to be associated with increased metabolic activity of chondrocytes, increased collagen deposition, and increased chondrocyte proliferation. These results support clinical prolotherapy research suggesting that intra-articular HD joint injections reduce knee pain. Further study of HD and cellular processes is warranted.

scholarly journals An integrated framework for quantifying immune-tumour interactions in a 3D co-culture model

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gheed Al-Hity ◽  
FengWei Yang ◽  
Eduard Campillo-Funollet ◽  
Andrew E. Greenstein ◽  
Hazel Hunt ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
In Vitro Models ◽  
Proof Of Concept ◽  
Culture Model ◽  
Spheroid Growth ◽  
Confocal Images ◽  
Cancer Spheroids

AbstractInvestigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

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