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Article ; Online: Effect of Platelet-Rich Plasma Dosing for Healing after Arthroscopic Cuff Repair Compared with Surgery Alone: A Systematic Review and Meta-Analysis.

Nunes, Bernardo / Martins, Ricardo / Linhares, Daniela / Azevedo, Luís / Canadas, Raphäel / Gutierres, Manuel

Medicine and science in sports and exercise

2024 Volume 56, Issue 5, Page(s) 796–804

Abstract: Introduction: Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary aim was to evaluate whether the PRP cell concentration has an effect on ... ...

Abstract	Introduction: Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary aim was to evaluate whether the PRP cell concentration has an effect on tendon healing after aRCR compared with surgery alone. The secondary aim was to assess the functional and pain outcomes. Materials and methods: A systematic review was performed with searches in the MEDLINE (PubMed), Scopus, Web of Science, and Cochrane (Central) databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Metanalytic procedures were performed for randomized controlled trials (RCTs), and a subgroup analysis was used for studies with target (approximately 10 6 cells·μL -1 ) or below-target PRP cellular concentrations (app. 5 × 10 5 cells·μL -1 ) regarding the primary outcome of tendon healing. Results: This review included 10 studies (8 RCTs) with 342 patients in the aRCR + PRP group and 344 patients with isolated aRCR. The risk of bias was low to intermediate (6/4, respectively). Meta-analysis of the RCT revealed that the aRCR + high-concentration PRP group had an approximately 3.9-fold higher chance of healing than the non-PRP group (odds ratio, 3.89; 95% confidence interval, 1.78-8.44; P = 0.0007). No significant difference in healing was found between the aRCR + low-concentration PRP and non-PRP groups (odds ratio, 2.21; 95% confidence interval, 0.66-7.45; P = 0.2). The Constant-Murley score and University of California Los Angeles scores were significantly improved in the aRCR + PRP groups with more than 12 months of follow-up, and no significant differences were found consistently for the American Shoulder and Elbow Society and visual analog scale scores. Conclusions: This study highlights that a PRP cell concentration close to the target (10 6 cells·μL -1 ) of patients with aRCR may improve their healing and functional outcomes and that dosing may be potentially useful in therapy.
MeSH term(s)	Humans ; Rotator Cuff Injuries/surgery ; Rotator Cuff/surgery ; Treatment Outcome ; Wound Healing ; Platelet-Rich Plasma ; Arthroscopy/methods
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	603994-7
ISSN	1530-0315 ; 0195-9131 ; 0025-7990
ISSN (online)	1530-0315
ISSN	0195-9131 ; 0025-7990
DOI	10.1249/MSS.0000000000003361
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Article ; Online: An introduction to network analysis for studies of medication use.

Askar, Mohsen / Cañadas, Raphael Nozal / Svendsen, Kristian

Research in social & administrative pharmacy : RSAP

2021 Volume 17, Issue 12, Page(s) 2054–2061

Abstract: Background: Network Analysis (NA) is a method that has been used in various disciplines such as Social sciences and Ecology for decades. So far, NA has not been used extensively in studies of medication use. Only a handful of papers have used NA in Drug ...

Abstract	Background: Network Analysis (NA) is a method that has been used in various disciplines such as Social sciences and Ecology for decades. So far, NA has not been used extensively in studies of medication use. Only a handful of papers have used NA in Drug Prescription Networks (DPN). We provide an introduction to NA terminology alongside a guide to creating and extracting results from the medication networks. Objective: To introduce the readers to NA as a tool to study medication use by demonstrating how to apply different NA measures on 3 generated medication networks. Methods: We used the Norwegian Prescription Database (NorPD) to create a network that describes the co-medication in elderly persons in Norway on January 1, 2013. We used the Norwegian Electronic Prescription Support System (FEST) to create another network of severe drug-drug interactions (DDIs). Lastly, we created a network combining the two networks to show the actual use of drugs with severe DDIs. We used these networks to elucidate how to apply and interpret different network measures in medication networks. Results: Interactive network graphs are made available online, Stata and R syntaxes are provided. Various useful network measures for medication networks were applied such as network topological features, modularity analysis and centrality measures. Edge lists data used to generate the networks are openly available for readers in an open data repository to explore and use. Conclusion: We believe that NA can be a useful tool in medication use studies. We have provided information and hopefully inspiration for other researchers to use NA in their own projects. While network analyses are useful for exploring and discovering structures in medication use studies, it also has limitations. It can be challenging to interpret and it is not suitable for hypothesis testing.
MeSH term(s)	Aged ; Databases, Factual ; Drug Interactions ; Drug Prescriptions ; Electronic Prescribing ; Humans ; Social Networking
Language	English
Publishing date	2021-06-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2192059-X
ISSN	1934-8150 ; 1551-7411
ISSN (online)	1934-8150
ISSN	1551-7411
DOI	10.1016/j.sapharm.2021.06.021
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Article: Dynamic Culture Systems and 3D Interfaces Models for Cancer Drugs Testing.

Fernandes, Diogo C / Canadas, Raphaël F / Reis, Rui L / Oliveira, Joaquim M

Advances in experimental medicine and biology

2020 Volume 1230, Page(s) 137–159

Abstract: The mass use of biological agents for pharmaceutical purposes started with the development and distribution of vaccines, followed by the industrial production of antibiotics. The use of dynamic systems, such as bioreactors, had been already applied in ... ...

Abstract	The mass use of biological agents for pharmaceutical purposes started with the development and distribution of vaccines, followed by the industrial production of antibiotics. The use of dynamic systems, such as bioreactors, had been already applied in the food industry in fermentation processes and started being used for the development of pharmaceutical agents from this point on. In the last decades, the use of bioreactors and microfluidic systems has been expanded in different fields. The emergence of the tissue engineering led to the development of in vitro models cultured in dynamic systems. This is particularly relevant considering the urgent reduction of the total dependence on animal disease models that is undermining the development of novel drugs, using alternatively human-based models to make the drug discovery process more reliable. The failure out coming from animal models has been more prevalent in certain types of cancer, such as glioblastoma multiform and in high-grade metastatic cancers like bone metastasis of breast or prostatic cancer. The difficulty in obtaining novel drugs for these purposes is mostly linked to the barriers around the tumors, which these bioactive molecules have to overcome to become effective. For that reason, the individualized study of each interface is paramount and is only realistic once applying human-based samples (e.g. cells or tissues) in three-dimensions for in vitro modeling under dynamic conditions. In this chapter, the most recent approaches to model these interfaces in 3D systems will be explored, highlighting their major contributions to the field. In this section, these systems' impact on increased knowledge in relevant aspects of cancer aggressiveness as invasive or motile cellular capacity, or even resistance to chemotherapeutic agents will have particular focus. The last section of this chapter will focus on the integration of the tumor interfaces in dynamic systems, particularly its application on high-throughput drug screening. The industrial translation of such platforms will be discussed, as well as the main upcoming challenges and future perspectives.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Bioreactors ; Cell Culture Techniques/methods ; Drug Screening Assays, Antitumor/methods ; Humans ; Microfluidics ; Models, Biological ; Neoplasms/drug therapy ; Neoplasms/pathology ; Tissue Engineering
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-04-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-36588-2_9
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Article: Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model.

Alegrete, Nuno / Sousa, Susana R / Padrão, Tatiana / Carvalho, Ângela / Lucas, Raquel / Canadas, Raphael F / Lavrador, Catarina / Alexandre, Nuno / Gärtner, Fátima / Monteiro, Fernando J / Gutierres, Manuel

Bioengineering (Basel, Switzerland)

2023 Volume 10, Issue 2

Abstract: The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing ...

Abstract	The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.
Language	English
Publishing date	2023-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering10020206
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Article: Bioreactors and Microfluidics for Osteochondral Interface Maturation.

Canadas, Raphaël F / Marques, Alexandra P / Reis, Rui L / Oliveira, J Miguel

Advances in experimental medicine and biology

2018 Volume 1059, Page(s) 395–420

Abstract: The cell culture techniques are in the base of any biology-based science. The standard techniques are commonly static platforms as Petri dishes, tissue culture well plates, T-flasks, or well plates designed for spheroids formation. These systems faced a ... ...

Abstract	The cell culture techniques are in the base of any biology-based science. The standard techniques are commonly static platforms as Petri dishes, tissue culture well plates, T-flasks, or well plates designed for spheroids formation. These systems faced a paradigm change from 2D to 3D over the current decade driven by the tissue engineering (TE) field. However, 3D static culture approaches usually suffer from several issues as poor homogenization of the formed tissues and development of a necrotic center which limits the size of in vitro tissues to hundreds of micrometers. Furthermore, for complex tissues as osteochondral (OC), more than recovering a 3D environment, an interface needs to be replicated. Although 3D cell culture is already the reality adopted by a newborn market, a technological revolution on cell culture devices needs a further step from static to dynamic already considering 3D interfaces with dramatic importance for broad fields such as biomedical, TE, and drug development. In this book chapter, we revised the existing approaches for dynamic 3D cell culture, focusing on bioreactors and microfluidic systems, and the future directions and challenges to be faced were discussed. Basic principles, advantages, and challenges of each technology were described. The reported systems for OC 3D TE were focused herein.
MeSH term(s)	Animals ; Biological Transport ; Bioreactors ; Bone and Bones/cytology ; Cell Communication ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cells, Cultured ; Chondrocytes/cytology ; Chondrogenesis/physiology ; Equipment Design ; Forecasting ; Humans ; Implants, Experimental ; Lab-On-A-Chip Devices ; Microfluidics/methods ; Osteogenesis/physiology ; Rheology ; Tissue Engineering/methods
Language	English
Publishing date	2018-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-76735-2_18
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Article: Bioengineered Nanoparticles Loaded-Hydrogels to Target TNF Alpha in Inflammatory Diseases.

Oliveira, Isabel Matos / Fernandes, Diogo Castro / Maia, Fátima Raquel / Canadas, Raphael Faustino / Reis, Rui Luís / Oliveira, Joaquim Miguel

Pharmaceutics

2021 Volume 13, Issue 8

Abstract: Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patients' mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. ... ...

Abstract	Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patients' mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. The present study offers two novel therapies based in advanced drug delivery systems for RA treatment: encapsulated chondroitin sulfate modified poly(amidoamine) dendrimer nanoparticles (NPs) covalently bonded to monoclonal anti-TNF α antibody in both Tyramine-Gellan Gum and Tyramine-Gellan Gum/Silk Fibroin hydrogels. Using pro-inflammatory THP-1 (i.e., human monocytic cell line), the therapy was tested in an inflammation in vitro model under both static and dynamic conditions. Firstly, we demonstrated effective NP-antibody functionalization and TNF-α capture. Upon encapsulation, the NPs were released steadily over 21 days. Moreover, in static conditions, the approaches presented good anti-inflammatory activity over time, enabling the retainment of a high percentage of TNF α. To mimic the physiological conditions of the human body, the hydrogels were evaluated in a dual-chamber bioreactor. Dynamic in vitro studies showed absent cytotoxicity in THP-1 cells and a significant reduction of TNF-α in suspension over 14 days for both hydrogels. Thus, the developed approach showed potential for use as personalized medicine to obtain better therapeutic outcomes and decreased adverse effects.
Language	English
Publishing date	2021-07-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13081111
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Article ; Online: 3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network.

Canadas, Raphaël F / Costa, João B / Mao, Zhengwei / Gao, Changyou / Demirci, Utkan / Reis, Rui L / Marques, Alexandra P / Oliveira, Joaquim M

Biomaterials

2021 Volume 277, Page(s) 121112

Abstract: Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, ... ...

Abstract	Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.
MeSH term(s)	Coculture Techniques ; Cryogels ; Porosity ; Regenerative Medicine ; Tissue Engineering ; Tissue Scaffolds
Chemical Substances	Cryogels
Language	English
Publishing date	2021-08-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2021.121112
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Article: 3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network

Canadas, Raphaël F. / Costa, João B. / Mao, Zhengwei / Gao, Changyou / Demirci, Utkan / Reis, Rui L. / Marques, Alexandra P. / Oliveira, Joaquim M.

Biomaterials. 2021 Oct., v. 277

2021

Abstract	Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.
Keywords	anisotropy ; biocompatible materials ; biomarkers ; biomechanics ; coculture ; cryogels ; drugs ; extracellular matrix ; ice ; isotropy ; liver cirrhosis ; medicine ; osteopontin
Language	English
Dates of publication	2021-10
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2021.121112
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Numerical and experimental simulation of a dynamic-rotational 3D cell culture for stratified living tissue models.

Canadas, Raphaël F / Liu, Ziyu / Gasperini, Luca / Fernandes, Diogo C / Maia, Fátima R / Reis, Rui L / Marques, Alexandra P / Liu, Chaozong / Oliveira, Joaquim M

Biofabrication

2022 Volume 14, Issue 2

Abstract: Human tissues and organs are inherently heterogeneous, and their functionality is determined by the interplay between different cell types, their secondary architecture, and gradients of signalling molecules and metabolites. To mimic the dynamics of ... ...

Abstract	Human tissues and organs are inherently heterogeneous, and their functionality is determined by the interplay between different cell types, their secondary architecture, and gradients of signalling molecules and metabolites. To mimic the dynamics of native tissues, perfusion bioreactors and microfluidic devices are widely used in tissue engineering (TE) applications for enhancing cell culture viability in the core of 3D constructs. Still, most
MeSH term(s)	Bioreactors ; Cell Culture Techniques, Three Dimensional ; Computer Simulation ; Humans ; Perfusion ; Tissue Engineering/methods
Language	English
Publishing date	2022-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2500944-8
ISSN	1758-5090 ; 1758-5082
ISSN (online)	1758-5090
ISSN	1758-5082
DOI	10.1088/1758-5090/ac55a2
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Article: Ionic Liquid-Mediated Processing of SAIB-Chitin Scaffolds

Gonçalves, Cristiana / Silva, Simone S / Gomes, Joana M / Oliveira, Isabel M / Canadas, Raphaël F / Maia, F. Raquel / Radhouani, Hajer / Reis, Rui L / Oliveira, Joaquim M

ACS sustainable chemistry & engineering. 2020 Feb. 14, v. 8, no. 9

2020

Abstract: This study proposes a green and innovative ionic liquid (IL) methodology for processing sucrose acetate isobutyrate (SAIB) porous structures for tissue engineering. The solubilization of SAIB in an IL, namely, 1-butyl-imidazolium acetate, was achieved, ... ...

Abstract	This study proposes a green and innovative ionic liquid (IL) methodology for processing sucrose acetate isobutyrate (SAIB) porous structures for tissue engineering. The solubilization of SAIB in an IL, namely, 1-butyl-imidazolium acetate, was achieved, for the first time, allowing the development of SAIB-based scaffolds. In the early stages of the process development, it was needed to add chitin in the scaffold’s compositions to provide a steady structure. Physicochemical, mechanical, and biological techniques evaluated the characteristics of the produced scaffolds. The Fourier transform infrared spectroscopy results confirmed the presence of chitin and SAIB, as well as the influence of the applied solvent for the IL removal. The X-ray diffraction analysis shows that the presence of SAIB contributes to a decrease in the crystallinity of the scaffolds. Moreover, the morphology of the structures varied upon the preparation conditions used, demonstrating that it is possible to obtain scaffolds with different values of porosity (ranging from 52 to 85%). No cytotoxicity was found when culturing in vitro human adipose-derived stem cells onto the surface of the produced scaffolds during 72 h. This study showed that processing SAIB-based scaffolds is feasible using ILs and that these structures exhibit promising features for tissue engineering scaffolding applications.
Keywords	Fourier transform infrared spectroscopy ; X-ray diffraction ; acetates ; chitin ; crystal structure ; cytotoxicity ; humans ; ionic liquids ; porosity ; solubilization ; stem cells ; sucrose ; tissue engineering
Language	English
Dates of publication	2020-0214
Size	p. 3986-3994.
Publishing place	American Chemical Society
Document type	Article
ISSN	2168-0485
DOI	10.1021/acssuschemeng.0c00385
Database	NAL-Catalogue (AGRICOLA)

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