Skip to main content

Atanas Todorov

University of Basel, Departement of Biomedicine, Adjunct

Universitätsspital Zürich, Cardiac Imaging, Post-Doc

Followers

117

Following

44

Co-authors

12

Public Views

Physician Scientist with dual background in musculoskeletal/general surgery and basic research, focusing on regenerative medicine, tissue engineering and data science. Particular expertise in tendon, cartilage and bone biology and regeneration. Experience in all phases of translation from bench to bedside.

less

Harvard University

Université de Genève

Monica Calabritto

Hunter College

University of Melbourne

Kansas State University

Dr. Goutam Thakur

Manipal Academy of Higher Education

University of Cologne

Johns Hopkins University

Akhilesh Gaharwar

Texas A&M University

Pennsylvania State University

InterestsView All (26)

Uploads

Papers by Atanas Todorov

Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor for critically ill patients needing platelet transfusion—a protocol for the will-plate randomised controlled trial

Trials, Jan 20, 2023

Introduction von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surf... more Introduction von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of the timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on the need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that adding balanced vWF to platelets will reduce the overall need for transfusion of blood products compared to the transfusion of platelets alone. Methods and analysis The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include the number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 h after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and 1-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment.

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

Proceedings of the National Academy of Sciences of the United States of America, Nov 24, 2014

The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has ... more The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developmental processes. The paradigm was exemplified in the context of the skeletal system by testing the osteoinductive capacity of engineered and devitalized hypertrophic cartilage, which is the primordial template for the development of most bones. ECM was engineered by inducing chondrogenesis of human mesenchymal stromal cells and devitalized by the implementation of a death-inducible genetic device, leading to cell apoptosis on activation and matrix protein preservation. The resulting hypertrophic cartilage ECM, tested in a stringent ectopic implantation model, efficiently remodeled to form de novo bone tissue of host origin, including mature vasculature and a hematopoietic compartment. Importantly, cartilage ECM could not generate frank bone tissue if devitalized by standard "freeze & thaw" (F&T) cycles, associated with a significant loss of glycosaminoglycans, mineral content, and ECM-bound cytokines critically involved in inflammatory, vascularization, and remodeling processes. These results support the utility of engineered ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.

Endochondral ossification - towards a clinical translation

not sufficient to improve bone formation of living or devitalized hypertrophic cartilage. While c... more not sufficient to improve bone formation of living or devitalized hypertrophic cartilage. While common precursor monocytes could be attracted by devitalized matrix, their survival and differentiation into osteoclasts depended on interactions with hypertrophic chondrocytes. Presence of M2 macrophages was correlated with subsequent vascularization. Our model is consistent in vitro and in vivo and improves the understanding of end-stage endochondral ossification.

Omnichannel Communication to Boost Patient Engagement and Behavioral Change With Digital Health Interventions

Journal of Medical Internet Research

Digital health interventions are being increasingly incorporated into health care workflows to im... more Digital health interventions are being increasingly incorporated into health care workflows to improve the efficiency of patient care. In turn, sustained patient engagement with digital health interventions can maximize their benefits toward health care outcomes. In this viewpoint, we outline a dynamic patient engagement by using various communication channels and the potential use of omnichannel engagement to integrate these channels. We conceptualize a novel patient care journey where multiple web-based and offline communication channels are integrated through a “digital twin.” The principles of implementing omnichannel engagement for digital health interventions and digital twins are also broadly covered. Omnichannel engagement in digital health interventions implies a flexibility for personalization, which can enhance and sustain patient engagement with digital health interventions, and ultimately, patient quality of care and outcomes. We believe that the novel concept of omnich...

Engineering a functional hematopoietic microenvironment with human MSCs through endochondral ossification

European Cells & Materials, 2013

Atrial fibrillation is associated with poor clinical trajectory of COVID-19

European Heart Journal, 2021

Background Atrial fibrillation (AF) has been described as a common cardiovascular manifestation i... more Background Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and is discussed to be a potential risk factor for a poor clinical course. AF is also already known to be associated with increased risk for all cause death. Purpose In the present study we sought to investigate the impact of AF on the clinical trajectory of patients suffering from COVID-19. Methods We included all patients hospitalized due to COVID-19 in 2020 in our Hospital. A poor clinical trajectory was defined as transfer to intensive care unit (ICU), intermediate care unit (IMC) or death from any cause. Initial ECGs were analyzed in consensus by two experienced readers. First, we compared patients with poor clinical trajectory vs. good clinical course. Secondly, the study population was categorized into two groups with or without AF on admission. A subgroup analysis was performed to differentiate between new onset AF and...

Plastic and Reconstructive Surgery, 2015

Plastic and Reconstructive Surgery, 2014

Short-term delivery of fibrin-bound VEGF protein in osteogenic grafts: increased vascularization with efficient bone formation

The major challenge for biomaterials in bone regeneration is a good integration with the host tis... more The major challenge for biomaterials in bone regeneration is a good integration with the host tissue, in which a proper vasculatization is crucial. Calcium phosphate (CP) materials have gain importance in bone regeneration since it has been proved that they stimulate the formation of bone. However, little is known about their angiogenic potential. Recent findings in our group suggest that Ca 2+ have a role in angiogenesis 1,2,3. In this study we developed different Ca 2+ releasing scaffolds by combining different sol-gel CP degradable nanoparticles (containing only Ca and P) with electrospun polylactic acid (PLA) nanofibers. Scaffolds were seeded with human mesenchymal stem cells (hMSCs) and cultured in both regular (RM) and osteogenic (OM) media. Cell proliferation, Alkaline Phosphatase (ALP) activity, VEGF synthesis and L-lactate release were assessed. Angiogenesis was examined in vitro by HUVEC tube formation and in vivo by using the chick choriallantoic membrane (CAM) angiogenic model. Scaffolds showed a long term (up to 20 days) Ca 2+ release in both culture media. The presence of the particles in the scaffolds enhanced hMSCs adhesion and increased their proliferation as well as the ALP activity in OM. hMSCs substantially increased their production of L-lactate and VEGF when seeded on the scaffolds containing the particles in RM. However, this increase was minimized when cultured in OM. HUVEC showed an enhancement in tube formation when cultured in the conditioned media obtained from culturing the hMSCs on the scaffolds. This time, no differences were found between the scaffolds with or without particles. Finally, the CAM assay showed a significant increase in the formation of new blood vessels for the scaffolds containing the particles. Their angiogenic response was similar to a VEGF loaded PLA fibers used as a positive control. We demonstrate that the presence of the Ca 2+ releasing particles enhanced several angiogenic parameters. However, some of these parameters were significantly reduced in OM due to the osteogenic differentiation of hMSCs.

IL-1β modulates in vitro remodeling and in vivo bone formation by endochondral primed human bone marrow mesenchymal stromal cells

Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19

Journal of Clinical Medicine

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation ... more Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59–80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventil...

Robust coupling of angiogenesis and osteogenesis by VEGF-decorated matrices for bone regeneration

Acta Biomaterialia

Engineering of Functional Endochondral Bone and Haematopoietic Microenvironment with Human Adult Mesenchymal Stromal Cells

Journal of Bone and Joint Surgery-british Volume, 2014

Summary Statement This study reports that hMSC can be manipulated in order to engineer a bone org... more Summary Statement This study reports that hMSC can be manipulated in order to engineer a bone organ, characterised by mature osseous and vascular components and capable to recruit, host and maintain functional HSCs. Introduction Bone tissue engineering strategies are typically based on methods involving adult human Mesenchymal Stromal Cells (hMSC) in a process resembling intramembranous ossification. However, most bones develop and repair through endochondral ossification. In addition, endochondral ossification presents several advantages for regenerative purposes such as osteogenic activity, capability to drive formation of the Hematopoietic Stem Cell (HSC) niche, resistance to hypoxia, intrinsic vasculogenic potential and, consequently, efficiency of engraftment. In this study, we aimed at developing an endochondral bone organ model characterised by functional osseous and hematopoietic compartments by using hMSC. Materials & Methods Expanded hMSC were seeded onto 8 mm diameter, 2 ...

Subchondral bone mesenchymal stromal cells from osteoarthritic lesions give rise to aberrant in vitro and in vivo mineralization

Osteoarthritis and Cartilage, 2016

transcribed into cDNA and changes of expression levels of TGF-beta1-3 were analysed by quantitati... more transcribed into cDNA and changes of expression levels of TGF-beta1-3 were analysed by quantitative Real-Time PCR using sequence-specific primers and probes (TaqMan 5 0-nuclease assays). Results: The WST-1 experiments showed no influence of CoCr particles on the viability of MG63 cells. Cobalt-chloride diminished the MG63 viability only at high concentrations >250 mM.

Omnichannel Communication to Boost Patient Engagement and Behavioural Change with Digital Health Interventions (Preprint)

UNSTRUCTURED Digital health interventions (DHIs) are being increasingly incorporated into healthc... more UNSTRUCTURED Digital health interventions (DHIs) are being increasingly incorporated into healthcare workflows to improve the efficiency of patient care. In turn, sustained patient engagement with DHIs can maximise their benefits towards healthcare outcomes. In this viewpoint, we outline a framework for dynamic patient engagement using various communication channels and the potential use of omnichannel engagement (OCE) to integrate these channels. We conceptualise a novel patient care journey where multiple online and offline communication channels are integrated through a ‘digital twin’. The principles of implementing OCE for DHI and digital twins are also broadly covered. OCE in DHI implies a flexibility for personalisation which can enhance and sustain patient engagement with DHI, and ultimately patient quality of care and outcomes. We believe the novel concept of OCE in healthcare can be greatly beneficial to the patients and the system once it is successfully realised to its fu...

Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury

Scientific Reports, 2021

Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE... more Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia–reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and ...

Abstract 10.55 PLATELET-RICH PLASMA VS. FETAL BOVINE SERUM IN ENGINEERING OF AXIALLY-VASCULARIZED OSTEOGENIC GRAFTS FROM HUMAN ADIPOSE-DERIVED CELLS TO TREAT AVASCULAR NECROSIS OF BONE

Plastic and Reconstructive Surgery - Global Open, 2018

Autologous tissue, like skin grafts and flaps, remain the gold standard for wound coverage. Howev... more Autologous tissue, like skin grafts and flaps, remain the gold standard for wound coverage. However, when autologous tissue isn't practical, whether because of wound size, location, patient's medical status or other factors, then bioengineering skin can provide an alternative to wound coverage while also minimizing patient risk.

Gewebegeneration für den Bewegungsapparat

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum, 2013

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid–Supplemented Tumescent Solution

Annals of Plastic Surgery, 2019

Introduction: In reconstructive surgery, fat volume augmentation is often necessary for esthetic ... more Introduction: In reconstructive surgery, fat volume augmentation is often necessary for esthetic or functional reasons. As an alternative to synthetic and xenogeneic materials, autologous fat grafting (AFG) based on liposuction is gaining popularity, yet successful transplantation and long-term volume maintenance are difficult. Standard tumescent solution formulations neglect adipocyte and stromal vascular fraction (SVF) cell survival during extraction, as well as SVF differentiation into adipocytes thereafter, all of which are crucial for the success of AFG. Here we hypothesized that addition of ascorbic acid (AA) to the tumescent solution could prevent liposuction-induced cell damage. Materials and Methods: The effect of 0.1 mmol/L AA in tumescent solution was investigated in a previously described ex vivo model of AFG. Briefly, excision fat was infiltrated with tumescent solution, with or without AA, and incubated for 20 minutes at 37°C. Hand-assisted liposuction was then performed with a blunt cannula. Total cell viability, clonogenicity, and differentiation capacity of the SVF cells were assessed. Results: With AA, 10.3% more cells and in particular 14.9% more adipocytes survived liposuction. Clonogenicity, adipocyte and osteoblast differentiation by SVF cells remained unchanged. Conclusions: Addition of AA successfully improved survival of adipocytes during liposuction without affecting SVF growth and differentiation. This study therefore identified a useful supplement to the tumescent solution which may lead to improving AFG success.

Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

European Cells and Materials, 2018

Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor for critically ill patients needing platelet transfusion—a protocol for the will-plate randomised controlled trial

Trials, Jan 20, 2023

Introduction von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surf... more Introduction von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of the timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on the need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that adding balanced vWF to platelets will reduce the overall need for transfusion of blood products compared to the transfusion of platelets alone. Methods and analysis The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include the number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 h after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and 1-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment.

Osteoinductivity of engineered cartilaginous templates devitalized by inducible apoptosis

Proceedings of the National Academy of Sciences of the United States of America, Nov 24, 2014

The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has ... more The role of cell-free extracellular matrix (ECM) in triggering tissue and organ regeneration has gained increased recognition, yet current approaches are predominantly based on the use of ECM from fully developed native tissues at nonhomologous sites. We describe a strategy to generate customized ECM, designed to activate endogenous regenerative programs by recapitulating tissue-specific developmental processes. The paradigm was exemplified in the context of the skeletal system by testing the osteoinductive capacity of engineered and devitalized hypertrophic cartilage, which is the primordial template for the development of most bones. ECM was engineered by inducing chondrogenesis of human mesenchymal stromal cells and devitalized by the implementation of a death-inducible genetic device, leading to cell apoptosis on activation and matrix protein preservation. The resulting hypertrophic cartilage ECM, tested in a stringent ectopic implantation model, efficiently remodeled to form de novo bone tissue of host origin, including mature vasculature and a hematopoietic compartment. Importantly, cartilage ECM could not generate frank bone tissue if devitalized by standard "freeze & thaw" (F&T) cycles, associated with a significant loss of glycosaminoglycans, mineral content, and ECM-bound cytokines critically involved in inflammatory, vascularization, and remodeling processes. These results support the utility of engineered ECMbased devices as off-the-shelf regenerative niches capable of recruiting and instructing resident cells toward the formation of a specific tissue.

Endochondral ossification - towards a clinical translation

not sufficient to improve bone formation of living or devitalized hypertrophic cartilage. While c... more not sufficient to improve bone formation of living or devitalized hypertrophic cartilage. While common precursor monocytes could be attracted by devitalized matrix, their survival and differentiation into osteoclasts depended on interactions with hypertrophic chondrocytes. Presence of M2 macrophages was correlated with subsequent vascularization. Our model is consistent in vitro and in vivo and improves the understanding of end-stage endochondral ossification.

Omnichannel Communication to Boost Patient Engagement and Behavioral Change With Digital Health Interventions

Journal of Medical Internet Research

Digital health interventions are being increasingly incorporated into health care workflows to im... more Digital health interventions are being increasingly incorporated into health care workflows to improve the efficiency of patient care. In turn, sustained patient engagement with digital health interventions can maximize their benefits toward health care outcomes. In this viewpoint, we outline a dynamic patient engagement by using various communication channels and the potential use of omnichannel engagement to integrate these channels. We conceptualize a novel patient care journey where multiple web-based and offline communication channels are integrated through a “digital twin.” The principles of implementing omnichannel engagement for digital health interventions and digital twins are also broadly covered. Omnichannel engagement in digital health interventions implies a flexibility for personalization, which can enhance and sustain patient engagement with digital health interventions, and ultimately, patient quality of care and outcomes. We believe that the novel concept of omnich...

Engineering a functional hematopoietic microenvironment with human MSCs through endochondral ossification

European Cells & Materials, 2013

Atrial fibrillation is associated with poor clinical trajectory of COVID-19

European Heart Journal, 2021

Background Atrial fibrillation (AF) has been described as a common cardiovascular manifestation i... more Background Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and is discussed to be a potential risk factor for a poor clinical course. AF is also already known to be associated with increased risk for all cause death. Purpose In the present study we sought to investigate the impact of AF on the clinical trajectory of patients suffering from COVID-19. Methods We included all patients hospitalized due to COVID-19 in 2020 in our Hospital. A poor clinical trajectory was defined as transfer to intensive care unit (ICU), intermediate care unit (IMC) or death from any cause. Initial ECGs were analyzed in consensus by two experienced readers. First, we compared patients with poor clinical trajectory vs. good clinical course. Secondly, the study population was categorized into two groups with or without AF on admission. A subgroup analysis was performed to differentiate between new onset AF and...

Plastic and Reconstructive Surgery, 2015

Plastic and Reconstructive Surgery, 2014

Short-term delivery of fibrin-bound VEGF protein in osteogenic grafts: increased vascularization with efficient bone formation

The major challenge for biomaterials in bone regeneration is a good integration with the host tis... more The major challenge for biomaterials in bone regeneration is a good integration with the host tissue, in which a proper vasculatization is crucial. Calcium phosphate (CP) materials have gain importance in bone regeneration since it has been proved that they stimulate the formation of bone. However, little is known about their angiogenic potential. Recent findings in our group suggest that Ca 2+ have a role in angiogenesis 1,2,3. In this study we developed different Ca 2+ releasing scaffolds by combining different sol-gel CP degradable nanoparticles (containing only Ca and P) with electrospun polylactic acid (PLA) nanofibers. Scaffolds were seeded with human mesenchymal stem cells (hMSCs) and cultured in both regular (RM) and osteogenic (OM) media. Cell proliferation, Alkaline Phosphatase (ALP) activity, VEGF synthesis and L-lactate release were assessed. Angiogenesis was examined in vitro by HUVEC tube formation and in vivo by using the chick choriallantoic membrane (CAM) angiogenic model. Scaffolds showed a long term (up to 20 days) Ca 2+ release in both culture media. The presence of the particles in the scaffolds enhanced hMSCs adhesion and increased their proliferation as well as the ALP activity in OM. hMSCs substantially increased their production of L-lactate and VEGF when seeded on the scaffolds containing the particles in RM. However, this increase was minimized when cultured in OM. HUVEC showed an enhancement in tube formation when cultured in the conditioned media obtained from culturing the hMSCs on the scaffolds. This time, no differences were found between the scaffolds with or without particles. Finally, the CAM assay showed a significant increase in the formation of new blood vessels for the scaffolds containing the particles. Their angiogenic response was similar to a VEGF loaded PLA fibers used as a positive control. We demonstrate that the presence of the Ca 2+ releasing particles enhanced several angiogenic parameters. However, some of these parameters were significantly reduced in OM due to the osteogenic differentiation of hMSCs.

IL-1β modulates in vitro remodeling and in vivo bone formation by endochondral primed human bone marrow mesenchymal stromal cells

Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19

Journal of Clinical Medicine

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation ... more Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59–80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventil...

Robust coupling of angiogenesis and osteogenesis by VEGF-decorated matrices for bone regeneration

Acta Biomaterialia

Engineering of Functional Endochondral Bone and Haematopoietic Microenvironment with Human Adult Mesenchymal Stromal Cells

Journal of Bone and Joint Surgery-british Volume, 2014

Summary Statement This study reports that hMSC can be manipulated in order to engineer a bone org... more Summary Statement This study reports that hMSC can be manipulated in order to engineer a bone organ, characterised by mature osseous and vascular components and capable to recruit, host and maintain functional HSCs. Introduction Bone tissue engineering strategies are typically based on methods involving adult human Mesenchymal Stromal Cells (hMSC) in a process resembling intramembranous ossification. However, most bones develop and repair through endochondral ossification. In addition, endochondral ossification presents several advantages for regenerative purposes such as osteogenic activity, capability to drive formation of the Hematopoietic Stem Cell (HSC) niche, resistance to hypoxia, intrinsic vasculogenic potential and, consequently, efficiency of engraftment. In this study, we aimed at developing an endochondral bone organ model characterised by functional osseous and hematopoietic compartments by using hMSC. Materials & Methods Expanded hMSC were seeded onto 8 mm diameter, 2 ...

Subchondral bone mesenchymal stromal cells from osteoarthritic lesions give rise to aberrant in vitro and in vivo mineralization

Osteoarthritis and Cartilage, 2016

transcribed into cDNA and changes of expression levels of TGF-beta1-3 were analysed by quantitati... more transcribed into cDNA and changes of expression levels of TGF-beta1-3 were analysed by quantitative Real-Time PCR using sequence-specific primers and probes (TaqMan 5 0-nuclease assays). Results: The WST-1 experiments showed no influence of CoCr particles on the viability of MG63 cells. Cobalt-chloride diminished the MG63 viability only at high concentrations >250 mM.

Omnichannel Communication to Boost Patient Engagement and Behavioural Change with Digital Health Interventions (Preprint)

UNSTRUCTURED Digital health interventions (DHIs) are being increasingly incorporated into healthc... more UNSTRUCTURED Digital health interventions (DHIs) are being increasingly incorporated into healthcare workflows to improve the efficiency of patient care. In turn, sustained patient engagement with DHIs can maximise their benefits towards healthcare outcomes. In this viewpoint, we outline a framework for dynamic patient engagement using various communication channels and the potential use of omnichannel engagement (OCE) to integrate these channels. We conceptualise a novel patient care journey where multiple online and offline communication channels are integrated through a ‘digital twin’. The principles of implementing OCE for DHI and digital twins are also broadly covered. OCE in DHI implies a flexibility for personalisation which can enhance and sustain patient engagement with DHI, and ultimately patient quality of care and outcomes. We believe the novel concept of OCE in healthcare can be greatly beneficial to the patients and the system once it is successfully realised to its fu...

Immunoreactivity of the SARS-CoV-2 entry proteins ACE-2 and TMPRSS-2 in murine models of hormonal manipulation, ageing, and cardiac injury

Scientific Reports, 2021

Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE... more Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia–reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and ...

Abstract 10.55 PLATELET-RICH PLASMA VS. FETAL BOVINE SERUM IN ENGINEERING OF AXIALLY-VASCULARIZED OSTEOGENIC GRAFTS FROM HUMAN ADIPOSE-DERIVED CELLS TO TREAT AVASCULAR NECROSIS OF BONE

Plastic and Reconstructive Surgery - Global Open, 2018

Autologous tissue, like skin grafts and flaps, remain the gold standard for wound coverage. Howev... more Autologous tissue, like skin grafts and flaps, remain the gold standard for wound coverage. However, when autologous tissue isn't practical, whether because of wound size, location, patient's medical status or other factors, then bioengineering skin can provide an alternative to wound coverage while also minimizing patient risk.

Gewebegeneration für den Bewegungsapparat

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum, 2013

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid–Supplemented Tumescent Solution

Annals of Plastic Surgery, 2019

Introduction: In reconstructive surgery, fat volume augmentation is often necessary for esthetic ... more Introduction: In reconstructive surgery, fat volume augmentation is often necessary for esthetic or functional reasons. As an alternative to synthetic and xenogeneic materials, autologous fat grafting (AFG) based on liposuction is gaining popularity, yet successful transplantation and long-term volume maintenance are difficult. Standard tumescent solution formulations neglect adipocyte and stromal vascular fraction (SVF) cell survival during extraction, as well as SVF differentiation into adipocytes thereafter, all of which are crucial for the success of AFG. Here we hypothesized that addition of ascorbic acid (AA) to the tumescent solution could prevent liposuction-induced cell damage. Materials and Methods: The effect of 0.1 mmol/L AA in tumescent solution was investigated in a previously described ex vivo model of AFG. Briefly, excision fat was infiltrated with tumescent solution, with or without AA, and incubated for 20 minutes at 37°C. Hand-assisted liposuction was then performed with a blunt cannula. Total cell viability, clonogenicity, and differentiation capacity of the SVF cells were assessed. Results: With AA, 10.3% more cells and in particular 14.9% more adipocytes survived liposuction. Clonogenicity, adipocyte and osteoblast differentiation by SVF cells remained unchanged. Conclusions: Addition of AA successfully improved survival of adipocytes during liposuction without affecting SVF growth and differentiation. This study therefore identified a useful supplement to the tumescent solution which may lead to improving AFG success.

Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

European Cells and Materials, 2018

Introduction to bone tissue engineering via endochondral ossification

General introduction taken from my thesis, containing useful references and concepts.

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid–Supplemented Tumescent Solution

Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their ... more Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ 1 ) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge -with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology -followed by tiered injection therapy over 96 h.

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid–Supplemented Tumescent Solution

Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype

$Research paper thumbnail of Wet milling of large quantities of human excision adipose tissue for the isolation of stromal vascular fraction cells$

Wet milling of large quantities of human excision adipose tissue for the isolation of stromal vascular fraction cells

Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model

Low osmolality and shear stress during liposuction impair cell viability in autologous fat grafting

Monocytes Seeded on Engineered Hypertrophic Cartilage Do Not Enhance Endochondral Ossification Capacity

Contrast-Enhanced Microtomographic Characterisation of Vessels in Native Bone and Engineered Vascularised Grafts Using Ink-Gelatin Perfusion and Phosphotungstic Acid

Engineered Extracellular Matrices as Biomaterials of Tunable Composition and Function

Generation of a Bone Organ by Human Adipose‐Derived Stromal Cells Through Endochondral Ossification

Fat-Derived Stromal Vascular Fraction Cells Enhance the Bone-Forming Capacity of Devitalized Engineered Hypertrophic Cartilage Matrix

Tendon Healing with Growth Factors

Effect of BMP-12, TGF-ß1 and autologous conditioned serum (ACS) on growth factor expression in Achilles tendon healing