Publications by authors named "M van Griensven"

292 Publications

The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?

Eur J Med Res 2021 Jun 14;26(1):56. Epub 2021 Jun 14.

Institute for Clinical and Experimental Trauma-Immunology (ITI), University Hospital Ulm, Helmholzstr. 8/1, Ulm, Germany.

Orthopaedic and trauma research is a gateway to better health and mobility, reflecting the ever-increasing and complex burden of musculoskeletal diseases and injuries in Germany, Europe and worldwide. Basic science in orthopaedics and traumatology addresses the complete organism down to the molecule among an entire life of musculoskeletal mobility. Reflecting the complex and intertwined underlying mechanisms, cooperative research in this field has discovered important mechanisms on the molecular, cellular and organ levels, which subsequently led to innovative diagnostic and therapeutic strategies that reduced individual suffering as well as the burden on the society. However, research efforts are considerably threatened by economical pressures on clinicians and scientists, growing obstacles for urgently needed translational animal research, and insufficient funding. Although sophisticated science is feasible and realized in ever more individual research groups, a main goal of the multidisciplinary members of the Basic Science Section of the German Society for Orthopaedics and Trauma Surgery is to generate overarching structures and networks to answer to the growing clinical needs. The future of basic science in orthopaedics and traumatology can only be managed by an even more intensified exchange between basic scientists and clinicians while fuelling enthusiasm of talented junior scientists and clinicians. Prioritized future projects will master a broad range of opportunities from artificial intelligence, gene- and nano-technologies to large-scale, multi-centre clinical studies. Like Prometheus in the ancient Greek myth, transferring the elucidating knowledge from basic science to the real (clinical) world will reduce the individual suffering from orthopaedic diseases and trauma as well as their socio-economic impact.
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http://dx.doi.org/10.1186/s40001-021-00521-xDOI Listing
June 2021

Win, Lose, or Tie: Mathematical Modeling of Ligand Competition at the Cell-Extracellular Matrix Interface.

Front Bioeng Biotechnol 2021 29;9:657244. Epub 2021 Apr 29.

Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.

Integrin transmembrane proteins conduct mechanotransduction at the cell-extracellular matrix (ECM) interface. This process is central to cellular homeostasis and therefore is particularly important when designing instructive biomaterials and organoid culture systems. Previous studies suggest that fine-tuning the ECM composition and mechanical properties can improve organoid development. Toward the bigger goal of fully functional organoid development, we hypothesize that resolving the dynamics of ECM-integrin interactions will be highly instructive. To this end, we developed a mathematical model that enabled us to simulate three main interactions, namely integrin activation, ligand binding, and integrin clustering. Different from previously published computational models, we account for the binding of more than one type of ligand to the integrin. This competition between ligands defines the fate of the system. We have demonstrated that an increase in the initial concentration of ligands does not ensure an increase in the steady state concentration of ligand-bound integrins. The ligand with higher binding rate occupies more integrins at the steady state than does the competing ligand. With cell type specific, quantitative input on integrin-ligand binding rates, this model can be used to develop instructive cell culture systems.
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http://dx.doi.org/10.3389/fbioe.2021.657244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117103PMC
April 2021

Gene therapy for bone healing: lessons learned and new approaches.

Transl Res 2021 May 5. Epub 2021 May 5.

Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota; Musculoskeletal Gene Therapy Research Laboratory, Mayo Clinic, Rochester, Minnesota; IBE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.

Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use. Despite their promising osteogenic properties, the clinical usefulness of recombinant BMPs is hindered by delivery problems that necessitate their application in vastly supraphysiological amounts. This generates adverse side effects, some of them severe, and raises costs; moreover, the clinical efficacy of the recombinant proteins is modest. Gene delivery offers a potential strategy for overcoming these limitations. Our research has focused on delivering a cDNA encoding human BMP-2, because the recombinant protein is Food and Drug Administration approved and there is a large body of data on its effects in people with broken bones. However, there is also a sizeable literature describing experimental results obtained with other transgenes that may directly or indirectly promote bone formation. Data from experiments in small animal models confirm that intralesional delivery of BMP-2 cDNA is able to heal defects efficiently and safely while generating transient, local BMP-2 concentrations 2-3 log orders less than those needed by recombinant BMP-2. The next challenge is to translate this information into a clinically expedient technology for bone healing. Our present research focuses on the use of genetically modified, allografted cells and chemically modified messenger RNA.
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http://dx.doi.org/10.1016/j.trsl.2021.04.009DOI Listing
May 2021

The potential of adipokines in identifying multiple trauma patients at risk of developing multiple organ dysfunction syndrome.

Eur J Med Res 2021 Apr 30;26(1):38. Epub 2021 Apr 30.

Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.

Background: Multiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS.

Methods: In total, 14 multiple trauma patients with an injury severity score (ISS) ≥ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72 h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA.

Results: In the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF.

Conclusions: Leptin and IL-17A could be suitable diagnostic markers to identify severely injured patients with a developing SIRS and MOF earlier, to adjust surgical therapy planning and intensive care.
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http://dx.doi.org/10.1186/s40001-021-00511-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086117PMC
April 2021

Wound fluid under occlusive dressings from diabetic patients show an increased angiogenic response and fibroblast migration.

J Tissue Viability 2021 Mar 5. Epub 2021 Mar 5.

Department for Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technical University of Munich, Germany.

Introduction: Metabolic diseases like diabetes mellitus often show prolonged healing and chronic wounds. Occlusive wound dressings are known to support wound closure by creating a moist environment which supports collagen synthesis, epithelialization and angiogenesis. We aimed to assess the effect of occlusion on diabetic wound fluid on the cellular level regarding fibroblast activity and angiogenetic response.

Material And Methods: 22 split skin donor sites from 22 patients (11 patients with diabetes mellitus) were treated with occlusive dressings intraoperatively. On day 3, fluid and blood serum samples were harvested while changing the dressings. The influence of wound fluid on fibroblasts was assessed by measuring metabolic activity (Alamar Blue assay, Casey Counter), cell stress/death (LDH assay) and migration (in vitro wound healing assay) of fibroblasts. Angiogenesis of endothelial cells (HUVEC) was analyzed with the tube formation assay. Furthermore, a Magnetic Luminex Assay for multi-cytokines detection was performed focusing on inflammatory and pro-angiogenetic cytokines.

Results: The influence of wound fluid under occlusive dressings from diabetic patients showed a significantly increased angiogenic response and fibroblast migration compared to the non-diabetic patient group. Additionally, cell stress was increased in the diabetic group. Cytokine analysis showed an increase in VEGF-A in the diabetic group.

Conclusion: Occlusive dressings may stimulate regenerative effects in diabetic wounds. Our in-vitro study shows the influence of wound fluid under occlusive dressings from diabetic patients on angiogenesis, migration and proliferation of fibroblasts, which are essential modulators of wound healing and scar modulation.
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http://dx.doi.org/10.1016/j.jtv.2021.02.013DOI Listing
March 2021