Refine
Has Fulltext
- yes (155)
Is part of the Bibliography
- yes (155)
Year of publication
Document Type
- Journal article (107)
- Doctoral Thesis (48)
Keywords
- Tissue Engineering (24)
- tissue engineering (10)
- in vitro (5)
- regenerative medicine (5)
- stem cells (5)
- 3D tissue model (4)
- In-vitro-Kultur (4)
- extracellular matrix (4)
- gene expression (4)
- inflammation (4)
- BMP-2 (3)
- Bordetella pertussis (3)
- In vitro (3)
- Stammzelle (3)
- Zellkultur (3)
- bone regeneration (3)
- chondrocytes (3)
- collagens (3)
- decellularization (3)
- electrospinning (3)
- 3D tumour model (2)
- B cells (2)
- BMP (2)
- Bone morphogenetic protein-2 (2)
- Cancer (2)
- Dünndarm (2)
- Elektrospinnen (2)
- Fibroblasts (2)
- GMP (2)
- Gewebekultur (2)
- Hautmodell (2)
- Hirschsprung disease (2)
- Hyaliner Knorpel (2)
- Immuntherapie (2)
- Implantat (2)
- Kollagen (2)
- Kreuzband (2)
- Ligamentum cruciatum anterius (2)
- Medizinprodukt (2)
- Melanom (2)
- Mundschleimhaut (2)
- Neisseria gonorrhoeae (2)
- Osteoarthritis (2)
- Raman-Spektroskopie (2)
- Regenerative Medizin (2)
- SARS-CoV-2 (2)
- Tumormodell (2)
- Validierung (2)
- Vaskularisation (2)
- Vaskularisierung (2)
- Wundheilung (2)
- anthocyanins (2)
- bioengineering (2)
- biological models (2)
- bioreactor (2)
- blood-brain barrier (BBB) model (2)
- burn wound (2)
- cartilage (2)
- cartilage regeneration (2)
- co-culture (2)
- colorectal cancer (2)
- discriminant analysis (2)
- extracellular vesicles (2)
- growth factor beta (2)
- immunotherapy (2)
- impedance spectroscopy (2)
- infection (2)
- intestinal in vitro model (2)
- invasion (2)
- lung cancer (2)
- mesenchymal stem cells (2)
- multiple myeloma (2)
- osteoarthritis (2)
- pancreas (2)
- permeability (2)
- phenotype (2)
- principal component analysis (2)
- raman spectroscopy (2)
- rat (2)
- reconstructed human epidermis (2)
- scaffolds (2)
- subcutaneous animal model (2)
- targeted therapy (2)
- therapy (2)
- vascularization (2)
- wound healing (2)
- 1st-line treatment (1)
- 3D (1)
- 3D Modell (1)
- 3D Tumormodell (1)
- 3D in vitro Modell (1)
- 3D in vitro model (1)
- 3D in vitro models (1)
- 3D lung tumor tissue models (1)
- 3D model (1)
- 3D models (1)
- 3D scaffolds (1)
- 3D tissue models (1)
- 3D-Elektrode (1)
- 3D-Kultur (1)
- 5-Fluorouracil (1)
- ACL construct (1)
- ATMP (1)
- Adenocarcinom (1)
- Adenokarzinom (1)
- Adenylate cyclase toxin (1)
- Advanced Therapy Medicinal Products (ATMP) (1)
- Akute myeloische Leukämie (1)
- Alternative test methods (1)
- Alternative zum Tierversuch (1)
- Alzheimer′s disease (1)
- Anastomoseninsuffizienz (1)
- Angiogenese (1)
- Anterior Cruciate Ligament (1)
- Antikörper (1)
- Apoptosis (1)
- Arthroseentstehung (1)
- Articular-Cartilage (1)
- Arzneimittel (1)
- Arzneimittelzulassung (1)
- Assay (1)
- Atemwege (1)
- Atemwegsschleimhaut (1)
- Automation (1)
- B cell receptors (1)
- BMP signaling (1)
- BMP-2 delivery (1)
- BRAF mutation (1)
- BRAF-mutant (1)
- BRAF-mutiert (1)
- BSGC (1)
- Bakterielle Nanocellulose (1)
- Bauchspeicheldrüse (1)
- Beta-catenin (1)
- Bindegewebe (1)
- BioVaSc (1)
- Biocompatibility (1)
- Biodegradable polymer scaffolds (1)
- Biodistribution (1)
- Biokompatibilität (1)
- Biomaterial (1)
- Biomechanical Properties (1)
- Biomedical engineering (1)
- Bioreactor (1)
- Bone morphogenetic protein 2 (1)
- Bone tissue engineering (1)
- Brustkrebs (1)
- CAR T cell (1)
- CCR2 (1)
- CCR4 (1)
- CNS disease (1)
- CYP induction (1)
- CYP inhibition (1)
- CYR61 (1)
- Caco2 cells (1)
- Carcinoma cells (1)
- Cardiac ventricles (1)
- Cell replacement therapy (1)
- Chemicals (1)
- Collagen (1)
- Compressive Properties (1)
- Cytokeratine (1)
- Data acquisition (1)
- Dezellularisierung (1)
- Diabetes mellitus (1)
- Dickdarmtumor (1)
- Diffusion tensor imaging (1)
- Dosis-Wirkungs-Beziehung (1)
- Draize eye test (1)
- Drug testing (1)
- ECM coating (1)
- EMT (1)
- EVs (1)
- Eigenvectors (1)
- Eisenoxid-Nanopartikel (1)
- Electrochemical Impedance Spectroscopy (1)
- Electrode (1)
- Electrospinning (1)
- Elektrode (1)
- Enteric nervous system (1)
- Enteric neuropathies (1)
- Entwicklung (1)
- Epidermis (1)
- Epidermismodell (1)
- Episkin (1)
- Epithel (1)
- Eriodictyon californicum (1)
- Extrazellulärmatrix (1)
- Eye irritation (1)
- FGF signaling (1)
- FTIR spectroscopy (1)
- Fibroblast (1)
- Fibrose (1)
- Fluorouracil (1)
- Fremdkörpermodell (1)
- GDF-5 (1)
- GLP-1 (1)
- GLUTs (1)
- GUT (1)
- Gastrointestinaltrakt (1)
- Gefitinib (1)
- Gelatine (1)
- Gene regulation (1)
- Gewebemodell (1)
- Gewebemodelle (1)
- Glucose transport (1)
- Growth; BMP-2 (1)
- HUVEC (1)
- Halofuginon (1)
- Haut (1)
- Hautverbrennung (1)
- Head and neck cancers (1)
- Heart (1)
- Hemofiltration (1)
- Herzschrittmacher (1)
- Hirschsprung disease liability (1)
- Human Knee (1)
- Human Medial Meniscus (1)
- Humanparasitologie (1)
- Hydrogel (1)
- Hypertrophic pyloric-stenosis (1)
- Hämophilie A (1)
- IL-1ß (1)
- IL-6 (1)
- In vitro skin irritation testing (1)
- In-vitro (1)
- In-vitro-Testsystem (1)
- In-vivo (1)
- Individualisierte Medizin (1)
- Induced pluripotent stem cells (1)
- Induzierte pluripotente Stammzelle (1)
- Infektionsstudien (1)
- Injuries (1)
- Intestinal pseudoobstruction (1)
- Intestinal stem cell (1)
- Invasion (1)
- Irritable bowel syndrome (1)
- Ischämie (1)
- KRAS biomarker signatures (1)
- Kernspintomografie (1)
- Kniegelenk (1)
- Knochenimplantat (1)
- Knochenregeneration (1)
- Knorpelimplantate (1)
- Kohlenstoff (1)
- Kohlenstofffaser (1)
- Krebs <Medizin> (1)
- Kreuzbandersatz (1)
- Kryokonservierung (1)
- Künstliche Ingelligenz (1)
- LCST (1)
- LDH-assay (1)
- Lactatdehydrogenase (1)
- Lgr5 (1)
- Lungenkrebs (1)
- Lungentumor (1)
- MRT (1)
- MSC (1)
- Magen (1)
- Magenchirurgie (1)
- Magenkrankheit (1)
- Magnet-Partikel-Spektroskopie (1)
- Magnetic resonance imaging (1)
- Mamma carcinoma (1)
- Mammakarzinom (1)
- Mandibular continuity defects (1)
- Marketing authorisation of pharmaceuticals (1)
- Marrow stromal cells (1)
- Matrix (1)
- Mechanical deformation (1)
- Mechanisms (1)
- Medicine (1)
- Mesenchymal Stem Cell (1)
- Mesenchymal transition (1)
- Mesenchymale Stammzellen (1)
- Microenvironment (1)
- Mikrowellen (1)
- Minipig (1)
- Model (1)
- Models (1)
- Molekularbiologie (1)
- Monitoring (1)
- Mukosamodell (1)
- Multicenter randomized-trial (1)
- Multilayered skin tissue model (1)
- Mundschleimhautäquivalent (1)
- Myofibroblast differentiation (1)
- NK cells (1)
- NMR (1)
- NOTCH (1)
- NOTES <Chirurgie> (1)
- NRAS mutation (1)
- Nanofaser (1)
- Neisseria meningitidis (1)
- Neuartige Arzneimittel (1)
- Neural crest cells (1)
- Nitric-oxide (1)
- OECD guideline (1)
- OLFM4 (1)
- Onchocerca volvulus (1)
- Onchozerkose (1)
- Open source reconstructed epidermis (1)
- Oral squamous cell carcinoma (1)
- Oralmukosa (1)
- Oralmukosamodell (1)
- Oxide synthase gene (1)
- PLGA (1)
- Paclitaxel (1)
- Pancreatic islet (1)
- Pankreas (1)
- Pankreaskarzinom (1)
- Parasitology (1)
- Partikel (1)
- Perforation <Medizin> (1)
- Perfusion Bioreactor (1)
- Plattenepithelcarcinom (1)
- Pleuramesotheliom (1)
- Polylactid-co-Glycolid (1)
- Preclinical studies (1)
- Primär-basierte immortalisierte Zelllinie (1)
- Primäre Ziliendyskinesie (1)
- Proliferation (1)
- Protein chemistry (1)
- Protein-Tyrosin-Kinasen (1)
- Präklinische Studien (1)
- QPCR (1)
- R57A (1)
- RHE (1)
- RT-qPCR (1)
- Rat mynteric plexus (1)
- Real time quantitative PCR (1)
- Receptor (1)
- Repair (1)
- Reperfusion (1)
- Resistenzentwicklung (1)
- Respiratorisches System (1)
- SGLTs (1)
- SIS/MUC (1)
- Salinomycin (1)
- Salmonella (1)
- Salmonella Typhimurium (1)
- Scaffold bone implant (1)
- Sglt1 (1)
- Silikon (1)
- Sinus floor augmentation (1)
- Skin Tissue Engineering (1)
- Slow-transit constipation (1)
- Smooth-muscle-cells (1)
- Squamous-cell carcinoma (1)
- Stammzellforschung (1)
- Stem cells (1)
- Stem-cell biotechnology (1)
- Stimulation (1)
- Stroma (1)
- Swine (1)
- T-Zell-rekrutierende Antikörperkonstrukte (1)
- TEER (1)
- TEER-Wert (1)
- TGF-beta (1)
- TGFβ/BMP signaling (1)
- TNBC (1)
- Targeted therapies (1)
- Term follow-up (1)
- Test system (1)
- Therapeutisches System (1)
- Therapie (1)
- Therapiesimulation (1)
- Tipifarnib (1)
- Tissue (1)
- Tractography (1)
- Triple co-culture (1)
- Tumor models (1)
- Tumorigenicity (1)
- Tumormikroumgebung (1)
- Tumorzelllinien (1)
- Validation (1)
- Vascularized (1)
- Viabilität (1)
- Vivo (1)
- Vorderes Kreuzband (1)
- Wirkstofftestung (1)
- Zell-Migration (1)
- Zelldifferenzierung (1)
- Zellkulturmodell (1)
- acetylsalicylic acid (1)
- acid dissociation (1)
- acute myeloid leukemia (1)
- adenocarcinoma of the lung (1)
- adenylate cyclase toxin (1)
- adhesion (1)
- adults (1)
- aging (1)
- air-liquid interface (1)
- airway epithelia (1)
- airways (1)
- albumins (1)
- algorithm (1)
- alternative to animal testing (1)
- alternatives (1)
- anaesthetics (1)
- anatomy (1)
- animal model (1)
- antagonist (1)
- antennas (1)
- anthocyanin (1)
- antibiotics (1)
- antioxidative (1)
- antitumor peptide (1)
- antiviral activity (1)
- apoptosis (1)
- artificial membrane-permeability (1)
- aspirin (1)
- astaxanthin (1)
- asthmatic bronchial epithelium (1)
- astrocytes (1)
- autologous (1)
- autologous chondrocyte implantation (1)
- automation (1)
- automation & robotics (1)
- bacteria (1)
- bacterial cellulose dressing (1)
- bacterial migration (1)
- bacterial nanocellulose (1)
- bacterial virulence (1)
- barrier models (1)
- benzalkonium chloride (1)
- beta cell (1)
- beta-aminopropionitrile (1)
- beta-cyclodextrin (1)
- betaglycan (1)
- bilberry (1)
- biocompatibility (1)
- biocompatible materials (1)
- bioconjugation (1)
- biofilm (1)
- bioinformatics (1)
- biological barriers (1)
- biological scaffold (1)
- biological scaffolds (1)
- biology (1)
- biomaterial tests (1)
- biomedical engineering (1)
- biomedical materials (1)
- biomimetic 3D tissue model (1)
- bioreactor culture (1)
- biotechnology (1)
- black currant (1)
- blood (1)
- blood glucose regulation (1)
- blood pressure (1)
- blood-brain barrier (1)
- blood-cerebrospinal fluid barrier (1)
- blood‐brain barrier (BBB) (1)
- bone (1)
- bone critical size defect (1)
- bone marrow (1)
- bone morphogenetic protein (1)
- bone morphogenetic protein 2 (BMP2) (1)
- bone morphogenetic protein 9 (BMP9) (1)
- bone morphogenetic proteins (1)
- boolean in silico models (1)
- brachtydacyly type A2 (1)
- brain endothelial cells (1)
- brain–liver chip (1)
- breast cancer cells (1)
- calcium fluoride nanoparticles (1)
- cancer dissemination (1)
- cancer treatment (1)
- cancers and neoplasms (1)
- carbon fiber (1)
- cardiac device therapy (1)
- cardiac patch (1)
- cardiac tissue (1)
- cardiovascular (1)
- cardiovascular MR methods (1)
- cartilage defectex vivo model (1)
- cartilage repair (1)
- cartilage test system (1)
- cell binding (1)
- cell culture (1)
- cell cultures (1)
- cell cycle and cell division (1)
- cell differentiation (1)
- cell engineering (1)
- cell membrane model (1)
- cell metabolism (1)
- cell migration (1)
- cell proliferation (1)
- cellular biology (1)
- cellular microenvironment (1)
- cellular signalling networks (1)
- central nervous system (1)
- ceramide (1)
- chemokine receptor (1)
- chiral resolution (1)
- chondrogenesis (1)
- chondrogenic differentiation (1)
- chondrogenic hypertrophy (1)
- ciliary neurotrophic factor (1)
- ciliostasis (1)
- circular dichroism (1)
- clinical applications (1)
- collagen sponge (1)
- collagen type I hydrogel (1)
- colllagen (1)
- colon (1)
- colony-stimulating factor (1)
- combination of physical vapor deposition and electrochemical etching (1)
- combinatorial drug predictions (1)
- complexation (1)
- computer modelling (1)
- confocal Raman imaging (1)
- core depression (1)
- coreceptor (1)
- corneal endothelium (1)
- corneal epithelium (1)
- corneal equivalent (1)
- corneal storage (1)
- covalent coupling (1)
- critical size defect (1)
- cross-talk (1)
- cryokonservation (1)
- cryostructured scaffolds (1)
- crystal structure (1)
- crystal-structure (1)
- culture techniques (1)
- cultured (1)
- cyclic adenosine monophosphate (1)
- cycloaddition (1)
- cyclodextrin (1)
- cytokine (1)
- cytokines (1)
- cytotoxicity (1)
- defects (1)
- defined humanized test system (1)
- dendritic cell (1)
- development (1)
- diabetes (1)
- differentiation (1)
- diffusion tensor imaging (1)
- dominant-negative mutatio (1)
- drug (1)
- drug delivery (1)
- drug metabolism (1)
- drug permeability screening (1)
- drug resistance (1)
- dry spinning (1)
- dynamic culture (1)
- dynamic culture conditions (1)
- dystrophic RCS rats (1)
- early diagnosis (1)
- ectopic bone formation (1)
- elastic fibers (1)
- elastin (1)
- electrical and electronic engineering (1)
- electrode scaffold (1)
- embryonic stem cell (1)
- embryonic stem cells (1)
- endothelial cells (1)
- endothelial growth factor (1)
- enteric nervous system (1)
- enzyme metabolism (1)
- epidermis (1)
- epithelial cell culture (1)
- epithelial cells (1)
- equipment and supplies (1)
- establishment (1)
- ex vivo model (1)
- experimental models of disease (1)
- expression (1)
- eye irritation testing (1)
- factor binding profiles (1)
- factor-VIII (1)
- fibroblast chemotaxis (1)
- fibroblast growth factor (1)
- fibrosis (1)
- filamentous Salmonella Typhimurium (1)
- fixation (1)
- flavonoids (1)
- foreign body reaction (1)
- formalin (1)
- fremdkörper assoziierte Reaktion (1)
- full thickness skin (1)
- functional initiators (1)
- gamma-cyclodextrin (1)
- gastrointestinal tract (1)
- gels (1)
- gene encoding noggin (1)
- gene therapy (1)
- genetic engineering (1)
- glucose (1)
- glycoprotein (1)
- growth and differentiation factor 5 (1)
- hBMSC (1)
- head and neck squamous cell carcinoma (1)
- heart structure (1)
- heart valve (1)
- heparin binding sites (1)
- heptaocytes (1)
- herpesvirus (1)
- highly porous materials (1)
- host (1)
- human (1)
- human airway mucosa tissue models (1)
- human bruchs membrane (1)
- human exposure (1)
- human heptocytes (1)
- human induced pluripotent stem cells (hiPSCs) (1)
- human induced pluripotent stem cells (hiPSCs)human induced pluripotent stem cells (hiPSCs) (1)
- human liver cells (1)
- human nasal epithelial cells (1)
- human osteosarcoma xenografts (1)
- human respiratory epithelial cells (1)
- human tracheo-bronchial epithelial cells (1)
- humane mesenchymale Stammzellen (1)
- human‐induced pluripotent stem cells (hiPSC) (1)
- hyaline cartilage (1)
- hybrid pacemaker (1)
- hyperlipidemia (1)
- hypoxia inducible factor 1 (1)
- immune cell infiltration (1)
- immunotherapeutics (1)
- immunotherapies (1)
- implant (1)
- in silico simulation (1)
- in situ guided tissue regeneration (1)
- in vitro Modelle (1)
- in vitro model (1)
- in vitro models (1)
- in vitro-Testsystem (1)
- in vivo (1)
- in vivo experiments (1)
- in vivo study (1)
- in-vitro (1)
- in-vitro models (1)
- in-vitro-Modell (1)
- in-vitro-Testsysteme (1)
- induced pluripotent stem cells (1)
- induction (1)
- infectious disease (1)
- inflammation-induced tissue demage (1)
- inflammatory bowel disease (1)
- inflammatory response (1)
- insulin (1)
- interface (1)
- intestinal enteroids (1)
- intestine (1)
- invasiveness (1)
- invitro (1)
- inflammatory response (1)
- iron metabolism (1)
- irradiation (1)
- islets of Langerhans (1)
- kinetics (1)
- kolorektales Karzinom (1)
- label-free analysis (1)
- laser microdissection (1)
- ligand binding (1)
- ligand-receptor complex (1)
- ligand-receptor promiscuity (1)
- lipids (1)
- liposome (1)
- living cells (1)
- lncRNAs (1)
- long-term (1)
- lower critical solution temperature (1)
- lung and intrathoracic tumors (1)
- magnetic resonance imaging (MRI) (1)
- malignant tumors (1)
- manufacturing (1)
- measels virus (1)
- measles virus (1)
- mechanisms of disease (1)
- medicine (1)
- melanoma metastases (1)
- membrane receptor signaling (1)
- memory (1)
- meningococcus (1)
- mesenchymal cells (1)
- mesenchymal stromal cell (1)
- mesenchymal tissues (1)
- metabolic flux analysis (1)
- metallo-supramolecular polymer (1)
- miRNAs (1)
- microbe carrier (1)
- microenvironment (1)
- microparticles (1)
- microphysiologic 3D tumour model (1)
- microphysiological systems (MPS) (1)
- microplastics (1)
- microvascular endothelial cells (1)
- microwave radiation (1)
- midazolam (1)
- migration (1)
- modular tumor tissue models (1)
- moisture balance (1)
- molecular biology (1)
- molecular diagnostics (1)
- molecular mechanism (1)
- morphogenetic protein receptors (1)
- motility disorders (1)
- multi-organ chip (1)
- multicellular tumor spheroids (1)
- multifunctional nanoparticles (1)
- multilayered skin (1)
- multimodal imaging (1)
- multipotent fetal neural stem cells (fNSCs) (1)
- multivariate data analysis (1)
- murine (1)
- mutagenesis (1)
- myenteric plexus (1)
- nanoparticles (1)
- nanoplastics (1)
- nanotopographical surfaces (1)
- necrosis-factor-alpha (1)
- necrotic cell death (1)
- neural stem-cell (1)
- neurology (1)
- neuronal electrodes (1)
- neurotoxicity (1)
- neurovascular unit in vitro (1)
- neutrophil transmigration (1)
- non-invasive biomarkers (1)
- occupancy (1)
- olfactomedin 4 (1)
- on-a-chip (1)
- open-access database (1)
- open-source epidermis (1)
- oragnoids (1)
- oral mucosa model (1)
- orales Plattenepithelkarzinomäquivalent (1)
- organ-on-a-chip (1)
- organotypic (1)
- osteoblasts (1)
- osteochondral allografts (1)
- osteochondral biopsy (1)
- osteochondral lesion (1)
- osteogenesis imperfecta (1)
- osteogenic differentiation (1)
- osteoporosis (1)
- outgrowth endothelial cells (1)
- ovarian cancer (1)
- oxidative DNA damage (1)
- pancreatic cancer (1)
- pancreatic differentiation (1)
- parasitology (1)
- perfused hydrogel (1)
- perfusion-based bioreactor system (1)
- peritoneal metastasis (1)
- pharmaceutical applications (1)
- phosphatidylserine (1)
- photoluminescence (1)
- physiology (1)
- platelet-derived growth factor (1)
- pluripotent stem cells (1)
- polymer (1)
- polymerization (1)
- polymers (1)
- polypeptoids (1)
- postpolymerization modification (1)
- precision-cut lung slices (1)
- preclinical drug discovery (1)
- primary cell isolation (1)
- primary cells (1)
- primary ciliary dyskinesia (1)
- primary human hepatocytes (1)
- primary-cell-derived immortalized cell line (1)
- progenitor cells (1)
- progenitors (1)
- protein immobilization (1)
- proteins (1)
- pulmonary drug-delivery (1)
- pulmonary imaging (1)
- pulses (1)
- quanititative characterization (1)
- quantification (1)
- randomized clinical trial (1)
- reactive oxygen species (1)
- real time PCR (1)
- receptor type III (1)
- reflection (1)
- rekombinante Spinnseide (1)
- relaxometry (1)
- repair (1)
- replacement (1)
- respiratory syncytial virus (1)
- responses (1)
- retinal pigment epithelium (1)
- rhBMP–2 (1)
- ring-opening polymerization (1)
- salicylic acid (1)
- salivary gland neoplasia (1)
- salivary gland tumor (1)
- salivary gland tumors (1)
- salivary glands (1)
- scaffold (1)
- scanning electron microscopy (1)
- secondary lung tumors (1)
- secondary wound dressing (1)
- segmental collapse (1)
- sevoflurane (1)
- sheep model (1)
- signal integration (1)
- signal specification (1)
- signal tranduction (1)
- signal transduction (1)
- signaling (1)
- signaling pathways (1)
- site directed immobilization (1)
- site-specific immobilization (1)
- skin anatomy (1)
- skin equivalent (1)
- skin equivalents (1)
- skin model (1)
- skin models (1)
- skin physiology (1)
- small intestinal submucosa (1)
- small intestinal submucosa scaffold (1)
- sodium channels (1)
- sol-gel chemistry (1)
- solid tumors (1)
- solid tumour (1)
- solubility (1)
- sphingosine-1-phosphate (1)
- starch (1)
- stemness (1)
- sterubin (1)
- stimulation (1)
- stratification (1)
- stromal cells (1)
- stromal tissues (1)
- subfoveal choroidal neovascularization (1)
- subretinal space (1)
- superfamily (1)
- supermolecular carrier systems (1)
- surgical oncology (1)
- systemic inflammatory response syndrome (1)
- t-cell recruting antibody constructs (1)
- targeted combination therapy (1)
- technology (1)
- therapy simulation (1)
- tight junction (1)
- tissue culture (1)
- tissue model (1)
- tissue preparation (1)
- tissue remodeling (1)
- toxicity (1)
- toxicology (1)
- trachea (1)
- tracheal cytotoxin (1)
- trafficking (1)
- transcapillary pressure gradient (1)
- transcriptomics (1)
- transforming growth factor-beta 1 (1)
- translational research (1)
- translocation (1)
- transplantation (1)
- transport studies (1)
- tumor cells (1)
- tumor model systems (1)
- tumor test system (1)
- tumormicroenvironment (1)
- tumour (1)
- tumour microenvironment (1)
- tumour stroma (1)
- upcyte hepatocytes (1)
- validation (1)
- vascular normalization (1)
- vascular surgery (1)
- vascularized scaffold (1)
- vesicle-based barrier (1)
- viability (1)
- viral epidemiology (1)
- viral infection (1)
- virulence (1)
- weight-bearing (1)
- wound model (1)
- wound physiology (1)
- xenotransplantation (1)
- zielgerichtete Behandlung (1)
- zinc oxide nanoparticles (1)
- α-Cell (1)
- β-Cell (1)
Institute
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (155) (remove)
Sonstige beteiligte Institutionen
- Fraunhofer (1)
- Fraunhofer Institute Interfacial Engineering and Biotechnology (IGB) (1)
- Fraunhofer Institute for Integrierte Schaltungen (IIS) (1)
- IZKF (Interdisziplinäres Zentrum für Klinische Forschung), Universität Würzburg (1)
- Medizinische Universität Innsbruck (1)
- New York Blood Center (1)
- Queensland University of Technology (1)
Compared to cell therapy, where cells are injected into a defect region, the treatment of heart infarction with cells seeded in a vascularized scaffold bears advantages, such as an immediate nutrient supply or a controllable and persistent localization of cells. For this purpose, decellularized native tissues are a preferable choice as they provide an in vivo-like microenvironment. However, the quality of such scaffolds strongly depends on the decellularization process. Therefore, two protocols based on sodium dodecyl sulfate or sodium deoxycholate were tailored and optimized for the decellularization of a porcine heart. The obtained scaffolds were tested for their applicability to generate vascularized cardiac patches. Decellularization with sodium dodecyl sulfate was found to be more suitable and resulted in scaffolds with a low amount of DNA, a highly preserved extracellular matrix composition, and structure shown by GAG quantification and immunohistochemistry. After seeding human endothelial cells into the vasculature, a coagulation assay demonstrated the functionality of the endothelial cells to minimize the clotting of blood. Human-induced pluripotent-stem-cell-derived cardiomyocytes in co-culture with fibroblasts and mesenchymal stem cells transferred the scaffold into a vascularized cardiac patch spontaneously contracting with a frequency of 25.61 ± 5.99 beats/min for over 16 weeks. The customized decellularization protocol based on sodium dodecyl sulfate renders a step towards a preclinical evaluation of the scaffolds.
Cardiovascular diseases are considered the leading cause of death worldwide according to the World Health Organization. Heart failure is the last stage of most of these diseases, where loss of myocardium leads to architectural and functional decline.
The definitive treatment option for patients with CVDs is organ or tissue transplantation, which relies on donor availability. Therefore, generating an autologous bioengineered myocardium or heart could overcome this limitation. In addition, generating cardiac patches will provide ventricular wall support and enable reparative stem cells delivery to damaged areas. Although many hurdles still exist, a good number of researches have attempted to create an engineered cardiac tissue which can induce endogenous cardiac repair by replacing damaged myocardium.
The present study provided cardiac patches in two models, one by a detergent coronary perfusion decellularization protocol that was optimized, and the other that resulted in a 3D cell-free extracellular matrix with intact architecture and preserved s-glycosaminoglycan and vasculature conduits. Perfusion with 1% Sodium dodecyle sulfate (SDS) under constant pressure resulted in cell-free porcine scaffold within two and cell-free rat scaffold in 7 days, whereas scaffold perfused with 4% sodium deoxycholate (SDO) was not able to remove cells completely. Re-reendothelialization of tissue vasculature was obtained by injecting human microvascular endothelial cell and human fibroblast in 2:1 ratio in a dynamic culture. One-week later, CD31 positive cells and endothelium markers were observed, indicating new blood lining. Moreover, functionality test of re-endothelialized tissue revealed improvement in clotting seen in decellularized tissues. When the tissue was ready to be repopulated, porcine induced pluripotent stem cells (PiPSc) were generated by transfected reprogramming of porcine skin fibroblast and then differentiated to cardiac cells following a robust protocol, for an autologous cardiac tissue model. However, due to the limitation in the PiPSc cell number, alternatively, human induced pluripotent stem cells generated cardiac cells were used.
For reseeding a coculture of human iPSc generated cardiac cells, human mesenchymal stem cells and human fibroblast in 2:1:1 ratio respectively were used in a dynamic culture for 6-8 weeks. Contractions at different areas of the tissue were recorded at an average beating rate of 67 beats/min. In addition, positive cardiac markers (Troponin T), Fibroblast (vemintin), and mesenchymal stem cells (CD90) were detected. Not only that, but by week 3, MSC started differentiating to cardiac cells progressively until few CD90 positive cells were very few by week 6 with increasing troponin t positive cells in parallel. Electrophysiological and drug studies were difficult to obtain due to tissue thickness and limited assessment sources. However, the same construct was established using small intestine submucosa (SISer) scaffold, which recorded a spontaneous beating rate between 0.88 and 1.2 Hz, a conduction velocity of 23.9 ± 0.74 cm s−1, and a maximal contraction force of 0.453 ± 0.015 mN. Moreover, electrophysiological studies demonstrated a drug-dependent response on beating rate; a higher adrenalin frequency was revealed in comparison to the untreated tissue and isoproterenol administration, whereas a decrease in beating rate was observed with propranolol and untreated tissue.
The present study demonstrated the establishment of vascularized cardiac tissue, which can be used for human clinical application.
Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.
The Gram-negative Epsilonproteobacterium Campylobacter jejuni is currently the most prevalent bacterial foodborne pathogen. Like for many other human pathogens, infection studies with C. jejuni mainly employ artificial animal or cell culture models that can be limited in their ability to reflect the in-vivo environment within the human host. Here, we report the development and application of a human three-dimensional (3D) infection model based on tissue engineering to study host-pathogen interactions. Our intestinal 3D tissue model is built on a decellularized extracellular matrix scaffold, which is reseeded with human Caco-2 cells. Dynamic culture conditions enable the formation of a polarized mucosal epithelial barrier reminiscent of the 3D microarchitecture of the human small intestine. Infection with C. jejuni demonstrates that the 3D tissue model can reveal isolate-dependent colonization and barrier disruption phenotypes accompanied by perturbed localization of cell-cell junctions. Pathogenesis-related phenotypes of C. jejuni mutant strains in the 3D model deviated from those obtained with 2D-monolayers, but recapitulated phenotypes previously observed in animal models. Moreover, we demonstrate the involvement of a small regulatory RNA pair, CJnc180/190, during infections and observe different phenotypes of CJnc180/190 mutant strains in 2D vs. 3D infection models. Hereby, the CJnc190 sRNA exerts its pathogenic influence, at least in part, via repression of PtmG, which is involved in flagellin modification. Our results suggest that the Caco-2 cell-based 3D tissue model is a valuable and biologically relevant tool between in-vitro and in-vivo infection models to study virulence of C. jejuni and other gastrointestinal pathogens.
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.
Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood‐brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono‐ or (isogenic) co‐culture BBB models based on brain capillary endothelial cells (BCECs) derived from human‐induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non‐human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco‐2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC‐derived BBB models could impact future discovery and development of novel CNS‐targeting therapeutics.
Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.
To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.
Cancer remains after cardiovascular diseases the leading cause of death worldwide and an estimated 8.2 million people died of it in 2012. By 2030, 13 million cancer deaths are expected due to the growth and ageing of the population. Hereof, colorectal cancer (CRC) is the third most common cancer in men and the second in women with a wide geographical variation across the world. Usually, CRC begins as a non-cancerous growth leading to an adenomatous polyp, or adenoma, arising from glandular cells. Since research has brought about better understanding of the mechanisms of cancer development, novel treatments such as targeted therapy have emerged in the past decades. Despite that, up to 95% of anticancer drugs tested in clinical phase I trials do not attain a market authorisation and hence these high attrition rates remain a key challenge for the pharmaceutical industry, making drug development processes enormously costly and inefficient. Therefore, new preclinical in vitro models which can predict drug responses in vivo more precisely are urgently needed. Tissue engineering not only provides the possibility of creating artificial three-dimensional (3D) in vitro tissues, such as functional organs, but also enables the investigation of drug responses in pathological tissue models, that is, in 3D cancer models which are superior to conventional two-dimensional (2D) cell cultures on petri dishes and can overcome the limitations of animal models, thereby reducing the need for preclinical in vivo models. In this thesis, novel 3D CRC models on the basis of a decellularised intestinal matrix were established. In the first part, it could be shown that the cell line SW480 exhibited different characteristics when grown in a 3D environment from those in conventional 2D culture. While the cells showed a mesenchymal phenotype in 2D culture, they displayed a more pronounced epithelial character in the 3D model. By adding stromal cells (fibroblasts), the cancer cells changed their growth pattern and built tumour-like structures together with the fibroblasts, thereby remodelling the natural mucosal structures of the scaffold. Additionally, the established 3D tumour model was used as a test system for treatment with standard chemotherapeutic 5-fluorouracil (5-FU). The second part of the thesis focused on the establishment of a 3D in vitro test system for targeted therapy. The US Food and Drug Administration has already approved of a number of drugs for targeted therapy of specific types of cancer. For instance, the small molecule vemurafenib (PLX4032, Zelboraf™) which demonstrated impressive response rates of 50–80% in melanoma patients with a mutation of the rapidly accelerated fibrosarcoma oncogene type B (BRAF) kinase which belongs to the mitogen active protein kinase (MAPK) signalling pathway. However, only 5% of CRC patients harbouring the same BRAF mutation respond to treatment with vemurafenib. An explanation for this unresponsiveness could be a feedback activation of the upstream EGFR, reactivating the MAPK pathway which sustains a proliferative signalling. To test this hypothesis, the two early passage cell lines HROC24 and HROC87, both presenting the mutation BRAF V600E but differing in other mutations, were used and their drug response to vemurafenib and/or gefitinib was assessed in conventional 2D cell culture and compared to the more advanced 3D model. Under 3D culture conditions, both cell lines showed a reduction of the proliferation rate only in the combination therapy approach. Furthermore, no significant differences between the various treatment approaches and the untreated control regarding apoptosis rate and viability for both cell lines could be found in the 3D tumour model which conferred an enhanced chemoresistance to the cancer cells. Because of the observed unresponsiveness to BRAF inhibition by vemurafenib as can be seen in the clinic for patients with BRAF mutations in CRC, the cell line HROC87 was used for further xenografting experiments and analysis of activation changes in the MAPK signalling pathway. It could be shown that the cells presented a reactivation of Akt in the 3D model when treated with both inhibitors, suggesting an escape mechanism for apoptosis which was not present in cells cultured under conventional 2D conditions. Moreover, the cells exhibited an activation of the hepatocyte growth factor receptor (HGFR, c-Met) in 2D and 3D culture, but this was not detectable in the xenograft model. This shows the limitations of in vivo models. The results suggest another feedback activation loop than that to the EGFR which might not primarily be involved in the resistance mechanism. This reflects the before mentioned high attrition rates in the preclinical drug testing.
Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue.