Institute of Experimental Medicine CAS

The research of the Department is focused on the development of artificial tissues, mainly biodegradable scaffolds for tissue regeneration, such as nanofibers, foams, and hydrogels for the regeneration of cartilage, bone and incisional hernia. We also focus on computer modeling of protein structures. We are developing the technology of controlled drug delivery from nanofibers scaffolds with liposomes for targeted release of drugs into the defect. The work is also concentrated on the development of three-dimensional nanofibers, using novel technique of Forcespinning®. These nanofibres are more suitable for cell growth and differentiation. Moreover, high on our priority list is also the accelerated transfer of newly developed technologies and know-how into clinical practice. We are developing artificial scaffolds for the regeneration of bone and cartilage in clinical practice.

Deputy Head:

Lucie Wolfová, Dipl. Ing., PhD.
E-mail: lucie.wolfova@iem.cas.cz
Phone: +420 241 063 367

Research Scientists:

Eva Filová, MSc, PhD.
Michala Rampichová, MSc, PhD.
Lucie Wolfová, Dipl. Ing., PhD.
Andrea Staffa, MSc, PhD. (ML)
Jana Daňková, MSc, PhD. (ML)
Věra Hedvičáková, MSc, PhD.
 Věra Sovková, MSc, PhD. (ML)
Karolína Vocetková, MD et Dipl. Ing., PhD.
Gracián Tejral, MSc, PhD.
Bruno Sopko, PhD.

PhD. Students:

Radek Divín, MSc.
Barbora Voltrová, MSc (ML)
Veronika Hefka Blahnová, MSc.
Radmila Žižková, MSc.
Eva Šebová, MSc.

Undergraduate Students:

Erna Šljivnjak, Bc.
Eliška Krčmářová, Bc.

Technican:

Lenka Uherková, MSc, PhD.

Important results in 2020

 
1.  We tested nanostructured β-titanium alloy Ti-36Nb-6Ta for stimulation of osteogenic differentiation of human mesenchymal stem cells

We evaluated the impact of a nanotubes, with average diameters 18, 36 and 46 nm, created by anodic oxidation on the surface β-titanium alloy, Ti-36Nb-6Ta, on the growth and differentiation of human mesenchymal stem cells. The nanotubes lowered elastic modulus close to that of bone, positively influenced cell adhesion and osteogenic differentiation (improved ALP activity, synthesis of type I collagen and osteocalcin expression). Ti-36Nb-6Ta with nanotube diameters 36 nm was the most promising material for bone implantation.

obr-1-2020

Visualization of human mesenchymal stem cells adhered on nanotubes created on Ti-36Nb-6Ta by anodic oxidation at 10, 20 and 30V 24 h after seeding using scanning electron microscope

obr-2-2020

Visualization of hMSCs adhered on β-titanium alloy Ti-36Nb-6Ta nanostructured using anodic oxidation at 10V, 20V and 30V using confocal microscopy

 
2.  We tested 3D printed composites for bone tissue engineering 

We tested 3D printing of biocompatible PHB/PLA-based scaffold prepared using the FDM technique. Four different materials (or filaments) with tricalciumphosphate (TCP) fillers and two different plasticizers, Citroflex and Syncroflex, were prepared. The effects of TCP fillers and plasticizer on thermal and mechanical properties of the materials were observed. Moreover, their effects on printability, biocompatibility, and mesenchymal stem cell osteogenic differentiation were examined.

obr-3-2020

Visualization of osteocalcin, protein typical for bone tissue, produced by cells seeded on scaffolds using confocal microscopy

 

Important results in 2019

 
1. We tested composite scaffolds from collagen, chitosan and bovine lysate for the regeneration of soft tissues

We tested foam scaffolds from cross-linked type I collagen with the addition of chitosan/Ca salt of oxidize cellulose/chitin-chitosan-glucan complex and bovine lysate. The scaffold containing polysaccharides and bovine lysate significantly increased metabolic activity of mouse 3T3 fibroblasts. The scaffold containing collagen/chitosan/bovine lysate exhibited the most enhanced cell proliferation. Moreover, the scaffolds containing collagen/bovine lysate showed a positive effect on angiogenesis compared to the plain collagen scaffold.

obr-1-2019

SEM images of all prepared crosslinked collagen sponges with various additives and pore size evaluation

obr-2-2019

Metabolic activity (A) and proliferation (B) of 3T3 fibroblasts on composite collagen foam scaffolds 

 
2. We prepared platelet-functionalized 2D electrospun and 3D centrifugal spun polycaprolactone scaffolds and observed their influence on growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs)

We prepared scaffolds from poly-ε-caprolactone using electrospinning and centrifugal spinning technology and modified them with five platelet concentrations. The 3D structure of fibers resulted in higher cell proliferation. The platelets addition resulted in a dose-dependent increase in cell metabolic activity, proliferation and production of alkaline phosphatase. The osteoconductive effect was further promoted by osteogenic supplements in culture medium.

obr-3-2019

Fibrous scaffolds prepared using electrospinning (ES) and centrifugal spinning (CS) with adhered platelets visualized using scanning electron microscopy

obr-4-2019

ALP activity of hMSCs seeded on scaffolds prepared using electrospinning and centrifugal spinning technology was dose-dependently influenced by platelets

 

Important results in 2018

 
1. We Identified eukaryotic translation elongation factor 1‑α 1 gamendazole-binding site for binding of 3‑hydroxy-4(1H)‑quinolinones and synthetiised novel ligands with anticancer activity

We have successfully identified the interaction site of the contraceptive drug gamendazole using computational modelling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We have designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to prove that these compounds strongly bind to eEF1A1. Moreover, we found that some of these derivatives possess significant in vitro anticancer activity.

obr-1-2018

The interaction site of gamendazole with eukaryotic translation elongation factor 1-α 1 (eEF1A1). The interaction of gamendazole (red) with eEF1A1. The parts of eEF1A1 previously identified to be in contact with gamendazole are in green (being in agreement with our in silico experiment) and yellow – not confirmed by us.

 
2. We modified polypropylene mesh for regeneration of incisional hernia with poly-ε-caprolacton nanofibers

We prepared a composite scaffold that was assembled out of a standard polypropylene hernia mesh and poly-ε-caprolactone (PCL) nanofibers and tested it in a large animal model of incisional hernia (minipig). The histological and biomechanical examination showed that a layer of PCL nanofibers leads to tissue overgrowth and the formation of a thick fibrous plate around the implant. Collagen maturation was accelerated, and the final scar was more flexible and elastic than under a standard polypropylene mesh with less pronounced shrinkage observed. However, the samples with the composite scaffold were less resistant to distracting forces than when a standard mesh was used. 

obr-2-2018

Histological evaluation of incision and area without incision. The stitches (S) of PP samples were surrounded by the infiltrated with inflammatory cells (I). The PP/PCL sample contains a smaller number of actin-positive vessels (red arrows), greater fraction of actin-positive myofibroblasts (M) and collagen type I (C) at the incision areas. 

 

Important results in 2017

 

1.Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells (MSCs) differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells

We developed self-assembling nanoparticles encapsulating zoledronic acid (NZ) that allowed a higher intratumor delivery of the drug compared with free zoledronic acid in in vivo cancer models of prostate cancer ( PCa). The treatment with NZ decreased migration and differentiation into adipocytes and osteoblasts of MSCs and inhibited secretion of proangiogenic factors.  In conclusion, NZ was capable to inhibit the cross talk between MSCs and PCa which explain the anticancer activity of NZ on PCa.

 

filova-2017-1

Treatment of MSCs with nanoparticles encapsulating zoledronic acid (NZ)  or treatment with zoledronic acid solution (ZA) decreased the clonogenic growth of prostate cancer cells 3 (PC3) induced by conditioned medium of MSCs (MSC-CM). 100 PC3 cells were plated in 24-well flat-bottomed plates and allowed to adhere for 24 h, then cultured in the presence of increased concentrations of supernatants from MSCs untreated or treated with ZA or NZ (20 μM). After 7 days, plates were observed under phase-contrast microscopy and colonies counted. Values represent the mean ± SD of N=3 independent experiments.

 

2.Platelet-functionalized three-dimensional poly-Ɛ-epsilon-caprolactone fibrous scaffold prepared using centrifugal spinning for delivery of growth factors.

PCL three-dimensional fibrous meshes prepared via centrifugal spinning were combined with adhered platelets of five different concentrations. Released growth factors supported cell proliferation and metabolic activity of MG-63 cells in concentrations higher than physiological (300×109/L). Lower concentrations of platelets were not supportive and were comparable to control. Similarly, alkaline phosphatase activity was increased on samples with two most concentrated platelets concentrations.

filova-2017-2

Platelets adhered on poly- ε-caprolactone fibers. SEM visualization of platelet adhesion on PCL fibers. Platelets were partially activated and formed a fibrin net 24 h after adhesion (A). Platelets were visibly adhered on fibers even after 14 days of the experiment (B).

 

3. Osteogenic differentiation of 3D cultured mesenchymal stem cells induced by bioactive peptides

The present study focuses on comparison of bioactive peptides as osteogenesis promoting factor. The chosen peptides were derived from receptor binding sequences of collagen III, BMP-7 and BMP-2. BMP-2 peptide has the best potential to induce osteogenic differentiation of pMSCs.

filova-2017-3

Expression of osteocalcin gene. The expression level of osteocalcin, which is a late marker of osteogenic differentiation, was detected on days 7 and 14. The abbreviations above the bars denote to statistical difference with P < 0.05. Abbreviations: MSCs, mesenchymal stem cells; OCN, osteocalcin; aminoacid sequences: I, IAGVGGEKSGGF; G, GQGFSYPYKAVFSTQ; K, KIPKASSVPTELSAISTLYL; 1, 1 μg/mL concentration of peptides; 5, μg/mL; 10, μg/mL; Cn, control group (with no peptides added).

 

Important results in 2015

 
1. We have developed dispersion nanofibers from poly-ε-caprolactone enriched with magnetic nanoparticles prepared by needleless electrospinning

The nanofibers enhanced adhesion and osteogenic proliferation of pig mesenchymal stem cells and are promising for bone regeneration. (Daňková et al. 2015).

amler2015-1

Scanning electron microscopy of the poly-ε-caprolactone nanofiber scaffold with magnetic nanoparticles.

 
2. We have developed polypropylene (PP) surgical mesh coated with PCL nanofibers with adhered thrombocytes as natural source of growth factors

The composite mesh with thrombocytes showed improved fibroblasts adhesion, proliferation, and metabolic activity compared to PP, PP coated with nanofibers, and PP functionalized with thrombocytes. The system of composite scaffold with growth factors released from thrombocytes is promising approache for tissue engineering.

amler2015-2

Scanning electron microscopy of the implanted scaffolds. (A) PCL nanofibers; (B) PP mesh; (C) PP mesh functionalized with PCL nanofibers.

3. Nanofibers from polyvinyl alcohol (PVA) were functionalized by polyethylene glycol with biotin (PEG-b) linker and sequence-specific binding of avidin- antibody conjugate

PEG-b functionalized nanofibers significantly decreased nanofiber decay in a controlled manner. Moreover, the binding of anti CD-29 antibody to PEG-b linker stimulated mesenchymal stem cell adhesion to PVA-PEG-b nanofibers through β1-integrin receptor. The second system of the selective protein binding on the nanofiber surface represented anti-transferrin-PEG-b nanofibers.

amler2015-3

Photomicrograph and schema of nanofibers from polyvinylalcohol (PVA) functionalized with polyethylene glycol with biotin (PEG-b) linker and sequence-specific binding of avidin- antibody (anti-transferin) conjugate.

 

 Important results in 2014

 

1. Functionalized nanofibers for controlled drug delivery

The system of functionalized nanofibers with controlled drug delivery has been developed and optimized. This system has been applied for treatment of incisional hernia. Polypropylene surgical mesh was modified by PCL nanofibers covering and functionalised with adhesion of growth factors. Samples were tested in vivo on a rabbit model as a model for prevention of incisional hernia formation.

amler2014-1

Scanning electron microscopy of the scaffolds used for the abdominal closure. Notes: (A) nanofibers from poly-ε-caprolactone (magnification 230×); (B) polypropylene mesh (magnification 18×); (C) polypropylene mesh functionalized with poly-ε-caprolactone nanofibers (magnification 18×).

 

2. Biomechanical testing of the repaired abdominal wall

Abdominal closure was reinforced by application of polypropylene mesh functionalized with poly-ε-caprolactone nanofibers and growth factors. This novel arrangement is going to be used for prevention of incisional hernia formation. However, the system seems to be very general and there is intended for much broader chirurgical and orthopedical application.

amler2014-2

Images of carriers used for closure of abdominal incision switched by scanning electron microscopy. (A) nanofibers of poly-ε-caprolactone (magnification × 230), (B) polypropylene mesh (18 × magnification), (C) polypropylene mesh using functionalized nanofibers of poly-ε-caprolactone.

amler2014-3

Histological evaluation. Collagen, adipose tissue, and granulomatous infiltration in the scaffolds under study. In samples without any mesh (A), the incision was healing with a mixture of collagen (black arrow), adipose connective tissue (red arrow) and inflammatory infiltrate (yellow arrow). Samples with polypropylene (PP) mesh (B) had a high fraction of adipose tissue, but the spaces showing the dissolved mesh (black arrows) were surrounded by only a few inflammatory cells. Remnants of the nanofibers (C, D, E, F) were surrounded by granulomatous leukocyte-rich connective tissue (yellow arrows in C, D, E, F). The highest fraction of collagen (red arrow) was in samples of PCL nanofibers with adhered growth factors (GF) (D), followed by samples with no mesh (A) and by samples of PCL nanofibers (F). Low fractions of adipose tissue were found in samples of PCL nanofibers with adhered GF (D), samples with no mesh (A) and in samples of PCL nanofibers (F).

2021

Hedvičáková, V., Žižková, R., Buzgo, M., Rampichová, M., & Filová, E.  (2021). The Effect of Alendronate on Osteoclastogenesis in Different Combinations of M-CSF and RANKL Growth Factors. Biomolecules11(3), 438. 

2020

Hefka Blahnova, V., Dankova, J., Rampichova, M., & Filova, E.  (2020). Combinations of growth factors for human mesenchymal stem cell proliferation and osteogenic differentiation. Bone & joint research9(7), 412–420.

Jarolimova, P., Voltrova, B., Blahnova, V., Sovkova, V., Pruchova, E., Hybasek, V., Fojt, J., Filova, E. (2020). Mesenchymal stem cell interaction with Ti6Al4V alloy pre-exposed to simulated body fluid. RSC ADVANCES, 10(12), 6858-6872 

Voltrova, B.,  Jarolimova, P., Hybasek, V., Blahnova, V. H., Sepitka, J., Sovkova, V., Matějka, R., Daniel, M., Fojt, J., & Filova, E. (2020). In vitro evaluation of a novel nanostructured Ti-36Nb-6Ta alloy for orthopedic applications. Nanomedicine (London, England)15(19), 1843–1859. 

Filová, E.,  Tonar, Z., Lukášová, V., Buzgo, M., Litvinec, A., Rampichová, M., Beznoska, J., Plencner, M., Staffa, A., Daňková, J., Soural, M., Chvojka, J., Malečková, A., Králíčková, M., & Amler, E. (2020). Hydrogel Containing Anti-CD44-Labeled Microparticles, Guide Bone Tissue Formation in Osteochondral Defects in Rabbits. Nanomaterials (Basel, Switzerland)10(8), 1504. 

Vocetkova, K., Sovkova, V., Buzgo, M., Lukasova, V., Divin, R., Rampichova, M.,  Blazek, P., Zikmund, T., Kaiser, J., Karpisek, Z., Amler, E., & Filova, E. (2020). A Simple Drug Delivery System for Platelet-Derived Bioactive Molecules, to Improve Melanocyte Stimulation in Vitiligo Treatment. Nanomaterials (Basel, Switzerland)10(9), 1801. 

Melčová, V., Svoradová, K., Menčík, P., Kontárová, S., Rampichová, M., Hedvičáková, V., Sovková, V., Přikryl, R., & Vojtová, L. (2020). FDM 3D Printed Composites for Bone Tissue Engineering Based on Plasticized Poly(3-hydroxybutyrate)/poly(d,l-lactide) Blends. Polymers12(12), 2806. 

Zhu, H., Blahnová, V. H., Perale, G., Xiao, J., Betge, F., Boniolo, F., Filová, E., Lyngstadaas, S. P., & Haugen, H. J. (2020). Xeno-Hybrid Bone Graft Releasing Biomimetic Proteins Promotes Osteogenic Differentiation of hMSCs. Frontiers in cell and developmental biology8, 619111. 

Frtús, A., Smolková, B., Uzhytchak, M., Lunova, M., Jirsa, M., Hof, M., Jurkiewicz, P., Lozinsky, V. I., Wolfová, L., Petrenko, Y., Kubinová, Š., Dejneka, A., & Lunov, O. (2020). Hepatic Tumor Cell Morphology Plasticity under Physical Constraints in 3D Cultures Driven by YAP-mTOR Axis. Pharmaceuticals (Basel, Switzerland)13(12), 430.

2019

Vojtova, L., Michlovska, L., Valova, K., Zboncak, M., Trunec, M., Castkova, K., Krticka, M., Pavlinakova, V., Polacek, P., Dzurov, M., Lukasova, V., Rampichova, M., Suchy, T., Sedlacek, R., Ginebra, M. P., & Montufar, E. B. (2019). The Effect of the Thermosensitive Biodegradable PLGA⁻PEG⁻PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement. International journal of molecular sciences20(2), 391. 

Buzgo, M., Plencner, M., Rampichova, M., Litvinec, A., Prosecka, E., Staffa, A., Kralovic, M., Filova, E.,  Doupnik, M., Lukasova, V., Vocetkova, K., Anderova, J., Kubikova, T., Zajicek, R., Lopot, F., Jelen, K., Tonar, Z.,Amler, E., Divin, R., Fiori, F. (2019). Poly-ε-caprolactone and polyvinyl alcohol electrospun wound dressings: adhesion properties and wound management of skin defects in rabbits. Regenerative Medicine.14(5):423-445.

Stastny, P., Sedlacek, R., Suchy, T., Lukasova, V., Rampichova, M., & Trunec, M. (2019). Structure degradation and strength changes of sintered calcium phosphate bone scaffolds with different phase structures during simulated biodegradation in vitro. Materials science & engineering. C, Materials for biological applications100, 544–553. 

Lukášová, V., Buzgo, M., Vocetková, K., Sovková, V.,  Doupník, M., Himawan, E., Staffa, A., Sedláček, R., Chlup, H., Rustichelli, F., Amler, E., & Rampichová, M. (2019). Needleless electrospun and centrifugal spun poly-ε-caprolactone scaffolds as a carrier for platelets in tissue engineering applications: A comparative study with hMSCs. Materials science & engineering. C, Materials for biological applications97, 567–575. 

Voltrova, B.,  Hybasek, V., Blahnova, V., Sepitka, J., Lukasova, V., Vocetkova, K., Sovkova, V., Matejka, R., Fojt, J., Joska, L., Daniel, M., Filova, E. (2019). Different diameters of titanium dioxide nanotubes modulate Saos-2 osteoblast-like cell adhesion and osteogenic differentiation and nanomechanical properties of the surface. RSC ADVANCES  9(20), 11341-11355.  

East, B., Plencner, M., Otahal, M., Amler, E., & de Beaux, A. C. (2019). Dynamic creep properties of a novel nanofiber hernia mesh in abdominal wall repair. Hernia : the journal of hernias and abdominal wall surgery23(5), 1009–1015. 

Babrnáková, J., Pavliňáková, V., Brtníková, J., Sedláček, P., Prosecká, E., Rampichová, M., Filová, E., Hearnden, V., & Vojtová, L. (2019). Synergistic effect of bovine platelet lysate and various polysaccharides on the biological properties of collagen-based scaffolds for tissue engineering: Scaffold preparation, chemo-physical characterization, in vitro and ex ovo evaluation. Materials science & engineering. C, Materials for biological applications100, 236–246.

2018

Horakova, J., Mikes, P., Lukas, D., Saman, A., Jencova, V., Klapstova, A., Svarcova, T., Ackermann, M., Novotny, V., Kalab, M., Lonsky, V., Bartos, M., Rampichova, M., Litvinec, A., Kubikova, T., Tomasek, P., & Tonar, Z. (2018). Electrospun vascular grafts fabricated from poly(L-lactide-co-ε-caprolactone) used as a bypass for the rabbit carotid artery. Biomedical materials (Bristol, England)13(6), 065009. 

Alaia, C., Boccellino, M., Zappavigna, S., Amler, E., Quagliuolo, L., Rossetti, S., Facchini, G., & Caraglia, M. (2018). Ipilimumab for the treatment of metastatic prostate cancer. Expert opinion on biological therapy18(2), 205–213. 

Zaviskova, K., Tukmachev, D., Dubisova, J., Vackova, I., Hejcl, A., Bystronova, J., Pravda, M., Scigalkova, I., Sulakova, R., Velebny, V., Wolfova, L., & Kubinova, S. (2018). Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair. Journal of biomedical materials research. Part A106(4), 1129–1140. 

Burglová, K., Rylová, G., Markos, A., Prichystalova, H., Soural, M., Petracek, M., Medvedikova, M., Tejral, G., Sopko, B., Hradil, P., Dzubak, P., Hajduch, M., & Hlavac, J. (2018). Identification of Eukaryotic Translation Elongation Factor 1-α 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1 H)-quinolinones as Novel Ligands with Anticancer Activity. Journal of medicinal chemistry61(7), 3027–3036. 

East, B., Plencner, M., Kralovic, M., Rampichova, M., Sovkova, V., Vocetkova, K., Otahal, M., Tonar, Z., Kolinko, Y., Amler, E., & Hoch, J. (2018). A polypropylene mesh modified with poly-ε-caprolactone nanofibers in hernia repair: large animal experiment. International journal of nanomedicine13, 3129–3143. 

Lukasova, V.,  Buzgo, M., Vocetkova, K., Kubikova, T., Tonar, Z., Doupnik, M., Blahnova, V., Litvinec, A., Sovkova, V., Voltrova, B., Staffa, A., Svora, P., Kralickova, M., Amler, E., Filova, E., Rustichelli, F., Rampichova, M. (2018) Osteoinductive 3D scaffolds prepared by blend centrifugal spinning for long-term delivery of osteogenic supplements. RSC ADVANCES, 8(39), 21889-21904

2017

Borghese, C., Casagrande, N., Pivetta, E., Colombatti, A., Boccellino, M., Amler, E., Normanno, N., Caraglia, M., De Rosa, G., Aldinucci, D.: (2017) Self-assembling nanoparticles encapsulating zoledronic acid inhibit mesenchymal stromal cells differentiation, migration and secretion of proangiogenic factors and their interactions with prostate cancer cells. OncoTarget. 8 (26): 42926-42938.

Buzgo, M., Rampichová, M., Vocetková, K., Sovková, V., Lukášová, V., Doupnik, M., Míčková, A., Rustichelli, F., Amler, E.: (2017) Emulsion centrifugal spinning for production of 3D drug releasing nanofibres with core/shell structure. RSC Advances. 7(3): 1215-1228.

Buzgo, M., Filová, E., Staffa, A., Rampichová, M.  , Doupnik, M., Vocetková, K., Lukášová, V., Kolcun, R., Lukáš, D., Nečas, A., Amler, E.: (2017) Needleless emulsion electrospinning for the regulated delivery of susceptible proteins. Journal of Tissue Engineering and Regenerative Medicine. May 16. doi: 10.1002/term.2474. [Epub ahead of print]

Gregor, A., Filová, E., Novák, M., Kronek, J., Chlup, H., Buzgo, M., Blahnová, V., Lukášová, V., Bartoš, M., Nečas, A., Hošek, J.: (2017) Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer. Journal of Biological Engineering. 11: 31.

Hadraba, D., Janáček, J., Filová, E., Lopot, F., Paesen, R., Fanta, O., Jarman, A., Nečas, A., Ameloot, M., Jelen, K.: (2017) Calcaneal Tendon Collagen Fiber Morphometry and Aging. Microscopy and Microanalysis. 23 (5): 1040-1047.

Lukášová, V., Buzgo, M., Sovková, V., Daňková, J., Rampichová, M., Amler, E.: (2017)  Osteogenic differentiation of 3D cultured mesenchymal stem cells induced by bioactive peptides. Cell Proliferation. 50 (4): e12357.

Paino, F., Noce, M.L., Giuliani, A., de Rosa, A., Mazzoni, F., Laino, L., Amler, E., Papaccio, G., Desiderio, V., Tirino, V.: (2017) Human DPSCs fabricate vascularized woven bone tissue: A new tool in bone tissue engineering. Clinical science. 131(8): 699-713.

Rampichová, M.,  Buzgo, M., Míčková, A., Vocetková, K., Sovková, V., Lukášová, V., Filová, E., Rustichelli, F., Amler, E.: (2017) Platelet-functionalized three-dimensional polye-epsilon-caprolactone fibrous scaffold prepared using centrifugal spinning for delivery of growth factors. International Journal of Nanomedicine. 12:347-361.

Rampichová, M.  , Chvojka, J., Jenčová, V., Kubíková, T., Tonar, Z., Erben, J., Buzgo, M., Daňková, J., Litvinec, A., Vocetková, K., Plencner, M., Prosecká, E., Sovková, V., Lukášová, V., Králíčková, M., Lukáš, D., Amler, E.: (2017) The combination of nanofibrous and microfibrous materials for enhancement of cell infiltration and in vivo bone tissue formation. Biomedical Materials. IN PRESS

Rampichová, M.  , Kuželová Košťáková, E., Filová, E., Chvojka, J., Šafka, J., Pelcl, M., Daňková, J., Prosecká, E., Buzgo, M., Plencner, M., Lukáš, D., Amler, E.: (2017) Composite 3D printed scaffold with structured electrospun nanofibers promotes chondrocyte adhesion and infiltration. Cell Adhesion and Migration. Nov 13:1-15. doi: 10.1080/19336918.2017.1385713. [Epub ahead of print]

Sovková, V., Vocetková, K., Rampichová, M., Míčková, A., Buzgo, M., Lukášová, V., Daňková, J., Filová, E.  , Nečas, A., Amler, E.: (2017) Platelet lysate as a serum replacement for skin cell culture on biomimetic PCL nanofibers. Platelets. Jun 26:1-11. doi: 10.1080/09537104.2017.1316838. [Epub ahead of print]

Szöke, K., Daňková, J., Buzgo, M., Amler, E., Brinchmann, J.E., Østrup, E.: (2017) The effect of medium composition on deposition of collagen type 1 and expression of osteogenic genes in mesenchymal stem cells derived from human adipose tissue and bone marrow. Process Biochemistry. 59(B): 321-328.

Tejral, G.,  Sopko, B., Nečas, A., Schoner, W., Amler, E.: (2017) Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump. PeerJ. 5: 3087.

Vocetková, K.  , Buzgo, M., Sovková, V., Rampichová, M., Staffa, A., Filová, E., Lukášová, V., Doupnik, M., Fiori, F., Amler, E.: (2017) A comparison of high throughput core–shell 2D electrospinning and 3D centrifugal spinning techniques to produce platelet lyophilisate-loaded fibrous scaffolds and their effects on skin cells. RSC Advances. 7(85): 53706-53719.

Vysloužilová, L., Buzgo, M., Pokorný, P., Chvojka, J., Míčková, A., Rampichová, M., Kula, J., Pejchar, K., Bílek, M., Lukáš, D., Amler, E.: (2017) Needleless coaxial electrospinning: A novel approach to mass production of coaxial nanofibers. International Journal of Pharmaceutics. 516(1-2):293-300.

2016

Smyslová, P., Popa, I., Lyčka, A., Tejral, G., Hlaváč, J.:(2016) Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles. PLoS One., 10(12): e0144613.

Filová, E., Jakubcová, B.  , Danilová, I., Kuželová Košťáková, E., Jarošíková, T., Chernyavskiy, O., Hejda, J., Handl, M., Beznoská, J., Nečas, A., Rosina, J., Amler, E.: (2016) Polycaprolactone foam functionalized with chitosan microparticles - a suitable scaffold for cartilage regeneration. Physiol. Res., 65(1): 121-131.

Vocetková, K., Buzgo, M., Sovková, V., Bezděková, D.  , Kneppo, P., Amler, E.: (2016) Nanofibrous polycaprolactone scaffolds with adhered platelets stimulate proliferation of skin cells. Cell Prolif., 49(5):568-78.

2015

Buzgo, M., Greplová, J., Soural, M., Bezděková, D., Míčková, A., Kofroňová, O., Benada, O., Hlaváč, J., Amler, E.: (2015) PVA immunonanofibers with controlled decay. Polymer. 7: 387-398.

Daňková, J., Buzgo, M., Vejpravová, J., Kubíčková, S., Sovková, V., Vysloužilová, L., Mantlíková, A., Nečas, A., Amler, E.: Highly efficient mesenchymal stem cell proliferation on poly-ε-caprolactone nanofibers with embedded magnetic nanoparticles. Int J Nanomedicine. 10:7307-17.

Erben, J., Pilarová, K., Sanetrnik, F., Chvojka, J., Jenčová, V., Blažková, L., Havlíček, J., Novák, O., Mikeš, P., Prosecká, E., Lukaš, D., Kuzelová Kostaková E.: (2015) The combination of meltblown and electrospinning for bone tissue engineering. Materials Letters 143, 172-176.

Filová, E., Jakubcová, B., Danilová, I., Kuželová Košťáková, E., Jarošíková, T., Chernyavskiy, O., Hejda, J., Handl, M., Beznoská, J., Nečas, A., Rosina, J., Amler, E.: (2015) Polycaprolactone foam functionalized with chitosan microparticles - a suitable scaffold for cartilage regeneration. Physiol Res. IN PRESS

Kubíková, T., Filová, E., Prosecká, E., Plencner, M., Králíčková, M., Tonar, Z.: (2015) Histological evaluation of biomaterials administration in vivo on the cartilage, bone and skin healing. Cas Lek Cesk., 154(3):110-4.

Plencner, M., Prosecká, E., Rampichová, M., East, B., Buzgo, M., Vysloužilová, L., Hoch, J., Amler, E.: (2015) Significant improvement of biocompatibility of polypropylene mesh for incisional hernia repair by using poly-ε-caprolactone nanofibers functionalized with thrombocyte-rich solution. Int J Nanomedicine.10:2635-2646.

Prosecká, E., Rampichová, M., Litvinec, A., Tonar, Z., Králíčková, M., Vojtová, L., Kochová, P., Plencner, M., Buzgo, M., Míčková, A., Jančář, J., Amler, E.: (2015) Collagen/hydroxyapatite scaffold enriched with polycaprolactone nanofibers, thrombocyte-rich solution and mesenchymal stem cells promotes regeneration in large bone defect in vivo. J. Biomed. Mater. Res. Part A., 103(2): 671-682.

Sukhoruková, I.V., Sheveyko, A.N., Kiryukhantsev-Korneev,Ph.V., AnisimováN.Y., Gloushanková, N.A., Zhitnyak, I.Y., Benešová, J., Amler, E., Shtanský, D.V.: (2015) Two approaches to form antibacterial surface: Doping with bactericidal element and drug loading. Applied Surface Science. 330:339–350.

2014

Amler, E., Filová, E., Buzgo, M., Prosecká, E., Rampichová, M., Nečas, A., Nooeaid, P., Boccaccini, A. R.: (2014) Functionalized nanofibers as drug-delivery systems for osteochondral regeneration. Nanomedicine-UK 9(7): 1083-1094.

Fedorová, P., Srnec, R., Pěnčík, J., Schmid, P., Amler, E., Urbanová, L., Nečas, A.: (2014) Mechanical testing of newly developed biomaterial designed for intra-articular reinforcement of partially ruptured cranial cruciate ligament: ex vivo pig model. Acta Vet.BRNO 83(1): 55-60.

Plencner, M., East, B., Tonar, Z., Otáhal, M., Prosecká, E., Rampichová, M., Krejčí, T., Litvinec, A., Buzgo, M., Míčková, A., Nečas, A., Hoch, J., Amler, E.: (2014) Abdominal closure reinforcement by using polypropylene mesh functionalized with poly-ε-caprolactone nanofibers and growth factors for prevention of incisional hernia formation. Int. J. Nanomed. 9: 3263-3277.

Rampichová, M., Buzgo, M., Chvojka, J., Prosecká, E., Kofroňová, O., Amler, E.: (2014) Cell penetration to nanofibrous scaffolds: Forcespinning®, an alternative approach for fabricating 3D nanofibers. Celll Adhes. Migr. 8(1): 36-41.

2013

Amler, E., Míčková, A., Buzgo, M.: (2013) Electrospun core/shell nanofibers: a promising system for cartilage and tissue engineering? Nanomedicine-UK. 8(4): 509-512.

Buzgo, M., Jakubová, R., Míčková, A., Rampichová, M., Prosecká, E., Kochová, P., Lukas, D., Amler, E.: (2013) Time-regulated drug delivery system based on coaxially incorporated platelet alpha granules for biomedical use. Nanomedicine-UK. 8(7): 1137-1154.

Filová, E., Rampichová M., Litvinec, A., Držík, M., Míčková, A., Buzgo, M., Košťáková, E., Martinová, L., Usvald, D., Prosecká, E., Uhlík, J., Motlík, J., Vajner, L., Amler, E.: (2013) A cell-free nanofiber composite scaffold regenerated osteochondral defects in miniature pigs. Int. J. Pharm. 447(1-2): 139-149.

Rampichová, M., Chvojka, J., Buzgo, M., Prosecká, E., Mikeš, P., Vysloužilová, L., Tvrdik, D., Kochová, P., Gregor, T., Lukáš, D.,Amler, E.: (2013) Elastic three-dimensional poly (ε-caprolactone) nanofibre scaffold enhanced migration, proliferation, and osteogenic differentiation of mesenchymal stem cells. Cell Prolif. 46(1): 23-37.

Czech Science Foundation 18-09306S (2018-2020) Development of advanced 3D in vitro of osteoporosis and investigation of the mechanism of biomaterials osteointegration for bone regeneration

Ministry of Industry and Trade of the Czech Republic, project FV30086 (2018-2021) Wound dressing with antioxidant and anti-bacterial function for chronic wounds healing.

Ministry of Industry and Trade of the Czech Republic, project FV40187 (2019-2022) New methods of preparing highly sophisticated wound dressings optimisation and validation for use primarily in healthcare

Ministry of Industry and Trade of the Czech Republic, FV40437 (2019-2022) Acti-TOX: Active 3D culture systems for advanced toxicological testing and reduction of animal testing

Ministry of Health of the Czech Republic NV18-05-00379 (2018-2021) Development and comprehensive evaluation of novel injectable, resorbable, porous bone substitute with controlled release of antimicrobial agents

European Commission, H2020-MSCA- RISE-2018, 8240072 (2019 – 2023) iP-OSTEO - Induced pluripotent stem cell seeded active osteochondral nanofibrous scaffolds

European Commission, H2020-MSCA-RISE-2018, 823981 (2019 - 2023) ActiTOX - Active organotypic models for nanoparticle toxicological screening

Technology Agency of the Czech Republic FW01010662 (2020 – 2024) Drug delivery systems for treatment of osteoporotic fractures

Aplikace CZ.01.1.02/0.0/0.0/17_107/0012524 (OPPIK, Czech Ministry of Industry and Trade): Development of products based on human bone extracellular matrix for applications in tissue engineering

University Centre for Energy Efficient Buildings, Czech Technical University in Prague

Faculty of Mechanical Engineering, Czech Technical University in Prague

Faculty of Chemical Technology, University of Chemistry and Technology in Prague

Brno University of Technology, Faculty of Chemistry, Institute of Materials Science

Faculty of Medicine in Plzen, Charles University

Biomedical Center of the Faculty of Medicine in Pilsen

CEITEC – Central European Institute of Technology, Advanced Polymers and Composites

Pavol Jozef Šafárik University in Košice, Faculty of Medicine, Institute of Medical Biophysics

Second University of Naples, Department of Experimental Medicine, Naples, Italy

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