The department is focused on the development of artificial tissues and we also try to transfer newly developed technologies and know‑how into clinical practice. We are developing the technology of controlled drug delivery from nano/microfiber scaffolds with liposomes for the targeted release of drugs into the defect. We are developing artificial scaffolds for the regeneration of bone and cartilage in clinical practice. We are developing in vitro models of different tissues for toxicological screening of nanoparticals and chemical compounds and for the testing of the effects of antiosteoporotic drugs.
Optimizing printability and mechanical properties of poly(3-hydroxybutyrate) biocomposite blends and their biological response to Saos-2 cells
The study focuses on the development and optimization of materials designed for 3D printing of scaffolds for bone tissue engineering. The composite used was based on polyhydroxybutyrate (PHB) and further modified with polylactic acid (PLA), hydroxyapatite, a plasticizer, and polavinylalcohol (PVA) (prepared at Brno University of Technology, Institute of Material Chemistry). On 3D-printed scaffolds, we assessed metabolic activity, proliferation, and osteogenic differentiation of Saos-2 cells over a 21-day culture period. The most favorable cellular response was observed in blends with higher hydroxyapatite content and lower levels of plasticizer, which also promoted increased mineralization. Overall, the optimized PHB composites demonstrate strong potential for applications in bone regeneration.
3D printed poly(3-hydroxybutyrate)-based blends. The experimental scheme illustrates the preparation of various poly(3-hydroxybutyrate)-based (PH3B) blends used for filament fabrication and 3D printing of scaffolds for bone tissue engineering (A). The biological response of Saos-2 cells to selected materials (Mix 9–13) was evaluated in terms of cell proliferation (B) and osteogenic differentiation, assessed by alkaline phosphatase activity (C). Representative confocal microscopy images of cells growing on the Mix 13 scaffold after 14 days (upper image) and 21 days of culture (lower image) are shown in (D). Cell nuclei were stained with propidium iodide (red) and cell membranes with DiOC6(3) (green). Scale bar: 200 µm.
Publication:
Štěpán Krobot, Přemysl Menčík, Kateřina Chaloupková, Ján Bočkaj, Sára Vach Agócsová, Michala Klusáček Rampichová, Věra Hedvičáková, Pavol Alexy, Radek Přikryl, Veronika Melčová. Optimizing printability and mechanical properties of poly(3-hydroxybutyrate) biocomposite blends and their biological response to Saos-2 cells. International Journal of Bioprinting 2025, 11(1), 400–417. https://doi.org/10.36922/ijb.5175
Cooperation:
Ústav chemie materiálů, Fakulta Chemická, VUT Brno Brno, ČR;
Fakulta chemickej a potravinárskej technológie Slovenskej technickej univerzity v Bratislave, SR
Hybrid organosilane nanofibre scaffold formation supporting cell adhesion and growth
In this study, an organosilane nanofibrous (NFs) scaffold comprising of N,N’-bis(3-(triethoxysilyl)propyl) oxamide (BTPO) was electrospun. Prepared material showed good protein adsorption and cell proliferation and negligible cytotoxicity compared to poly(ε-caprolactone) and also tetraethoxysilane NFs materials. Therefore, BTPO NF is a promising scaffolding material for use in medicine. Moreover, the pure one-pot procedure ensures no complications arising from multicomponent materials.
Cell proliferation and distribution on nanofibrous materials detected by confocal microscopy. Cell nuclei were stained using propidium iodide (red colour), and intracellular membranes using DiOC6(3) (green colour) on days 1 and 7. Filamentous actin stained by phalloidin (red colour), and nuclei stained by Hoechst (blue colour) on day 14. Scale bars shown are 100 μm. Abbreviations: N,N´-bis(3-(triethoxysilyl)propyl)oxamide (BTPO), tetraethoxysilane (TEOS), polycaprolactone (PCL).
Publication:
Hobbs C., Kulhankova J., Holubová B., Mahun A., Kobera L., Erben J., Hedvicakova V., Hauzerova S., Rysova M., Makova V., Hybrid organosilane nanofibre scaffold formation supporting cell adhesion and growth, Journal of Materials Science. 2024; 59:19612–19627, https://doi.org/10.1007/s10853-024-10324-0
The gradual release of alendronate for the treatment of critical bone defects in osteoporotic and control rats
Osteoporosis is a widespread, serious disease whose standard treatment consists of the systematic administration of bisphosphonates, most commonly alendronate (ALN). However, systematic administration is associated with negative side effects. In this study, we developed a polycaprolactone/nanohydroxyapatite scaffold with encapsulated ALN, for local drug release directly at the site of bone damage. ALN was gradually released from the scaffold over 22 days. An in vivo study demonstrated the effect of the released ALN, which supported peri-implant bone formation.
Micro-CT of bone defects after 6-week regeneration. Micro-CT analysis of defects showed that denser bone formation occurred in the vicinity of ALN-containing scaffolds (PCL/HA/ALN) compared to the ALN-free scaffolds (PCL/HA) and the control empty defect (Empty), both in osteoporosis-induced (OP) and control animals (C). Results were not affected by systemic administration of ALN (+ALN) compared to animals without systemic treatment (-ALN)
Publication:
Hedvičáková, V., Žižková, R., Buzgo, M., Vištejnová, L., Klein, P., Hovořáková, M., Bartoš, M., Steklíková, K., Luňáčková, J., Šebová, E., Paurová, I., Rysová, M., Filová, E., & Rampichová, M. (2023). The Gradual Release of Alendronate for the Treatment of Critical Bone Defects in Osteoporotic and Control Rats. International journal of nanomedicine, 18, 541–560. https://doi.org/10.2147/IJN.S386784
The Effect of Osteoblast Isolation Methods from Adult Rats on Osteoclastogenesis in Co-Cultures
Cell co-cultures represent the future of in vitro studies important for testing of tissue substitutes and research of diseases. During the development of the co-culture of osteoblasts and osteoclasts, the influence of the osteoblast isolation method on the formation of osteoclasts was investigated. It was found that the explant culture isolation method induces the formation of a higher number of osteoclasts, with a larger area than the explant culture with enzymatic pre-treatment method.
Rat osteoclasts in a co-culture with osteoblasts isolated with different methods. Number, area, and number of nuclei of rat osteoclasts (rOCs) in a co-culture with osteoblasts isolated by explant culture with enzymatic pre-treatment or by explant culture.
Histochemical staining of co-culture of osteoclasts and osteoblasts isolated with different methods. Histochemical staining of co-culture of osteoclasts and osteoblasts isolated by explant culture with enzymatic pre-treatment or explant culture. White arrows indicate formed osteoclasts. Magnification 40×, scale bar 500 µm; 100×, scale bar 200 µm
Publication:
Žižková, R., Hedvičáková, V., Blahnová Hefka, V., Sovková, V., Rampichová, M., Filová, E.: (2022) The Effect of Osteoblast Isolation Methods from Adult Rats on Osteoclastogenesis in Co-Cultures. International Journal of Molecular Sciences. 23(14):7875.
Lumbar Interbody Fusion Conducted on a Porcine Model with a Bioresorbable Ceramic/Biopolymer Hybrid Implant Enriched with Hyperstable Fibroblast Growth Factor 2
Stabilized fibroblast growth factor-2 (FGF2-STAB®) exhibiting a functional half-life at 37 °C for more than 20 days was applied for lumbar fusion in combination with a bioresorbable scaffold on porcine models. The fusion quality of spines treated with scaffold involving inorganic hydroxyapatite and tricalcium phosphate along with organic collagen, oxidized cellulose, and FGF2- STAB® showed a significant increase in fusion quality in comparison to the autograft control group 16 weeks post-surgery.
In vitro verification of ceramic implants biocompatibility. In vitro verification of ceramic implants biocompatibility: hMSC proliferation was measured using dsDNA quantification (A). Statistical significance is shown by bars above the columns (p < 0.05). Visualization of cell adhesion and distribution on scaffolds using a confocal microscope. Biphasic calcium phosphate scaffold (BCP) on day 1 (B), bioresorbable hybrid implant (BHI) implant on day 1 (C), BCP implant on day 14 (D), BHI implant on day 14 (E). Cell nuclei were stained using propidium iodide (red color) and intracellular membranes using DiOC6(3) (green color), scale bar 200 µm. Abbreviations: hMSC, human mesenchymal stem cells; BCP, pure ceramic implant; BHI, ceramic implant with biopolymers and FGF2-STAB®.
Publication:
Krticka, M., Planka, L., Vojtová, L., Nekuda, V., Šťastný, P., Sedláček, R., Brinek, A., Kavková, M., Gopfert, E., Hedvičáková, V., Rampichová, M., Křen, L., Lišková, K.,Ira, D., Dorazilová, J., Suchý, T., Zikmund, T., Kaiser, J., Starý, D., Faldyna, M., Trunec, M.: (2021) Lumbar Interbody Fusion Conducted on a Porcine Model with a Bioresorbable Ceramic/Biopolymer Hybrid Implant Enriched with Hyperstable Fibroblast Growth Factor 2. Biomedicines. 9(7): 733. doi: 10.3390/biomedicines9070733. PMID: 34202232; PMCID: PMC8301420.
Projects
2024–2027
Personalized bone reconstruction with fast-osseointegrative and antibacterial titanium implants after osteosarcoma surgical resection
Prevention and treatment of the orthopedic infections with injectable resorbable bone substitute gradually releasing pathogen-specific antimicrobial compounds
Department of Tissue EngineeringUllrich M. M.Pulipaka B.Yin J.Hlinková J.Zhang F.Chan M. W.O'Brien F. J.Dervan A.Dziemidowicz K.
2025
Mol Pharm . 2025 Jun 2;22(6):2905-2916. doi: 10.1021/acs.molpharmaceut.4c01270. Epub 2025 May 16.
Department of Tissue EngineeringNeuhoferova E.Kindermann M.Buzgo M.Vocetková K.Panek D. Cigler P.Benson V.
2025
J Mater Chem B . 2025 Jan 15;13(3):1037-1051. doi: 10.1039/d4tb01547a.
Department of Tissue Engineering Leal F.Nirwan V.Goncalves A.M.Panitschewski N.Filová E.Fahmi A.Costa P.F.
2023
International Journal of Polymeric Materials and Polymeric Biomaterials. IN PRESS.
Department of Tissue EngineeringCanciani E.Gagliano N.Paino F.Amler E.Divín R.Denti L.Henin D.Fiorati A.Dellavia C.
2021
Frontiers in Materials. 8: 670010.