Eva Krumbholcová

Czech Academy of Sciences, Institute of Macromolecular Chemistry

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Jiřı́ Michálek

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Martin Přádný

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Jiří Hodan

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Martin Hrubý

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Taťána Fenclová

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Lucie Bačáková

Czech Academy of Sciences

Miroslava Kapcalová

Czech Academy of Sciences

Radka Hobzová

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Eva Syková

Institute of Neuroimmunology of the Slovak Academy of Sciences

Pavla Jendelová

Charles University

Cooperative Institutions

Czech Academy of Sciences

Charles University

Czech Academy of Sciences, Institute of Macromolecular Chemistry

Czech Academy of Sciences, Institute of Experimental Medicine

General University Hospital in Prague

Czech Academy of Sciences, Institute of Physiology

University of Chemistry and Technology, Prague

Institute of Clinical and Experimental Medicine

Czech Academy of Sciences, Institute of Physics

Czech Academy of Sciences, Nuclear Physics Institute

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The Synthesis and Characterization of the Poly[N-vinylpyrrolidone-co-ethylidene-bis-3-(N-vinyl-2-pyrrolidone)] Hydrogel Matrix for Drug Delivery to the Gastrointestinal Tract

Macromolecular Symposia (2016)

Jakub Hrib Jakub Širc Radka Hobzová Eva Krumbholcová Zák A

Hydrogels based on copolymers of N-vinylpyrrolidone and ethylidene-bis-3-(N-vinyl-2-pyrrolidone) (EBVP) were prepared as polymer matrices for controlled release of high loads of hydrophilic compounds into the gastrointestinal tract. EBVP was synthesized and used as a crosslinking agent for the N-vinylpyrrolidone monomer. The polymerization mixtures, containing 65–80 wt.% of the model pharmacologically active compound, were polymerized to create cylindrical formulations. The release experiments were carried out under conditions corresponding to the digestive tract. Various compositions of hydrogel matrices were tested to reveal the influence of the active compound content and the crosslinking ratio on the release kinetics. Processes such as hydrogel swelling, dissolution and formulation disintegration were evaluated. The results obtained show that the system offers many possibilities to control the drug release to meet various medicinal requirements.

N-Vinylpyrrolidone

10.1002/masy.201650042

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Citations (1)

Polyacrylonitrile‒Chitosan IPN composite scaffolds that closely mimic the human trabecular bone structure for tissue engineering

Materials Today Chemistry (2024)

Lucie Kománková Antonín Brož Helena Hlídková Jiří Hodan Eva Krumbholcová

Polyacrylonitrile

10.1016/j.mtchem.2024.102253

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Doubly Porous Thermally-Modified Polyacrylonitrile Scaffolds for Tissue Engineering Closely Mimicking Human Trabecular Bone Structure

Lucie Kománková Antonín Brož Helena Hlídková Jiří Hodan Eva Krumbholcová

In this study, we introduce a unique doubly porous three-dimensional scaffold designed to mimic the morphological characteristics of human trabecular bone tissue closely. The scaffolds were fabricated through the thermal modification (TM) of polyacrylonitrile, featuring imprinted pores of the appropriate size to facilitate the ingrowth and proliferation of human osteoblasts throughout the entire pore volume created by a primary porogen, sodium chloride. The resulting material exhibits a dual porous morphological structure, in which adjustable larger pores support cellular ingrowth into the scaffold, while smaller pores, created using succinonitrile as a secondary porogen, enhance the diffusion of oxygen and nutrients to the developing cells. To enhance the material's mechanical properties, we introduced a secondary interpenetrating network (IPN) based on chitosan. Two cross-linking agents were investigated: the widely utilized glutaraldehyde and its non-toxic alternative, genipin. Incorporating the secondary IPN led to a significant improvement in the mechanical characteristics of the scaffold. Our findings indicate that the developed material is non-cytotoxic, and its chemical composition and morphological structure actively promote the adhesion and proliferation of the human osteosarcoma cell line SAOS-2, underscoring the scaffold's potential for applications in bone tissue engineering.

Polyacrylonitrile

10.2139/ssrn.4836437

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Adjusting the Chemical and Physical Properties of Hydrogels Leads to Improved Stem Cell Survival and Tissue Ingrowth in Spinal Cord Injury Reconstruction: A Comparative Study of Four Methacrylate Hydrogels

Stem Cells and Development (2013)

Aleš Hejčl Jiří Růžička Miroslava Kapcalová Karolína Turnovcová Eva Krumbholcová

Currently, there is no effective strategy for the treatment of spinal cord injury (SCI). A suitable combination of modern hydrogel materials, modified to effectively bridge the lesion cavity, combined with appropriate stem cell therapy seems to be a promising approach to repair spinal cord damage. We demonstrate the synergic effect of porosity and surface modification of hydrogels on mesenchymal stem cell (MSC) adhesiveness in vitro and their in vivo survival in an experimental model of SCI. MSCs were seeded on four different hydrogels: hydroxypropylmethacrylate-RGD prepared by heterophase separation (HPMA-HS-RGD) and three other hydrogels polymerized in the presence of a solid porogen: HPMA-SP, HPMA-SP-RGD, and hydroxy ethyl methacrylate [2-(methacryloyloxy)ethyl] trimethylammonium chloride (HEMA-MOETACl). Their adhesion capability and cell survival were evaluated at 1, 7, and 14 days after the seeding of MSCs on the hydrogel scaffolds. The cell-polymer scaffolds were then implanted into hemisected rat spinal cord, and MSC survival in vivo and the ingrowth of endogenous tissue elements were evaluated 1 month after implantation. In vitro data demonstrated that HEMA-MOETACl and HPMA-SP-RGD hydrogels were superior in the number of cells attached. In vivo, the highest cell survival was found in the HEMA-MOETACl hydrogels; however, only a small ingrowth of blood vessels and axons was observed. Both HPMA-SP and HPMA-SP-RGD hydrogels showed better survival of MSCs compared with the HPMA-HS-RGD hydrogel. The RGD sequence attached to both types of HPMA hydrogels significantly influenced the number of blood vessels inside the implanted hydrogels. Further, the porous structure of HPMA-SP hydrogels promoted a statistically significant greater ingrowth of axons and less connective tissue elements into the implant. Our results demonstrate that the physical and chemical properties of the HPMA-SP-RGD hydrogel show the best combination for bridging a spinal cord lesion, while the HEMA-MOETACl hydrogel serves as the best carrier of MSCs.

10.1089/scd.2012.0616

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Citations (30)

Useful Synthetic Polymer of N-vinylpyrrolidone, Its Properties and Applications

Chemické listy (2024)

Jiřı́ Michálek Miroslava Dušková‐Smrčková Eva Krumbholcová Jiří Podešva

This contribution summarizes the present-state of knowledge on vinylpyrrolidone, its (co)polymers, crosslinked structures based on it, and offers a rich survey of various applications, with a special focus on (bio)medicine. A brief history of this material is also given. Methods of preparation and technical parameters of both vinylpyrrolidone monomer and its various polymers are described. Important data are presented in tables.

N-Vinylpyrrolidone

10.54779/chl20240650

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HPMA-RGD Hydrogels Seeded with Mesenchymal Stem Cells Improve Functional Outcome in Chronic Spinal Cord Injury

Stem Cells and Development (2010)

Aleš Hejčl Jiří Šedý Miroslava Kapcalová David Arboleda-Toro Takashi Amemori

Chronic spinal cord injury (SCI) is characterized by tissue loss and a stable functional deficit. While several experimental therapies have proven to be partly successful for the treatment of acute SCI, treatment of chronic SCI is still challenging. We studied whether we can bridge a chronic spinal cord lesion by implantation of our newly developed hydrogel based on 2-hydroxypropyl methacrylamide, either alone or seeded with mesenchymal stem cells (MSCs), and whether this treatment leads to functional improvement. A balloon-induced compression lesion was performed in adult 2-month-old male Wistar rats. Five weeks after injury, HPMA-RGD hydrogels [N-(2-hydroxypropyl)-methacrylamide with attached amino acid sequences—Arg-Gly-Asp] were implanted into the lesion, either with or without seeded MSCs. Animals with chronic SCI served as controls. The animals were behaviorally tested using the Basso–Beattie–Breshnahan (BBB) (motor) and plantar (sensory) tests once a week for 6 months. Behavioral analysis showed a statistically significant improvement in rats with combined treatment, hydrogel and MSCs, compared with the control group (P < 0.05). Although a tendency toward improvement was found in rats treated with hydrogel only, this was not significant. Subsequently, the animals were sacrificed 6 months after SCI, and the spinal cord lesions evaluated histologically. The combined therapy (hydrogel with MSCs) prevented tissue atrophy (P < 0.05), and the hydrogels were infiltrated with axons myelinated with Schwann cells. Blood vessels and astrocytes also grew inside the implant. MSCs were present in the hydrogels even 5 months after implantation. We conclude that 5 weeks after injury, HPMA-RGD hydrogels seeded with MSCs can successfully bridge a spinal cord cavity and provide a scaffold for tissue regeneration. This treatment leads to functional improvement even in chronic SCI.

Glial scar

10.1089/scd.2009.0378

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Citations (134)

Hydrogel Tissue Expanders for Stomatology. Part II. Poly(styrene-maleic anhydride) Hydrogels

Polymers (2019)

Jakub Hrib Eva Krumbholcová Miroslava Dušková‐Smrčková Radka Hobzová Jakub Širc

Self-inflating soft tissue expanders represent a valuable modality in reconstructive surgery. For this purpose, particularly synthetic hydrogels that increase their volume by swelling in aqueous environment are used. The current challenge in the field is to deliver a material with a suitable protracted swelling response, ideally with an induction period (for sutured wound healing) followed by a linear increase in volume lasting several days for required tissue reconstruction. Here, we report on synthesis, swelling, thermal, mechanical and biological properties of novel hydrogel tissue expanders based on poly(styrene-alt-maleic anhydride) copolymers covalently crosslinked with p-divinylbenzene. The hydrogels exerted hydrolysis-driven swelling response with induction period over the first two days with minimal volume change and gradual volume growth within 30 days in buffered saline solution. Their final swollen volume reached more than 14 times the dry volume with little dependence on the crosslinker content. The mechanical coherence of samples during swelling and in their fully swollen state was excellent, the compression modulus of elasticity being between 750 and 850 kPa. In vitro cell culture experiments and in vivo evaluation in mice models showed excellent biocompatibility and suitable swelling responses meeting thus the application requirements as soft tissue expanders.

Biocompatibility

Maleic anhydride

10.3390/polym11071087

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Citations (9)

Electrospinning of the hydrophilic poly (2-hydroxyethyl methacrylate) and its copolymers with 2-ethoxyethyl methacrylate

Open Chemistry (2007)

Martin Přádný Lenka Martinová Jiřı́ Michálek Taťána Fenclová Eva Krumbholcová

Abstract The goal was to electrospin 2-hydroxyethyl methacrylate — based biocompatible polymers and prepare submicron fibres (nanofibers) for biomedicinal applications. Syntheses of poly(2-hydroxyethyl methacrylate) (HEMA) and its copolymer with 2-ethoxyethyl methacrylate (EOEMA), and their characterization by viscometry and molecular weight are described. Their relation to electrospinning is discussed. Electrospinning of HEMA homopolymer from water-ethanol is successful for molecular weights 6.31 × 105 and 1.80 × 106 g/mol. Electrospinning of HEMA/EOEMA copolymers is feasible from ethanol.

2-Hydroxyethyl Methacrylate

Electrospinning

10.2478/s11532-007-0021-0

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Citations (12)

Cultivation of human keratinocytes without feeder cells on polymer carriers containing ethoxyethyl methacrylate: in vitro study

Journal of Materials Science Materials in Medicine (2007)

J. Vacı́k Barbora Dvořánková Jiřı́ Michálek Martin Přádný Eva Krumbholcová

10.1007/s10856-007-3225-0

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Citations (13)

Plasma modification of HEMA and EOEMA surface properties

Radiation effects and defects in solids (2006)

Václav Švorčı́k Kateřina Kolářová Barbora Dvořánková Jiřı́ Michálek Eva Krumbholcová

Abstract Process of plasma etching of poly(2-hydroxyethylmethacrylate) (HEMA) and poly(2-ethyloxyethyl methacrylate) (EOEMA) in Ar atmosphere at room temperature was studied. Ablation of the samples exposed to the plasma was determined by gravimetry, surface wettability by goniometry, chemical structure by FTIR spectroscopy and surface morphology by Scanning Electron (SEM) microscopy. Adhesion and proliferation of 3T3 mouse fibroblasts was studied in vitro in order to determine biological activity of plasma-modified HEMA and EOEMA substrates. It was demonstrated that the plasma etching leads to oxidation of HEMA and to an increase of its wettability. More estheric structures are produced in EOEMA. For both polymers, a surface layer ∼2 μm thick is ablated after plasma etching for 400 s. The etching changes the sample surface morphology and its biological activity. The surface becomes smoother after etching. The results obtained after 3T3 cells cultivation show that the plasma etching decreases cell adhesion and increases cell proliferation in comparison with pristine polymers. Keywords: PolymerHEMAEOEMAPlasma modificationSurface propertiesCell adhesion and proliferation Acknowledgements The work was supported by the Grant Agency of the CR under the project No. 106-03-0514 and by Grant Agency of the AS CR under the project A 5011301.

Plasma Etching

Surface Modification

Morphology

10.1080/10420150600554541

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Citations (3)