Extracellular matrix (ECM) hydrogels, produced by tissue decellularization are natural injectable materials suitable for neural tissue repair. However, the rapid biodegradation of these materials may disrupt neural tissue reconstruction in vivo. The aim of this study was to improve the stability of the previously described ECM hydrogel derived from human umbilical cord using genipin and N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), crosslinking at concentration of 0.5-10 mM. The hydrogels, crosslinked by genipin (ECM/G) or EDC (ECM/D), were evaluated in vitro in terms of their mechanical properties, degradation stability and biocompatibility. ECM/G, unlike ECM/D, crosslinked hydrogels revealed improved rheological properties when compared to uncrosslinked ECM. Both ECM/G and ECM/D slowed down the gelation time and increased the resistance against in vitro enzymatic degradation, while genipin crosslinking was more effective than EDC. Crosslinkers concentration of 1 mM enhanced the in vitro bio-stability of both ECM/G and ECM/D without affecting mesenchymal stem cell proliferation, axonal sprouting or neural stem cell growth and differentiation. Moreover, when injected into cortical photochemical lesion, genipin allowed in situ gelation and improved the retention of ECM for up to 2 weeks without any adverse tissue response or enhanced inflammatory reaction. In summary, we demonstrated that genipin, rather than EDC, improved the bio-stability of injectable ECM hydrogel in biocompatible concentration, and that ECM/G has potential as a scaffold for neural tissue application.

• MeSH
• extracelulární matrix chemie   MeSH
• hydrogely chemie   MeSH
• iridoidy * MeSH
• karbodiimidy aplikace a dávkování   MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• proliferace buněk fyziologie   MeSH
• pupečník cytologie   MeSH
• regenerace nervu fyziologie   MeSH
• tkáňové inženýrství MeSH
• tkáňové podpůrné struktury chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-ethyl-3-(3-(diethylamino)propyl)carbodiimide MeSH Prohlížeč
• genipin MeSH Prohlížeč
• hydrogely MeSH
• iridoidy * MeSH
• karbodiimidy MeSH

Autologous and allogenic human pericardia used as biomaterials for cardiovascular surgery are traditionally crosslinked with glutaraldehyde. In this work, we have evaluated the resistivity to collagenase digestion and the cytotoxicity of human pericardium crosslinked with various concentrations of glutaraldehyde in comparison with pericardium crosslinked by genipin, nordihydroguaiaretic acid, tannic acid, and in comparison with unmodified pericardium. Crosslinking retained the wavy-like morphology of native pericardium visualized by second harmonic generation microscopy. The collagenase digestion products were analyzed using SDS-PAGE, capillary electrophoresis, and a hydroxyproline assay. Glutaraldehyde and genipin crosslinking protected the native pericardium efficiently against digestion with collagenase III. Only low protection was provided by the other crosslinking agents. The cytotoxicity of crosslinked pericardium was evaluated using xCELLigence by monitoring the viability of porcine valve interstitial cells cultured in eluates from crosslinked pericardium. The highest cell index, reflecting both the number and the shape of the monitored cells was observed in eluates from genipin. Crosslinking pericardium grafts with genipin therefore seems to be a promising alternative procedure to the traditional crosslinking with glutaraldehyde, because it provides similarly high protection against degradation with collagenase, without cytotoxic effects.

• MeSH
• biokompatibilní materiály MeSH
• glutaraldehyd MeSH
• iridoidy MeSH
• kyselina nordihydroguaiaretová MeSH
• lidé MeSH
• perikard chemie   MeSH
• reagencia zkříženě vázaná * MeSH
• taniny MeSH
• transplantáty chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• srovnávací studie MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• genipin MeSH Prohlížeč
• glutaraldehyd MeSH
• iridoidy MeSH
• kyselina nordihydroguaiaretová MeSH
• reagencia zkříženě vázaná * MeSH
• taniny MeSH

Decellularized human pericardium is under study as an allogenic material for cardiovascular applications. The effects of crosslinking on the mechanical properties of decellularized pericardium were determined with a uniaxial tensile test, and the effects of crosslinking on the collagen structure of decellularized pericardium were determined by multiphoton microscopy. The viability of human umbilical vein endothelial cells seeded on decellularized human pericardium and on pericardium strongly and weakly crosslinked with glutaraldehyde and with genipin was evaluated by means of an MTS assay. The viability of the cells, measured by their metabolic activity, decreased considerably when the pericardium was crosslinked with glutaraldehyde. Conversely, the cell viability increased when the pericardium was crosslinked with genipin. Coating both non-modified pericardium and crosslinked pericardium with a fibrin mesh or with a mesh containing attached heparin and/or fibronectin led to a significant increase in cell viability. The highest degree of viability was attained for samples that were weakly crosslinked with genipin and modified by means of a fibrin and fibronectin coating. The results indicate a method by which in vivo endothelialization of human cardiac allografts or xenografts could potentially be encouraged.

• MeSH
• alografty MeSH
• biokompatibilní materiály * chemie   MeSH
• biomechanika MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   metabolismus   MeSH
• fibrin MeSH
• fibronektiny MeSH
• glutaraldehyd MeSH
• heterografty MeSH
• iridoidy MeSH
• kolagen chemie   ultrastruktura   MeSH
• lidé MeSH
• mikroskopie fluorescenční multifotonová MeSH
• perikard chemie   transplantace   ultrastruktura   MeSH
• pevnost v tahu MeSH
• povrchová plasmonová rezonance MeSH
• reagencia zkříženě vázaná MeSH
• testování materiálů MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biokompatibilní materiály * MeSH
• fibrin MeSH
• fibronektiny MeSH
• genipin MeSH Prohlížeč
• glutaraldehyd MeSH
• iridoidy MeSH
• kolagen MeSH
• reagencia zkříženě vázaná MeSH

Biohydrogels, composed of naturally occurring biopolymers are typically preferred over their synthetic analogues in bioapplications thanks to their biocompatibility, bioactivity, mechanical or degradation properties. Shaping biohydrogels on the single-cell length scales (micrometers) is a key ability needed to create bioequivalent artificial cell/tissue constructs and cannot be achieved with current methods. This work introduces a method for photolithographic synthesis of arbitrarily shaped microgels composed purely of a biopolymer of choice. The biopolymer is mixed with a sacrificial photocrosslinkable polymer, and the mixture is photocrosslinked in a lithographic process, yielding anisotropic microgels with the biopolymer entrapped in the network. Subsequent ionic or covalent biopolymer crosslinking followed by template cleavage yields a microgel composed purely of a biopolymer with the 3D shape dictated by the photocrosslinking process. Method feasibility is demonstrated with two model polysaccharide biopolymers (alginate, chitosan) using suitable crosslinking methods. Next, alginate microgels were used as microtaggants on a pharmaceutical oral solid dose formulation to prevent its counterfeiting. Since the alginate is approved as an additive in the food and pharmaceutical industries, the presented tagging system can be implemented in practical use much easier than systems comprising synthetic polymers.

• MeSH
• algináty chemie   MeSH
• biopolymery chemie   MeSH
• dextrany chemie   MeSH
• fluorescence MeSH
• hydrogely chemie   MeSH
• iridoidy chemie   MeSH
• methakryláty chemie   MeSH
• mikrogely chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• algináty MeSH
• biopolymery MeSH
• dextran hydroxyethyl methacrylate MeSH Prohlížeč
• dextrany MeSH
• genipin MeSH Prohlížeč
• hydrogely MeSH
• iridoidy MeSH
• methakryláty MeSH
• mikrogely MeSH

Nanocomposite scaffolds which aimed to imitate a bone extracellular matrix were prepared for bone surgery applications. The scaffolds consisted of polylactide electrospun nano/sub-micron fibres, a natural collagen matrix supplemented with sodium hyaluronate and natural calcium phosphate nano-particles (bioapatite). The mechanical properties of the scaffolds were improved by means of three different cross-linking agents: N-(3-dimethylamino propyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in an ethanol solution (EDC/NHS/EtOH), EDC/NHS in a phosphate buffer saline solution (EDC/NHS/PBS) and genipin. The effect of the various cross-linking conditions on the pore size, structure and mechanical properties of the scaffolds were subsequently studied. In addition, the mass loss, the swelling ratio and the pH of the scaffolds were determined following their immersion in a cell culture medium. Furthermore, the metabolic activity of human mesenchymal stem cells (hMSCs) cultivated in scaffold infusions for 2 and 7 days was assessed. Finally, studies were conducted of cell adhesion, proliferation and penetration into the scaffolds. With regard to the structural stability of the tested scaffolds, it was determined that EDC/NHS/PBS and genipin formed the most effectively cross-linked materials. Moreover, it was discovered that the genipin cross-linked scaffold also provided the best conditions for hMSC cultivation. In addition, the infusions from all the scaffolds were found to be non-cytotoxic. Thus, the genipin and EDC/NHS/PBS cross-linked scaffolds can be considered to be promising biomaterials for further in vivo testing and bone surgery applications.

• MeSH
• analýza selhání vybavení MeSH
• biokompatibilní materiály chemická syntéza   MeSH
• buněčná adheze fyziologie   MeSH
• design vybavení MeSH
• kolagen chemie   MeSH
• kostní matrix chemie   MeSH
• kostní náhrady chemická syntéza   MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   fyziologie   MeSH
• nanokompozity chemie   ultrastruktura   MeSH
• proliferace buněk fyziologie   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• testování materiálů MeSH
• tkáňové podpůrné struktury * MeSH
• transplantace mezenchymálních kmenových buněk přístrojové vybavení   metody   MeSH
• velikost částic MeSH
• viabilita buněk fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• kolagen MeSH
• kostní náhrady MeSH
• reagencia zkříženě vázaná MeSH

The application of polymeric biomaterial scaffolds utilizing crosslinking strategy has become an effective approach in these days. In the present study, the development and characterization of collagen-chitosan hydrogel film has been reported on using dual crosslinking agent's, i.e., tannic acid and genipin simultaneously. Incorporation of genipin imparts a greenish-blue color to the polymeric film. The effect of dual crosslinking and their successful interaction within the matrix was evaluated by infrared analysis spectroscopy. The porosity of the film was examined using scanning electron microscopy (SEM). Results of TGA determine the intermediate thermal degradation. Further, the crosslinking phenomenon has found primary impact on the strength of the films. Enzymatic degradation for the films was performed with lysozyme and lipase. The cell adhesion and proliferation was also accomplished using mouse embryonic cell lines wherein the cells cultured on the dual crosslinked film. The thriving utilization of such dual crosslinked polymeric film finds their applications in ophthalmology especially as an implant for temporary injured cornea and skin tissue regeneration.

• Klíčová slova
• chitosan, collagen, dual crosslinking, polymeric biomaterial,
• Publikační typ
• časopisecké články MeSH

Infections of the musculoskeletal system present a serious problem with regard to the field of orthopedic and trauma medicine. The aim of the experiment described in this study was to develop a resorbable nanostructured composite layer with the controlled elution of antibiotics. The layer is composed of collagen, hydroxyapatite nanoparticles, and vancomycin hydrochloride (10 wt%). The stability of the collagen was enhanced by means of cross-linking. Four cross-linking agents were studied, namely an ethanol solution, a phosphate buffer solution of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, genipin, and nordihydroguaiaretic acid. High performance liquid chromatography was used so as to characterize the in vitro release rates of the vancomycin and its crystalline degradation antibiotically inactive products over a 21-day period. The maximum concentration of the released active form of vancomycin (approximately 265 mg/L) exceeded the minimum inhibitory concentration up to an order of 17 times without triggering the burst releasing effect. At the end of the experiment, the minimum inhibitory concentration was exceeded by up to 6 times (approximately 100 mg/L). It was determined that the modification of collagen with hydroxyapatite nanoparticles does not negatively influence the sustainable release of vancomycin. The balance of vancomycin and its degradation products was observed after 14 days of incubation.

• Klíčová slova
• HPLC, anti-infectives, coating, controlled release, degradation products, drug delivery systems, nanoparticles, pharmacokinetics, polymeric drug delivery systems,
• MeSH
• hydroxyapatit MeSH
• karbodiimidy chemie   MeSH
• kolagen chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• methylaminy chemie   MeSH
• nanočástice chemie   MeSH
• nanostruktury chemie   MeSH
• nosiče léků chemie   MeSH
• systémy cílené aplikace léků metody   MeSH
• vankomycin chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-(3-dimethylaminopropyl)-dimethylaminopropyl-ethylcarbodiimide hydrochloride MeSH Prohlížeč
• hydroxyapatit MeSH
• karbodiimidy MeSH
• kolagen MeSH
• léky s prodlouženým účinkem MeSH
• methylaminy MeSH
• nosiče léků MeSH
• vankomycin MeSH

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article.

• Klíčová slova
• Chitosan polymer, Composite hydrogels, Cross-linkers, Drug delivery, Hydrogels,
• MeSH
• aldehydy MeSH
• chitosan * MeSH
• epoxidové sloučeniny MeSH
• hydrogely MeSH
• kyseliny karboxylové MeSH
• polymery MeSH
• systémy cílené aplikace léků metody   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aldehydy MeSH
• chitosan * MeSH
• epoxidové sloučeniny MeSH
• hydrogely MeSH
• kyseliny karboxylové MeSH
• polymery MeSH