George Mihail Vlasceanu

@upb.ro

Faculty of Medical Engineering, Department of Bioengineering and Biotechnology
National University of Science and Technology POLITEHNICA Bucharest

https://researchid.co/george.vlasceanu

RESEARCH, TEACHING, or OTHER INTERESTS

Biomedical Engineering, Biomaterials, Bioengineering, Multidisciplinary

Scopus Publications

1139

Scholar Citations

Scholar h-index

Scholar i10-index

Scopus Publications

Advanced Nanobiocomposite Hydrogels Incorporating Organofunctionalized LDH for Soft Tissue Engineering Applications
Ionut-Cristian Radu, Eugenia Tanasa, Sorina Dinescu, George Vlasceanu, and Catalin Zaharia
MDPI AG
Nanocomposite hydrogels are gaining significant attention for biomedical applications in soft tissue engineering due to the increasing demand for highly flexible and durable soft polymer materials. This research paper focused on investigating and optimizing a procedure for the development of novel nanocomposite hydrogels based on poly(2-hydroxyethyl methacrylate)-co-(2-acrylamido-2-methylpropane sulfonic acid) (HEMA/AMPSA) copolymers. These hydrogels were synthesized through a grafting-through process, where the polymer network was formed using a modified clay crosslinker. The layered double hydroxide (LDH) clay modified with 3-(trimethoxysilyl)propyl methacrylate (ATPM) was synthesized using a novel recipe through a two-step procedure. The nanocomposite hydrogel compositions were optimized to achieve soft hydrogels with high flexibility. The developed materials were analyzed for their mechanical and morphological properties using tensile and compressive tests, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and micro-computed tomography (micro-CT). The swelling behavior, network density, and kinetic diffusion mechanism demonstrated the specific characteristics of the materials. The modified LDH-ATPM was further characterized using Thermogravimetry (TGA), FTIR-ATR and X-ray diffraction (XRD). Biological assessments on human adipose-derived stem cells (hASCs) were essential to evaluate the biocompatibility of the nanocomposite hydrogels and their potential for soft tissue applications.

Dual nanofiber and graphene reinforcement of 3D printed biomimetic supports for bone tissue repair
Elena Cojocaru, Mădălina Oprea, George Mihail Vlăsceanu, Mădălina-Cristina Nicolae, Roxana-Cristina Popescu, Paul-Emil Mereuţă, Alin-Georgian Toader, and Mariana Ioniţă
Royal Society of Chemistry (RSC)
Replicating the intricate architecture of the extracellular matrix by designing anisotropic biomimetic scaffolds with dual reinforcement of graphene oxide and electrospun nanofibers.

Fabrication of k-Carrageenan/Alginate/Carboxymethyl Cellulose basedScaffolds via 3D Printing for Potential Biomedical Applications
Cristina Stavarache, Adi Ghebaur, Andrada Serafim, George Mihail Vlăsceanu, Eugeniu Vasile, Sorina Alexandra Gârea, and Horia Iovu
MDPI AG
Three-dimensional (3D) printing technology was able to generate great attention because of its unique methodology and for its major potential to manufacture detailed and customizable scaffolds in terms of size, shape and pore structure in fields like medicine, pharmaceutics and food. This study aims to fabricate an ink entirely composed of natural polymers, alginate, k-carrageenan and carboxymethyl cellulose (AkCMC). Extrusion-based 3D printing was used to obtain scaffolds based on a crosslinked interpenetrating polymer network from the alginate, k-carrageenan, carboxymethyl cellulose and glutaraldehide formulation using CaCl2, KCl and glutaraldehyde in various concentrations of acetic acid. The stabile bonding of the crosslinked scaffolds was assessed using infrared spectroscopy (FT-IR) as well as swelling, degradation and mechanical investigations. Moreover, morphology analysis (µCT and SEM) confirmed the 3D printed samples’ porous structure. In the AkCMC-GA objects crosslinked with the biggest acetic acid concentration, the values of pores and walls are the highest, at 3.9 × 10−2 µm−1. Additionally, this research proves the encapsulation of vitamin B1 via FT-IR and UV-Vis spectroscopy. The highest encapsulation efficiency of vitamin B1 was registered for the AkCMC-GA samples crosslinked with the maximum acetic acid concentration. The kinetic release of the vitamin was evaluated by UV-Vis spectroscopy. Based on the results of these experiments, 3D printed constructs using AkCMC-GA ink could be used for soft tissue engineering applications and also for vitamin B1 encapsulation.

Three-Dimensional-Printed Sodium Alginate and k-Carrageenan-Based Scaffolds with Potential Biomedical Applications
Cristina Stavarache, Sorina Alexandra Gȃrea, Andrada Serafim, Elena Olăreț, George Mihail Vlăsceanu, Maria Minodora Marin, and Horia Iovu
MDPI AG
This work reports the development of a marine-derived polysaccharide formulation based on k-Carrageenan and sodium alginate in order to produce a novel scaffold for engineering applications. The viscoelastic properties of the bicomponent inks were assessed via rheological tests prior to 3D printing. Compositions with different weight ratios between the two polymers, without any crosslinker, were subjected to 3D printing for the first time, to the best of our knowledge, and the fabrication parameters were optimized to ensure a controlled architecture. Crosslinking of the 3D-printed scaffolds was performed in the presence of a chloride mixture (CaCl2:KCl = 1:1; v/v) of different concentrations. The efficiency of the crosslinking protocol was evaluated in terms of swelling behavior and mechanical properties. The swelling behavior indicated a decrease in the swelling degree when the concentration of the crosslinking agent was increased. These results are consistent with the nanoindentation measurements and the results of the macro-scale tests. Moreover, morphology analysis was also used to determine the pore size of the samples upon freeze-drying and the uniformity and micro-architectural characteristics of the scaffolds. Overall, the registered results indicated that the bicomponent ink, Alg/kCG = 1:1 may exhibit potential for tissue-engineering applications.

Advances in Therapeutic Contact Lenses for the Management of Different Ocular Conditions
Mariana Ioniță, George Mihail Vlăsceanu, Alin Georgian Toader, and Marius Manole
MDPI AG
In the advent of an increasingly aging population and due to the popularity of electronic devices, ocular conditions have become more prevalent. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many commercial eye drops, most of them have important limitations, due to quick clearance mechanisms and ocular barrers. One solution with tremendous potential is the contact lens used as a medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability and patient compliance, both with minimal side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus to attain positive in vitro and in vivo outcomes with respect to a sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physico-chemical features caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials, to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses polymeric materials, and a specialized molecule-recognition technique called molecular imprinting or a stimuli–responsive system to improve biocompatibility and support the drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices of ophthalmic therapies and projects an outlook onto future opportunities in the field of eye condition management by means of an active principle-eluting contact lens.

Human Bone-Marrow-Derived Stem-Cell-Seeded 3D Chitosan–Gelatin–Genipin Scaffolds Show Enhanced Extracellular Matrix Mineralization When Cultured under a Perfusion Flow in Osteogenic Medium
Gabriele Boretti, Emanuele Giordano, Mariana Ionita, George Mihail Vlasceanu, Ólafur Eysteinn Sigurjónsson, Paolo Gargiulo, and Joseph Lovecchio
MDPI AG
Tissue-engineered bone tissue grafts are a promising alternative to the more conventional use of natural donor bone grafts. However, choosing an appropriate biomaterial/scaffold to sustain cell survival, proliferation, and differentiation in a 3D environment remains one of the most critical issues in this domain. Recently, chitosan/gelatin/genipin (CGG) hybrid scaffolds have been proven as a more suitable environment to induce osteogenic commitment in undifferentiated cells when doped with graphene oxide (GO). Some concern is, however, raised towards the use of graphene and graphene-related material in medical applications. The purpose of this work was thus to check if the osteogenic potential of CGG scaffolds without added GO could be increased by improving the medium diffusion in a 3D culture of differentiating cells. To this aim, the level of extracellular matrix (ECM) mineralization was evaluated in human bone-marrow-derived stem cell (hBMSC)-seeded 3D CGG scaffolds upon culture under a perfusion flow in a dedicated custom-made bioreactor system. One week after initiating dynamic culture, histological/histochemical evaluations of CGG scaffolds were carried out to analyze the early osteogenic commitment of the culture. The analyses show the enhanced ECM mineralization of the 3D perfused culture compared to the static counterpart. The results of this investigation reveal a new perspective on more efficient clinical applications of CGG scaffolds without added GO.

3D double-reinforced graphene oxide - nanocellulose biomaterial inks for tissue engineered constructs
Alexandra I. Cernencu, George M. Vlasceanu, Andrada Serafim, Gratiela Pircalabioru, and Mariana Ionita
Royal Society of Chemistry (RSC)
The advent of 3D printing technology has enabled the engineering of bone tissue for patient-specific healing and the fabrication of in vitro tissue models for ex vivo testing.

Nanocellulose Sponges Containing Antibacterial Basil Extract
Gabriela Mădălina Oprică, Denis Mihaela Panaitescu, Catalina Diana Usurelu, George Mihai Vlăsceanu, Paul Octavian Stanescu, Brandusa Elena Lixandru, Valentin Vasile, Augusta Raluca Gabor, Cristian-Andi Nicolae, Marius Ghiurea,et al.
MDPI AG
Nanocellulose (NC) is a valuable material in tissue engineering, wound dressing, and drug delivery, but its lack of antimicrobial activity is a major drawback for these applications. In this work, basil ethanolic extract (BE) and basil seed mucilage (BSM) were used to endow nanocellulose with antibacterial activity. NC/BE and NC/BE/BSM sponges were obtained from nanocellulose suspensions and different amounts of BE and BSM after freeze-drying. Regardless of the BE or BSM content, the sponges started to decompose at a lower temperature due to the presence of highly volatile active compounds in BE. A SEM investigation revealed an opened-cell structure and nanofibrillar morphology for all the sponges, while highly impregnated nanofibers were observed by SEM in NC/BE sponges with higher amounts of BE. A quantitative evaluation of the porous morphology by microcomputer tomography showed that the open porosity of the sponges varied between 70% and 82%, being lower in the sponges with higher BE/BSM content due to the impregnation of cellulose nanofibers with BE/BSM, which led to smaller pores. The addition of BE increased the specific compression strength of the NC/BE sponges, with a higher amount of BE having a stronger effect. A slight inhibition of S. aureus growth was observed in the NC/BE sponges with a higher amount of BE, and no effect was observed in the unmodified NC. In addition, the NC/BE sponge with the highest amount of BE and the best antibacterial effect in the series showed no cytotoxic effect and did not interfere with the normal development of the L929 cell line, similar to the unmodified NC. This work uses a simple, straightforward method to obtain highly porous nanocellulose structures containing antibacterial basil extract for use in biomedical applications.

Double-Reinforced Fish Gelatin Composite Scaffolds for Osteochondral Substitutes
Alin Georgian Toader, George Mihail Vlasceanu, Andrada Serafim, Adela Banciu, and Mariana Ionita
MDPI AG
Genipin crosslinked composite blends of fish gelatin/kappa-carrageenan (fG/κC) with different concentrations of graphene oxide (GO) for osteochondral substitutes were prepared by a simple solution-blending method. The resulting structures were examined by micro-computer tomography, swelling studies, enzymatic degradations, compressions tests, MTT, LDH, and LIVE/DEAD assays. The derived findings revealed that genipin crosslinked fG/κC blends reinforced with GO have a homogenous morphology with ideal pore dimensions of 200–500 µm for bones alternative. GO additivation with a concentration above 1.25% increased the blends’ fluid absorption. The full degradation of the blends occurs in 10 days and the gel fraction stability increases with GO concentration. The blend compression modules decrease at first until fG/κC GO3, which has the least elastic behavior, then by raising the GO concentration the blends start to regain elasticity. The MC3T3-E1 cell viability reveals less viable cells with the increase of GO concentration. The LDH together with the LIVE/DEAD assays reports a high concentration of live and healthy cells in all types of composite blends and very few dead cells at the higher GO content.

Nanoclay-reinforced alginate/salecan composite inks for 3D printing applications
Raluca Ianchis, Maria Minodora Marin, Rebeca Leu Alexa, Ioana Catalina Gifu, Elvira Alexandrescu, Gratiela Gradisteanu Pircalabioru, George Mihail Vlasceanu, George Mihail Teodorescu, Andrada Serafim, Silviu Preda,et al.
AccScience Publishing
The main objective of the present work was to produce three-dimensional (3D)- printable nanocomposite hydrogels based on two kinds of marine-sourced polysaccharides doped with nanoclay with potential biomedical application. First part of the research study investigated the preparation of the polysaccharide bicomponent hydrogel formulations followed by the selection of the optimal ratio of polysaccharides concentrations which ensured proper morphostructural stability of the 3D-printed constructs. Second step aimed to generate 3D scaffolds with high printing fidelity by modulating the nanoclay amount doped within the previously selected biopolymer ink. In compliance with the additive manufacturing experiments, the alginate&ndash;salecan hydrogels enriched with the highest nanofiller concentrations demonstrated the highest suitability for 3D printing process. The morphological and structural studies confirmed the ability of the nanocomposite formulations to efficiently produce porous 3D-printed constructs with improved fidelity. The morphostructural findings underlined the implication of choosing the appropriate ratio between components, as they have a considerable impact on the functionality of printing formulations and subsequent 3D-printed structures. Hence, from the obtained results, these novel hydrogel nanocomposites inks are considered valuable biomaterials with suitable features for applications in the additive manufacturing of 3D structures with precise shape for customized regenerative therapy. &nbsp;

Nanofibrous scaffolds based on bacterial cellulose crosslinked with oxidized sucrose
Denis Mihaela Panaitescu, Sergiu Stoian, Adriana Nicoleta Frone, George Mihai Vlăsceanu, Dora Domnica Baciu, Augusta Raluca Gabor, Cristian Andi Nicolae, Valentin Radiţoiu, Elvira Alexandrescu, Angela Căşărică,et al.
Elsevier BV

3D Printed Composite Scaffolds of GelMA and Hydroxyapatite Nanopowders Doped with Mg/Zn Ions to Evaluate the Expression of Genes and Proteins of Osteogenic Markers
Rebeca Leu Alexa, Andreia Cucuruz, Cristina-Daniela Ghițulică, Georgeta Voicu, Liliana-Roxana Stamat (Balahura), Sorina Dinescu, George Mihail Vlasceanu, Horia Iovu, Andrada Serafim, Raluca Ianchis,et al.
MDPI AG
As bone diseases and defects are constantly increasing, the improvement of bone regeneration techniques is constantly evolving. The main purpose of this scientific study was to obtain and investigate biomaterials that can be used in tissue engineering. In this respect, nanocomposite inks of GelMA modified with hydroxyapatite (HA) substituted with Mg and Zn were developed. Using a 3D bioprinting technique, scaffolds with varying shapes and dimensions were obtained. The following analyses were used in order to study the nanocomposite materials and scaffolds obtained by the 3D printing technique: Fourier transform infrared spectrometry and X-ray diffraction (XRD), scanning electron microscopy (SEM), and micro-computed tomography (Micro-CT). The swelling and dissolvability of each scaffold were also studied. Biological studies, osteopontin (OPN), and osterix (OSX) gene expression evaluations were confirmed at the protein levels, using immunofluorescence coupled with confocal microscopy. These findings suggest the positive effect of magnesium and zinc on the osteogenic differentiation process. OSX fluorescent staining also confirmed the capacity of GelMA-HM5 and GelMA-HZ5 to support osteogenesis, especially of the magnesium enriched scaffold.

Chitosan-Based Materials Featuring Multiscale Anisotropy for Wider Tissue Engineering Applications
George Mihail Vlăsceanu, Mariana Ioniță, Corina Cristiana Popescu, Elena Diana Giol, Irina Ionescu, Andrei-Mihai Dumitrașcu, Mădălina Floarea, Iulian Boerasu, Mădălina Ioana Necolau, Elena Olăreț,et al.
MDPI AG
We designed graphene oxide composites with increased morphological and structural variability using fatty acid-coupled polysaccharide co-polymer as the continuous phase. The matrix was synthesized by N, O-acylation of chitosan with palmitic and lauric acid. The obtained co-polymer was crosslinked with genipin and composited with graphene oxide. FTIR spectra highlighted the modification and multi-components interaction. DLS, SEM, and contact angle tests demonstrated that the conjugation of hydrophobic molecules to chitosan increased surface roughness and hydrophilicity, since it triggered a core-shell macromolecular structuration. Nanoindentation revealed a notable durotaxis gradient due to chitosan/fatty acid self-organization and graphene sheet embedment. The composited building blocks with graphene oxide were more stable during in vitro enzymatic degradation tests and swelled less. In vitro viability, cytotoxicity, and inflammatory response tests yielded promising results, and the protein adsorption test demonstrated potential antifouling efficacy. The robust and stable substrates with heterogeneous architecture we developed show promise in biomedical applications.

3D Printable Composite Biomaterials Based on GelMA and Hydroxyapatite Powders Doped with Cerium Ions for Bone Tissue Regeneration
Rebeca Leu Alexa, Andreia Cucuruz, Cristina-Daniela Ghițulică, Georgeta Voicu, Liliana-Roxana Stamat (Balahura), Sorina Dinescu, George Mihail Vlasceanu, Cristina Stavarache, Raluca Ianchis, Horia Iovu,et al.
MDPI AG
The main objective was to produce 3D printable hydrogels based on GelMA and hydroxyapatite doped with cerium ions with potential application in bone regeneration. The first part of the study regards the substitution of Ca2+ ions from hydroxyapatite structure with cerium ions (Ca10-xCex(PO4)6(OH)2, xCe = 0.1, 0.3, 0.5). The second part followed the selection of the optimal concentration of HAp doped, which will ensure GelMA-based scaffolds with good biocompatibility, viability and cell proliferation. The third part aimed to select the optimal concentrations of GelMA for the 3D printing process (20%, 30% and 35%). In vitro biological assessment presented the highest level of cell viability and proliferation potency of GelMA-HC5 composites, along with a low cytotoxic potential, highlighting the beneficial effects of cerium on cell growth, also supported by Live/Dead results. According to the 3D printing experiments, the 30% GelMA enriched with HC5 was able to generate 3D scaffolds with high structural integrity and homogeneity, showing the highest suitability for the 3D printing process. The osteogenic differentiation experiments confirmed the ability of 30% GelMA-3% HC5 scaffold to support and efficiently maintain the osteogenesis process. Based on the results, 30% GelMA-3% HC5 3D printed scaffolds could be considered as biomaterials with suitable characteristics for application in bone tissue engineering.

Graphene–oxide porous biopolymer hybrids enhance in vitro osteogenic differentiation and promote ectopic osteogenesis in vivo
Aida Șelaru, Hildegard Herman, George Mihail Vlăsceanu, Sorina Dinescu, Sami Gharbia, Cornel Baltă, Marcel Roșu, Ciprian V. Mihali, Mariana Ioniță, Andrada Serafim,et al.
MDPI AG
Over the years, natural-based scaffolds have presented impressive results for bone tissue engineering (BTE) application. Further, outstanding interactions have been observed during the interaction of graphene oxide (GO)-reinforced biomaterials with both specific cell cultures and injured bone during in vivo experimental conditions. This research hereby addresses the potential of fish gelatin/chitosan (GCs) hybrids reinforced with GO to support in vitro osteogenic differentiation and, further, to investigate its behavior when implanted ectopically. Standard GCs formulation was referenced against genipin (Gp) crosslinked blend and 0.5 wt.% additivated GO composite (GCsGp/GO 0.5 wt.%). Pre-osteoblasts were put in contact with these composites and induced to differentiate in vitro towards mature osteoblasts for 28 days. Specific bone makers were investigated by qPCR and immunolabeling. Next, CD1 mice models were used to assess de novo osteogenic potential by ectopic implantation in the subcutaneous dorsum pocket of the animals. After 4 weeks, alkaline phosphate (ALP) and calcium deposits together with collagen synthesis were investigated by biochemical analysis and histology, respectively. Further, ex vivo materials were studied after surgery regarding biomineralization and morphological changes by means of qualitative and quantitative methods. Furthermore, X-ray diffraction and Fourier-transform infrared spectroscopy underlined the newly fashioned material structuration by virtue of mineralized extracellular matrix. Specific bone markers determination stressed the osteogenic phenotype of the cells populating the material in vitro and successfully differentiated towards mature bone cells. In vivo results of specific histological staining assays highlighted collagen formation and calcium deposits, which were further validated by micro-CT. It was observed that the addition of 0.5 wt.% GO had an overall significant positive effect on both in vitro differentiation and in vivo bone cell recruitment in the subcutaneous region. These data support the GO bioactivity in osteogenesis mechanisms as being self-sufficient to elevate osteoblast differentiation and bone formation in ectopic sites while lacking the most common osteoinductive agents.

Layered clay–graphene oxide nanohybrids for the reinforcement and fire-retardant properties of polyurea matrix
Mădălina Ioana Necolau, Celina Maria Damian, Radu Claudiu Fierăscu, Anita-Laura Chiriac, George Mihail Vlăsceanu, Eugeniu Vasile, and Horia Iovu
MDPI AG
Nanostructures are more and more evolved through extensive research on their functionalities; thus, the aim of this study was to obtain layered clay–graphene oxide nanohybrids with application as reinforcing agents in polyurea nanocomposites with enhanced thermal–mechanical and fire-retardant properties. Montmorillonite (MMT) was combined with graphene oxide (GO) and amine functionalized graphene oxide (GOD) through a new cation exchange method; the complex nanostructures were analyzed through FTIR and XPS to assess ionic interactions between clay layers and GO sheets by C1s deconvolution and specific C sp3, respective/ly, C-O secondary peaks appearance. The thermal decomposition of nanohybrids showed a great influence of MMT layers in TGA, while the XRD patterns highlighted mutual MMT and GO sheets crystalline-structure disruption by the d (002) shift 2θ = 6.29° to lower values. Furthermore, the nanohybrids were embedded in the polyurea matrix, and the thermo-mechanical analysis gave information about the stiffness of MMT–GO nanocomposites, while GOD insertion within the MMT layers resulted in a 30 °C improvement in the Tg of hard domains, as shown in the DSC study. The micro CT analysis show good dispersion of inorganic structures within the polyurea, while the SEM fracture images revealed smooth surfaces. Cone calorimetry was used to evaluate fire-retardant properties through limiting the oxygen index, and MMT–GOD based nanocomposites showed a 35.4% value.

3D printing of alginate-natural clay hydrogel-based nanocomposites
Rebeca Leu Alexa, Raluca Ianchis, Diana Savu, Mihaela Temelie, Bogdan Trica, Andrada Serafim, George Mihail Vlasceanu, Elvira Alexandrescu, Silviu Preda, and Horia Iovu
MDPI AG
Biocompatibility, biodegradability, shear tinning behavior, quick gelation and an easy crosslinking process makes alginate one of the most studied polysaccharides in the field of regenerative medicine. The main purpose of this study was to obtain tissue-like materials suitable for use in bone regeneration. In this respect, alginate and several types of clay were investigated as components of 3D-printing, nanocomposite inks. Using the extrusion-based nozzle, the nanocomposites inks were printed to obtain 3D multilayered scaffolds. To observe the behavior induced by each type of clay on alginate-based inks, rheology studies were performed on composite inks. The structure of the nanocomposites samples was examined using Fourier Transform Infrared Spectrometry and X-ray Diffraction (XRD), while the morphology of the 3D-printed scaffolds was evaluated using Electron Microscopy (SEM, TEM) and Micro-Computed Tomography (Micro-CT). The swelling and dissolvability of each composite scaffold in phosfate buffer solution were followed as function of time. Biological studies indicated that the cells grew in the presence of the alginate sample containing unmodified clay, and were able to proliferate and generate calcium deposits in MG-63 cells in the absence of specific signaling molecules. This study provides novel information on potential manufacturing methods for obtaining nanocomposite hydrogels suitable for 3D printing processes, as well as valuable information on the clay type selection for enabling accurate 3D-printed constructs. Moreover, this study constitutes the first comprehensive report related to the screening of several natural clays for the additive manufacturing of 3D constructs designed for bone reconstruction therapy.

Cellulose nanofiber-based hydrogels embedding 5-FU promote pyroptosis activation in breast cancer cells and support human adipose-derived stem cell proliferation, opening new perspectives for breast tissue engineering
Liliana-Roxana Balahura, Sorina Dinescu, Mihaela Balaș, Alexandra Cernencu, Adriana Lungu, George Mihail Vlăsceanu, Horia Iovu, and Marieta Costache
MDPI AG
The structure and biocompatibility analysis of a hydrogel based on cellulose nanofibers (CNFs) combined with alginate/pectin (A.CNF or P.CNF) and enriched with 1% or 5% 5-FU revealed more favorable properties for the cellular component when pectin was dispersed within CNFs. 5-Fluorouracil (5-FU) is an antimetabolite fluoropyrimidine used as antineoplastic drug for the treatment of multiple solid tumors. 5-FU activity leads to caspase-1 activation, secretion and maturation of interleukins (IL)-1, IL-18 and reactive oxygen species (ROS) generation. Furthermore, the effects of embedding 5-FU in P.CNF were explored in order to suppress breast tumor cell growth and induce inflammasome complex activation together with extra- and intracellular ROS generation. Exposure of tumor cells to P.CNF/5-FU resulted in a strong cytotoxic effect, an increased level of caspase-1 released in the culture media and ROS production—the latter directly proportional to the concentration of anti-tumor agent embedded in the scaffolds. Simultaneously, 5-FU determined the increase of p53 and caspase-1 expressions, both at gene and protein levels. In conclusion, P.CNF/5-FU scaffolds proved to be efficient against breast tumor cells growth due to pyroptosis induction. Furthermore, biocompatibility and the potential to support human adipose-derived stem cell growth were demonstrated, suggesting that these 3D systems could be used in soft tissue reconstruction post-mastectomy.

5-aminosalicylic acid loaded chitosan-carrageenan hydrogel beads with potential application for the treatment of inflammatory bowel disease
Cristina Elena Stavarache, Adi Ghebaur, Sorina Dinescu, Iuliana Samoilă, Eugeniu Vasile, George Mihail Vlasceanu, Horia Iovu, and Sorina Alexandra Gârea
MDPI AG
The aim of our work is to prepare mucoadhesive particles with biopolymers and 5-Aminosalicylic acid (5ASA) using the ionotropic gelation technique to ensure a controlled drug release at the colon level with potential applications in the treatment of intestinal bowel disease (IBD). The preparation of particles through the crosslinking of Chitosan (CS) with sodium tripolyphosphate (TPP) using different mass ratios and the influence of the k-Carrageenan (kCG) layer were studied. UV–VIS spectrometry was employed to assess encapsulation efficiency and drug release profile of 5ASA. The particles were investigated using FT-IR spectrometry for chemical characterization and the DLS results highlighted a monodisperse particle size distribution. The morphology of the polymeric beads was investigated using micro-computer tomography (µCT) and Scanning Electron Microscopy (SEM). Particles based on Chitosan and k-Carrageenan were able to incorporate and preserve 5ASA in an acidic and alkaline medium. The 5ASA loaded polymeric particles obtained after immersion for 1 h in kCG solution exhibited the lowest release rate in pH = 1.2. Biocompatibility studies performed on all of the particles displayed a good viability for the CCD 841 CoN cells and low cytotoxicity. All of the results have shown that these new biomaterials could be a versatile platform of targeted carriers with potential applications in inflammatory bowel disease treatment.

Assessment of naturally sourced mineral clays for the 3d printing of biopolymer-based nanocomposite inks
Rebeca Leu Alexa, Horia Iovu, Bogdan Trica, Catalin Zaharia, Andrada Serafim, Elvira Alexandrescu, Ionut-Cristian Radu, George Vlasceanu, Silviu Preda, Claudia Mihaela Ninciuleanu,et al.
MDPI AG
The present study investigated the possibility of obtaining 3D printed composite constructs using biomaterial-based nanocomposite inks. The biopolymeric matrix consisted of methacrylated gelatin (GelMA). Several types of nanoclay were added as the inorganic component. Our aim was to investigate the influence of clay type on the rheological behavior of ink formulations and to determine the morphological and structural properties of the resulting crosslinked hydrogel-based nanomaterials. Moreover, through the inclusion of nanoclays, our goal was to improve the printability and shape fidelity of nanocomposite scaffolds. The viscosity of all ink formulations was greater in the presence of inorganic nanoparticles as shear thinning occurred with increased shear rate. Hydrogel nanocomposites presented predominantly elastic rather than viscous behavior as the materials were crosslinked which led to improved mechanical properties. The inclusion of nanoclays in the biopolymeric matrix limited hydrogel swelling due the physical barrier effect but also because of the supplementary crosslinks induced by the clay layers. The distribution of inorganic filler within the GelMA-based hydrogels led to higher porosities as a consequence of their interaction with the biopolymeric ink. The present study could be useful for the development of soft nanomaterials foreseen for the additive manufacturing of customized implants for tissue engineering.

3D POSS cages decorated 2D graphenic sheets: A versatile platform for silicon-carbonaceous nano-additives design
A. Lungu, A.I. Cernencu, G.M. Vlasceanu, N.M. Florea, M. Ionita, and H. Iovu
Elsevier BV

The effect of crosslinking agents on the properties of type II collagen biomaterials
Maria-Minodora Marin, Madalina Georgiana Albu Kaya, George Mihail Vlasceanu, Jana Ghitman, Ionut Cristian Radu, and Horia Iovu
Revista de Chimie SRL
Type II collagen has been perceived as the indispensable element and plays a crucial role in cartilage tissue engineering. Thus, materials based on type II collagen have drawn farther attention in both academic and research for developing new systems for the cartilage regeneration. The disadvantage of using type II collagen as a biomaterial for tissue repairing is its reduced biomechanical properties. This can be solved by physical, enzymatic or chemical cross-linking processes, which provide biomaterials with the required mechanical properties for medical applications. To enhance type II collagen properties, crosslinked collagen scaffolds with different cross-linking agents were prepared by freeze-drying technique. The present research work studied the synthesis of type II collagen biomaterials with and without crosslinking agents. Scaffolds morphology was observed by MicroCT, showing in all cases an appropriate microstructure for biological applications, and the mechanical studies were performed using compressive tests. DSC showed an increase in denaturation temperature with an increase in cross-linking agent concentration. FTIR suggested that the secondary structure of collagen is not affected after the cross-linking; supplementary, to confirm the characteristic triple-helix conformation of collagen, the CD investigation was performed. The results showed that the physical-chemical properties of type II collagen were improved by cross-linking treatments.

Physico-chemical enhancements of natural biopolymer matrices by reinforcing with complex carbonaceous-oxidic fillers

Comprehensive appraisal of graphene–oxide ratio in porous biopolymer hybrids targeting bone-tissue regeneration
George Mihail Vlasceanu, Aida Șelaru, Sorina Dinescu, Cornel Balta, Hildegard Herman, Sami Gharbia, Anca Hermenean, Mariana Ionita, and Marieta Costache
MDPI AG
The bone-tissue engineering (BTE) field is continuously growing due to a major need for bone substitutes in cases of serious traumas, when the bone tissue has reduced capacity for self-regeneration. So far, graphene oxide (GO)-reinforced natural materials provide satisfactory results for BTE, for both in vitro and in vivo conditions. In this study, we aimed to evaluate the biocompatibility of a new biocomposite consisting of chitosan and fish gelatin crosslinked with genipin and loaded with various concentrations of GO (0.5, 1, 2, 3 wt.%) for prospective BTE applications. Scaffold characterizations revealed a constant swelling degree and good resistance to enzyme degradation. The composites presented a porous structure with pores of similar size, thus mimicking the bone structure. In vitro biocompatibility assays demonstrated an overall beneficial interaction between preosteoblasts, and these particular composites, particularly with 0.5 wt.% GO, reinforced composition. Next, the materials were implanted subcutaneously in 6-week old CD1 mice for in vivo evaluation of biocompatibility and inflammatory activity. Immunohistochemical staining revealed maximal cell infiltration and minimal inflammatory reaction for fish gelatin/chitosan/genipin with 0.5 wt.% GO scaffold, thus demonstrating the best biocompatibility for this particular composition, confirming the in vitro results. This study revealed the potential use of fish gelatin/chitosan GO composites for further implementation in the BTE field.

Graphene oxide reinforcing genipin crosslinked chitosan-gelatin blend films
George Mihail Vlasceanu, Livia Elena Crica, Andreea Madalina Pandele, and Mariana Ionita
MDPI AG
This study was targeted towards the synthesis and characterization of new chitosan–gelatin biocomposite films reinforced with graphene oxide and crosslinked with genipin. The composites’ mode of structuration was characterized by Fourier Transform Infrared spectroscopy and X-ray diffraction, while morphology and topography were investigated by scanning electron microscopy, nano-computer tomography and profilometry. Eventually, thermal stability was evaluated through thermogravimetrical analysis, mechanical properties assessment was carried out to detect potential improvements as a result of graphene oxide (GO) addition and in vitro enzyme degradation was performed to discern the most promising formulations for the maturation of the study towards in vivo assays. In accordance with similar works, results indicated the possibility of using GO as an agent for adjusting films’ roughness, chemical stability and polymer structuration. The enzymatic stability of chitosan–gelatin (CHT-GEL) films was also improved by genipin (GEN) crosslinking and GO supplementation, with the best results being obtained for CHT-GEL-GEN and CHT-GEL-GEN-GO3 (crosslinked formulation with 3 wt.% GO). Yet, contrary to previous reports, no great enhancement of CHT-GEN-GEL-GO thermal performances was obtained by the incorporation of GO.

RECENT SCHOLAR PUBLICATIONS

Advanced Nanobiocomposite Hydrogels Incorporating Organofunctionalized LDH for Soft Tissue Engineering Applications
IC Radu, E Tanasa, S Dinescu, G Vlasceanu, C Zaharia
Polymers 17 (4), 536 2025

MORPHOLOGICAL STUDIES ON CERAMIC SCAFFOLDS BASED ON PRISTINE AND ZINC-DOPED MERWINITE APPLIED TO TISSUE ENGINEERING
FG Ioniță, GM Vlăsceanu, C Busuioc
Book of Abstracts, 87 2024

Fabrication of k-Carrageenan/Alginate/Carboxymethyl Cellulose basedScaffolds via 3D Printing for Potential Biomedical Applications
C Stavarache, A Ghebaur, A Serafim, GM Vlăsceanu, E Vasile, SA Grea, ...
Polymers 16 (11), 1592 2024

Three-dimensional-printed sodium alginate and k-carrageenan-based scaffolds with potential biomedical applications
C Stavarache, SA Gȃrea, A Serafim, E Olăreț, GM Vlăsceanu, MM Marin, ...
Polymers 16 (3), 305 2024

Dual nanofiber and graphene reinforcement of 3D printed biomimetic supports for bone tissue repair
E Cojocaru, M Oprea, GM Vlăsceanu, MC Nicolae, RC Popescu, ...
RSC advances 14 (44), 32517-32532 2024

Advances in therapeutic contact lenses for the management of different ocular conditions
M Ioniță, GM Vlăsceanu, AG Toader, M Manole
Journal of Personalized Medicine 13 (11), 1571 2023

Advances in Therapeutic Contact Lenses for Different Ocular Condition Management
M Ioniță, GM Vlăsceanu, GA Toader, M Manole
2023

Nanoclay-reinforced alginate/salecan composite inks for 3D printing applications
R Ianchis, MM Marin, RL Alexa, IC Gifu, E Alexandrescu, GG Pircalabioru, ...
International Journal of Bioprinting 10 (1), 0967 2023

Double-reinforced fish gelatin composite scaffolds for osteochondral substitutes
AG Toader, GM Vlasceanu, A Serafim, A Banciu, M Ionita
Materials 16 (5), 1815 2023

3D double-reinforced graphene oxide–nanocellulose biomaterial inks for tissue engineered constructs
AI Cernencu, GM Vlasceanu, A Serafim, G Pircalabioru, M Ionita
RSC advances 13 (34), 24053-24063 2023

3D printed composite scaffolds of GelMA and hydroxyapatite nanopowders doped with Mg/Zn ions to evaluate the expression of genes and proteins of osteogenic markers
R Leu Alexa, A Cucuruz, CD Ghițulică, G Voicu, LR Stamat, S Dinescu, ...
Nanomaterials 12 (19), 3420 2022

Chitosan-based materials featuring multiscale anisotropy for wider tissue engineering applications
GM Vlăsceanu, M Ioniță, CC Popescu, ED Giol, I Ionescu, ...
International Journal of Molecular Sciences 23 (10), 5336 2022

3D printable composite biomaterials based on GelMA and hydroxyapatite powders doped with cerium ions for bone tissue regeneration
R Leu Alexa, A Cucuruz, CD Ghițulică, G Voicu, LR Stamat, S Dinescu, ...
International journal of molecular sciences 23 (3), 1841 2022

Graphene-Oxide porous biopolymer hybrids enhance in vitro osteogenic differentiation and promote ectopic osteogenesis in vivo
A Selaru, H Herman, GM Vlasceanu, S Dinescu, S Gharbia, C Balta, ...
International Journal of Molecular Sciences 23 (1) 2022

Graphene–oxide porous biopolymer hybrids enhance in vitro osteogenic differentiation and promote ectopic osteogenesis in vivo
A Șelaru, H Herman, GM Vlăsceanu, S Dinescu, S Gharbia, C Baltă, ...
International Journal of Molecular Sciences 23 (1), 491 2022

Layered clay–graphene oxide nanohybrids for the reinforcement and fire-retardant properties of polyurea matrix
MI Necolau, CM Damian, RC Fierăscu, AL Chiriac, GM Vlăsceanu, ...
Polymers 14 (1), 66 2021

3D printing of alginate-natural clay hydrogel-based nanocomposites
R Leu Alexa, R Ianchis, D Savu, M Temelie, B Trica, A Serafim, ...
Gels 7 (4), 211 2021

5-Aminosalicylic acid loaded chitosan-carrageenan hydrogel beads with potential application for the treatment of inflammatory bowel disease
CE Stavarache, A Ghebaur, S Dinescu, I Samoilă, E Vasile, ...
Polymers 13 (15), 2463 2021

MOST CITED SCHOLAR PUBLICATIONS

Applications and toxicity of silver nanoparticles: a recent review
S Marin, G Mihail Vlasceanu, R Elena Tiplea, I Raluca Bucur, M Lemnaru, ...
Current topics in medicinal chemistry 15 (16), 1596-1604 2015
Citations: 293

Graphene and functionalized graphene: Extraordinary prospects for nanobiocomposite materials
M Ioniţă, GM Vlăsceanu, AA Watzlawek, SI Voicu, JS Burns, H Iovu
Composites Part B: Engineering 121, 34-57 2017
Citations: 187

Graphene inks for the 3D printing of cell culture scaffolds and related molecular arrays
GM Vlăsceanu, H Iovu, M Ioniţă
Composites Part B: Engineering 162, 712-723 2019
Citations: 63

Versatile biomaterial platform enriched with graphene oxide and carbon nanotubes for multiple tissue engineering applications
SR Ignat, AD Lazăr, A Şelaru, I Samoilă, GM Vlăsceanu, M Ioniţă, E Radu, ...
International journal of molecular sciences 20 (16), 3868 2019
Citations: 42

Silver nanoparticles in cancer therapy
GM Vlăsceanu, Ş Marin, RE Ţiplea, IR Bucur, M Lemnaru, MM Marin, ...
Nanobiomaterials in Cancer Therapy, 29-56 2016
Citations: 40

Graphene oxide reinforcing genipin crosslinked chitosan-gelatin blend films
GM Vlasceanu, LE Crica, AM Pandele, M Ionita
Coatings 10 (2), 189 2020
Citations: 36

Versatile graphene biosensors for enhancing human cell therapy
GM Vlăsceanu, RM Amărandi, M Ioniță, T Tite, H Iovu, L Pilan, JS Burns
Biosensors and Bioelectronics 117, 283-302 2018
Citations: 33

Assessment of naturally sourced mineral clays for the 3D printing of biopolymer-based nanocomposite inks
RL Alexa, H Iovu, B Trica, C Zaharia, A Serafim, E Alexandrescu, IC Radu, ...
Nanomaterials 11 (3), 703 2021
Citations: 29

Comprehensive appraisal of graphene–oxide ratio in porous biopolymer hybrids targeting bone-tissue regeneration
GM Vlasceanu, A Șelaru, S Dinescu, C Balta, H Herman, S Gharbia, ...
Nanomaterials 10 (8), 1444 2020
Citations: 25

3D printing of alginate-natural clay hydrogel-based nanocomposites
R Leu Alexa, R Ianchis, D Savu, M Temelie, B Trica, A Serafim, ...
Gels 7 (4), 211 2021
Citations: 24

3D POSS cages decorated 2D graphenic sheets: A versatile platform for silicon-carbonaceous nano-additives design
A Lungu, AI Cernencu, GM Vlasceanu, NM Florea, M Ionita, H Iovu
Composites Part B: Engineering 207, 108578 2021
Citations: 24

Optical graphene-based biosensor for nucleic acid detection; influence of graphene functionalization and ionic strength
DF Becheru, GM Vlăsceanu, A Banciu, E Vasile, M Ioniţă, JS Burns
International Journal of Molecular Sciences 19 (10), 3230 2018
Citations: 24

Predicting the drug loading efficiency into hybrid nanocarriers based on PLGA-vegetable oil using molecular dynamic simulation approach and Flory-Huggins theory
J Ghitman, R Stan, G Vlasceanu, E Vasile, H Iovu
Journal of Drug Delivery Science and Technology 53, 101203 2019
Citations: 17

Nanostructures for Cancer Therapy
AM Grumezescu, A Ficai
Elsevier 2017
Citations: 16