Publications by authors named "Aldo R Boccaccini"

370 Publications

Biomimetic biohybrid nanofibers containing bovine serum albumin as a bioactive moiety for wound dressing.

Mater Sci Eng C Mater Biol Appl 2021 Apr 12;123:111965. Epub 2021 Feb 12.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

For the first time, a biohybrid nanofibrous wound dressing is developed via green electrospinning of a blend solution of bovine serum albumin (BSA) (1 and 3 wt%) and polycaprolactone (PCL). In such a system, the components are miscible and interact through hydrogen bonding between the carbonyl group of PCL and the amine group of BSA, as verified by ATR-FTIR. As a result, the biohybrid nanofibers show a superior elastic modulus and elongation (300% and 58%, respectively) compared with the neat PCL nanofibers. The included protein induces a hydrophilicity effect to the PCL nanofibers, notably at the higher BSA content (3 wt%). In contrast to the neat nanofibers, the biohybrid ones are bioactive and encourage formation of biominerals (made of amorphous calcium carbonate) on the surface, after immersion in simulated body fluid (SBF). Based on the WST-8 cell viability tests, NIH3T3 fibroblast cells were seen to properly interact with the biohybrid mats and to proliferate in their proximity. SEM images show that the cells largely adhere onto such nanofibers even more than they do on the neat ones and adopt a flattened and stretched shape. In addition, the live/dead assay and phalloidin/DAPI staining assay confirm large cell viability and normal cell morphology on the biohybrid nanofiber mats after 4 days incubation. Taken together, BSA/PCL nanofibers are able to offer optimum mechanical properties (elasticity) as well as mineralization which can potentially stimulate the wound healing process, and can be considered a suitable candidate for wound dressing applications.
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http://dx.doi.org/10.1016/j.msec.2021.111965DOI Listing
April 2021

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels.

Biomedicines 2021 Mar 5;9(3). Epub 2021 Mar 5.

IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany.

Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate-gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.
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http://dx.doi.org/10.3390/biomedicines9030261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000907PMC
March 2021

Poly(Glycerol Sebacate) in Biomedical Applications-A Review of the Recent Literature.

Adv Healthc Mater 2021 Mar 17:e2002026. Epub 2021 Mar 17.

Institute of Biomaterials, University Erlangen-Nuremberg, Erlangen, 91058, Germany.

Poly(glycerol sebacate) (PGS) continues to attract attention for biomedical applications owing to its favorable combination of properties. Conventionally polymerized by a two-step polycondensation of glycerol and sebacic acid, variations of synthesis parameters, reactant concentrations or by specific chemical modifications, PGS materials can be obtained exhibiting a wide range of physicochemical, mechanical, and morphological properties for a variety of applications. PGS has been extensively used in tissue engineering (TE) of cardiovascular, nerve, cartilage, bone and corneal tissues. Applications of PGS based materials in drug delivery systems and wound healing are also well documented. Research and development in the field of PGS continue to progress, involving mainly the synthesis of modified structures using copolymers, hybrid, and composite materials. Moreover, the production of self-healing and electroactive materials has been introduced recently. After almost 20 years of research on PGS, previous publications have outlined its synthesis, modification, properties, and biomedical applications, however, a review paper covering the most recent developments in the field is lacking. The present review thus covers comprehensively literature of the last five years on PGS-based biomaterials and devices focusing on advanced modifications of PGS for applications in medicine and highlighting notable advances of PGS based systems in TE and drug delivery.
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http://dx.doi.org/10.1002/adhm.202002026DOI Listing
March 2021

Electrically Conductive and 3D-Printable Oxidized Alginate-Gelatin Polypyrrole:PSS Hydrogels for Tissue Engineering.

Adv Healthc Mater 2021 Mar 12:e2001876. Epub 2021 Mar 12.

Institute of Biomaterials, Department of Material Science and Engineering, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, 91058, Germany.

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli-responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin-content oxidized alginate-gelatin (ADA-GEL) hydrogel is reported, offering 3D-printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA-GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D-printability, and cytocompatibility. It is possible to prepare open-porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D-printable ADA-GEL can be rendered conductive (ADA-GEL-PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical-stimulation assisted tissue engineering.
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http://dx.doi.org/10.1002/adhm.202001876DOI Listing
March 2021

Hierarchical multi-layered scaffolds based on electrofluidodynamic processes for tissue engineering.

Biomed Mater 2021 Mar 10. Epub 2021 Mar 10.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstr. 6, Erlangen, 91058 , GERMANY.

The aim of this study was to obtain hierarchical scaffolds combining 3D printing and two electrofluidodynamic methods. The multi-layered scaffold is composed by 3D printed struts, electrospun fibers obtained from poly(ε-caprolactone) (PCL) and electrosprayed spheres produced from hydrophobically modified chitosan, namely chitosan grafted with linoleic acid (CHLA). Since CHLA has been used for the first time in the electrospraying (EDS) process, the formation of spheres needed an optimization process. The EDS process was strongly affected by the solvent mixture composition, concentration of acid used for CHLA dissolution and solution flow rate. By using the optimized electrospraying conditions, uniformly distributed spheres have been obtained, decorating struts and nanofibers. Preliminary biological tests with mouse preosteoblasts (MC3T3-E1) were performed to investigate the effect of the hierarchical scaffold on cell seeding efficacy. Results showed that the hierarchical structure enhances cell seeding efficacy, respect to the 3D printed struts alone, preventing that the cells passed through the struts during the seeding. Moreover, the addition of the electrosprayed nanoparticles does not affect the cell seeding efficiency. The versatility of the proposed structure, with the added value of CHLA nanoparticles decoration could be suitable for several applications in tissue engineering, mainly related to drug delivery systems.
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http://dx.doi.org/10.1088/1748-605X/abed96DOI Listing
March 2021

Protein Adsorption on SiO-CaO Bioactive Glass Nanoparticles with Controllable Ca Content.

Nanomaterials (Basel) 2021 Feb 24;11(3). Epub 2021 Feb 24.

Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

Bioactive glass nanoparticles (BGNs) are emerging multifunctional building blocks for various biomedical applications. In this study, the primary aim was to develop monodispersed binary SiO-CaO BGNs with controllable Ca content. We successfully synthesized such spherical BGNs (size ~110 nm) using a modified Stöber method. Our results showed that the incorporated Ca did not significantly affect particle size, specific surface area, and structure of BGNs. Concentrations of CaO in BGN compositions ranging from 0 to 10 mol% could be obtained without the gap between actual and nominal compositions. For this type of BGNs (specific surface area 30 m/g), the maximum concentration of incorporated CaO appeared to be ~12 mol%. The influence of Ca content on protein adsorption was investigated using bovine serum albumin (BSA) and lysozyme as model proteins. The amount of adsorbed proteins increased over time at the early stage of adsorption (<2 h), regardless of glass composition and protein type. Further incubation of BGNs with protein-containing solutions seemed to induce a reduced amount of adsorbed proteins, which was more significant in BGNs with higher Ca content. The results indicate that the Ca content in BGNs is related to their protein adsorption behavior.
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http://dx.doi.org/10.3390/nano11030561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995967PMC
February 2021

Differential Responses to Bioink-Induced Oxidative Stress in Endothelial Cells and Fibroblasts.

Int J Mol Sci 2021 Feb 26;22(5). Epub 2021 Feb 26.

Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Endowed Professorship for Nanomedicine, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

A hydrogel system based on oxidized alginate covalently crosslinked with gelatin (ADA-GEL) has been utilized for different biofabrication approaches to design constructs, in which cell growth, proliferation and migration have been observed. However, cell-bioink interactions are not completely understood and the potential effects of free aldehyde groups on the living cells have not been investigated. In this study, alginate, ADA and ADA-GEL were characterized via FTIR and NMR, and their effect on cell viability was investigated. In the tested cell lines, there was a concentration-dependent effect of oxidation degree on cell viability, with the strongest cytotoxicity observed after 72 h of culture. Subsequently, primary human cells, namely fibroblasts and endothelial cells (ECs) were grown in ADA and ADA-GEL hydrogels to investigate the molecular effects of oxidized material. In ADA, an extremely strong ROS generation resulting in a rapid depletion of cellular thiols was observed in ECs, leading to rapid necrotic cell death. In contrast, less pronounced cytotoxic effects of ADA were noted on human fibroblasts. Human fibroblasts had higher cellular thiol content than primary ECs and entered apoptosis under strong oxidative stress. The presence of gelatin in the hydrogel improved the primary cell survival, likely by reducing the oxidative stress via binding to the CHO groups. Consequently, ADA-GEL was better tolerated than ADA alone. Fibroblasts were able to survive the oxidative stress in ADA-GEL and re-entered the proliferative phase. To the best of our knowledge, this is the first report that shows in detail the relationship between oxidative stress-induced intracellular processes and alginate di-aldehyde-based bioinks.
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http://dx.doi.org/10.3390/ijms22052358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956320PMC
February 2021

Fabrication of Quasi-2D Shape-Tailored Microparticles using Wettability Contrast-Based Platforms.

Adv Mater 2021 Apr 28;33(14):e2007695. Epub 2021 Feb 28.

Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, Aveiro, 3810-193, Portugal.

The ability to fabricate materials with ultrathin architectures enables the breakthrough of low-dimensional structures with high surface area that showcase distinctive properties from their bulk counterparts. They are exploited in a wide range of fields, including energy harvesting, catalysis, and biomedicine. Despite such versatility, the fine tuning of the lateral dimensions and geometry of these structures remains challenging. Prepatterned platforms gain significant attention as enabling technologies to process materials with highly controlled shapes and dimensions. Herein, different nanometer-thick particles of various lateral sizes and geometries (e.g., squares, circles, triangles, hexagons) are processed with high precision and definition, taking advantage of the wettability contrast of oleophilic-oleophobic patterned surfaces. Quasi-2D polymeric microparticles with high shape- and size-fidelity can be retrieved as freestanding objects in a single step. These structures show cell-mediated pliability, and their integration in gravity-enforced human adipose-derived stem cell spheroids leads to an enhanced metabolic activity and a modulated secretion of proangiogenic factors.
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http://dx.doi.org/10.1002/adma.202007695DOI Listing
April 2021

Comparative Study of the Antimicrobial Activity of Selenium Nanoparticles With Different Surface Chemistry and Structure.

Front Bioeng Biotechnol 2020 25;8:624621. Epub 2021 Jan 25.

Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Belgrade, Serbia.

Although selenium nanoparticles (SeNPs) have gained attention in the scientific community mostly through investigation of their anticancer activity, a great potential of this nanomaterial was recognized recently regarding its antimicrobial activity. The particle form, size, and surface chemistry have been recognized as crucial parameters determining the interaction of nanomaterials with biological entities. Furthermore, considering a narrow boundary between beneficial and toxic effects for selenium per se, it is clear that investigations of biomedical applications of SeNPs are very demanding and must be done with great precautions. The goal of this work is to evaluate the effects of SeNPs surface chemistry and structure on antimicrobial activity against several common bacterial strains, including (ATCC 6538), (ATCC 29212), (ATCC 6633), and (ATCC 9341), as well as (ATCC 8739), Abony (NCTC 6017), (NCIMB 9111) and (ATCC 9027), and the standard yeast strain (ATCC 10231). Three types of SeNPs were synthesized by chemical reduction approach using different stabilizers and reducing agents: (i) bovine serum albumin (BSA) + ascorbic acid, (ii) chitosan + ascorbic acid, and (iii) with glucose. A thorough physicochemical characterization of the obtained SeNPs was performed to determine the effects of varying synthesis parameters on their morphology, size, structure, and surface chemistry. All SeNPs were amorphous, with spherical morphology and size in the range 70-300 nm. However, the SeNPs obtained under different synthesis conditions, i.e. by using different stabilizers as well as reducing agents, exhibited different antimicrobial activity as well as cytotoxicity which are crucial for their applications. In this paper, the antimicrobial screening of the selected systems is presented, which was determined by the broth microdilution method, and inhibitory influence on the production of monomicrobial and dual-species biofilm was evaluated. The potential mechanism of action of different systems is proposed. Additionally, the cytotoxicity of SeNPs was examined on the MRC-5 cell line, in the same concentration interval as for antimicrobial testing. It was shown that formulation SeNPs-BSA expressed a significantly lower cytotoxic effect than the other two formulations.
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http://dx.doi.org/10.3389/fbioe.2020.624621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869925PMC
January 2021

Cellular Response to Sol-Gel Hybrid Materials Releasing Boron and Calcium Ions.

ACS Biomater Sci Eng 2021 02 26;7(2):491-506. Epub 2021 Jan 26.

Department of Materials and Ceramic Engineering, CICECO-Aveiro Institute of Materials (CICECO/UA), University of Aveiro, 3810-193 Aveiro, Portugal.

Poly(dimethylsiloxane) (PDMS)-SiO-CaO-based hybrid materials prepared by sol-gel have proved to be very promising materials for tissue engineering applications and drug-delivery systems. These hybrids are biocompatible and present osteogenic and bioactive properties supporting osteoblast attachment and bone growth. The incorporation of therapeutic elements in these materials, such as boron (B) and calcium (Ca), was considered in this study as an approach to develop biomaterials capable of stimulating bone regeneration. The main purpose of this work was thus to produce, by sol-gel, bioactive and biocompatible hybrid materials of the PDMS-SiO-BO-CaO system, capable of a controlled Ca and B release. Different compositions with different boron amounts were prepared using the same precursors resulting in different monolithic materials, with distinct structures and microstructures. Structural features were assessed by Fourier transform infrared (FT-IR) spectrometry and solid-state nuclear magnetic resonance (NMR) techniques, which confirmed the presence of hybrid bonds (Si-O-Si) between organic (PDMS) and inorganic phase (tetraethyl orthosilicate (TEOS)), as well as borosiloxane bonds (B-O-Si). From the B NMR results, it was found that Ca changes the boron coordination, from trigonal (BO) to tetrahedral (BO). Scanning electron microscopy (SEM) micrographs and N isotherms showed that the incorporation of boron modifies the material's microstructure by increasing the macroporosity and decreasing the specific surface area (SSA). In vitro tests in simulated body fluid (SBF) showed the precipitation of a calcium phosphate layer on the material surface and the controlled release of therapeutic ions. The cytocompatibility of the prepared hybrids was studied with bone marrow stromal cells (ST-2 cell line) by analyzing the cell viability and cell density. The results demonstrated that increasing the dilution rate of extraction medium from the hybrids leads to improved cell behavior. The relationship between the in vitro response and the structural and microstructural features of the materials was explored. It was shown that the release of calcium and boron ions, determined by the hybrid structure was crucial for the observed cells behavior. Although not completely understood, the encouraging results obtained constitute an incentive for further studies on this topic.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01546DOI Listing
February 2021

Hemp Fiber Reinforced Red Mud/Fly Ash Geopolymer Composite Materials: Effect of Fiber Content on Mechanical Strength.

Materials (Basel) 2021 Jan 21;14(3). Epub 2021 Jan 21.

Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany.

Novel hemp fiber reinforced geopolymer composites were fabricated. The matrix was a new geopolymer based on a mixture of red mud and fly ash. Chopped, randomly oriented hemp fibers were used as reinforcement. The mechanical properties of the geopolymer composite, such as diametral tensile (DTS) (or Brazilian tensile) strength and compressive strength (CS), were measured. The geopolymer composites reinforced with 9 vol.% and 3 vol.% hemp fiber yielded average DTS values of 5.5 MPa and average CS values of 40 MPa. Scanning electron microscopy (SEM) studies were carried out to evaluate the microstructure and fracture surfaces of the composites. The results indicated that the addition of hemp fiber is a promising approach to improve the mechanical strength as well as to modify the failure mechanism of the geopolymer, which changed from brittle to "pseudo-ductile."
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http://dx.doi.org/10.3390/ma14030511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865735PMC
January 2021

Ionically and Enzymatically Dual Cross-Linked Oxidized Alginate Gelatin Hydrogels with Tunable Stiffness and Degradation Behavior for Tissue Engineering.

ACS Biomater Sci Eng 2020 07 12;6(7):3899-3914. Epub 2020 Jun 12.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany.

Hydrogels that allow for the successful long-term culture of cell-biomaterial systems to enable the maturation of tissue engineering constructs are highly relevant in regenerative medicine. Naturally derived polysaccharide-based hydrogels promise to be one material group with enough versatility and chemical functionalization capability to tackle the challenges associated with long-term cell culture. We report a marine derived oxidized alginate, alginate dialdehyde (ADA), and gelatin (GEL) system (ADA-GEL), which is cross-linked ionic (Ca) and enzymatic (microbial transglutaminase, mTG) interaction to form dually cross-linked hydrogels. The cross-linking approach allowed us to tailor the stiffness of the hydrogels in a wide range (from <5 to 120 kPa), without altering the initial ADA and GEL hydrogel chemistry. It was possible to control the degradation behavior of the hydrogels to be stable for up to 30 days of incubation. Increasing concentrations of mTG cross-linker solutions allowed us to tune the degradation behavior of the ADA-GEL hydrogels from fast (<7 days) to moderate (14 days) and slow (>30 days) degradation kinetics. The cytocompatibility of mTG cross-linked ADA-GEL was assessed using NIH-3T3 fibroblasts and ATDC-5 mouse teratocarcinoma cells. Both cell types showed highly increased cellular attachment on mTG cross-linked ADA-GEL in comparison to Ca cross-linked hydrogels. In addition, ATDC-5 cells showed a higher proliferation on mTG cross-linked ADA-GEL hydrogels in comparison to tissue culture polystyrene control substrates. Further, the attachment of human umbilical vein endothelial cells (HUVEC) on ADA-GEL (+) mTG was confirmed, proving the suitability of mTG+Ca cross-linked ADA-GEL for several cell types. Summarizing, a promising platform to control the properties of ADA-GEL hydrogels is presented, with the potential to be applied in long-term cell culture investigations such as cartilage, bone, and blood-vessel engineering, as well as for biofabrication.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00677DOI Listing
July 2020

Synthesis and Characterization of Mesoporous Mg- and Sr-Doped Nanoparticles for Moxifloxacin Drug Delivery in Promising Tissue Engineering Applications.

Int J Mol Sci 2021 Jan 8;22(2). Epub 2021 Jan 8.

School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Mesoporous silica-based nanoparticles (MSNs) are considered promising drug carriers because of their ordered pore structure, which permits high drug loading and release capacity. The dissolution of Si and Ca from MSNs can trigger osteogenic differentiation of stem cells towards extracellular matrix calcification, while Mg and Sr constitute key elements of bone biology and metabolism. The aim of this study was the synthesis and characterization of sol-gel-derived MSNs co-doped with Ca, Mg and Sr. Their physico-chemical properties were investigated by X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence spectroscopy (XRF), Brunauer Emmett Teller and Brunauer Joyner Halenda (BET/BJH), dynamic light scattering (DLS) and ζ-potential measurements. Moxifloxacin loading and release profiles were assessed with high performance liquid chromatography (HPLC) cell viability on human periodontal ligament fibroblasts and their hemolytic activity in contact with human red blood cells (RBCs) at various concentrations were also investigated. Doped MSNs generally retained their textural characteristics, while different compositions affected particle size, hemolytic activity and moxifloxacin loading/release profiles. All co-doped MSNs revealed the formation of hydroxycarbonate apatite on their surface after immersion in simulated body fluid (SBF) and promoted mitochondrial activity and cell proliferation.
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http://dx.doi.org/10.3390/ijms22020577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827177PMC
January 2021

Biofabrication and Characterization of Alginate Dialdehyde-Gelatin Microcapsules Incorporating Bioactive Glass for Cell Delivery Application.

Macromol Biosci 2020 10 17;20(10):e2000138. Epub 2020 Aug 17.

Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstr. 6, 91058, Erlangen, Germany.

The effect of the incorporation of 45S5 bioactive glass (BG) microparticles (mean particle size ≈ 2 µm) on the fabrication and physicochemical properties of alginate dialdehyde-gelatin hydrogel capsules is investigated. The addition of BG particles decreases the hydrogel gelation time by ≈79% and 91% for the samples containing 0.1% w/v and 0.5% w/v BG, respectively. Moreover, it results in increasing average diameter of hydrogel capsules produced via a pressure-driven extrusion technique from about 1000 µm for the samples without BG to about 1700 and 1900 µm for the samples containing BG at concentrations of 0.1% w/v and 0.5% w/v, respectively. The presence of BG particles in the capsules decreases the degradation rate and improves the bioactivity of the materials. The viability of MG-63 cells encapsulated in all samples increases during the first 7 d of cultivation and maintains the same level during 21 d of cultivation. The early cell viability in samples containing BG is lower than that in samples without BG. The results show that 45S5 BG can positively regulate the osteogenic activity of cells incorporated in hydrogel capsules. The fabricated composite capsules exhibit promising potential for cell delivery in bone regeneration applications.
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http://dx.doi.org/10.1002/mabi.202000138DOI Listing
October 2020

A New Generation of Electrospun Fibers Containing Bioactive Glass Particles for Wound Healing.

Materials (Basel) 2020 Dec 11;13(24). Epub 2020 Dec 11.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany.

Chitosan fibers blended with polyethylene oxide (CHIT_PEO) and crosslinked with genipin were fabricated by electrospinning technique. Subsequently, CHIT_PEO bioactive glass composite electrospun mats were fabricated with the aim to achieve flexible structures with adequate mechanical properties and improved biological performance respect to CHIT_PEO fibers, for potential applications in wound healing. Three different compositions of bioactive glasses (BG) were selected and investigated: 45S5 BG, a Sr and Mg containing bioactive glass (BGMS10) and a Zn-containing bioactive glass (BGMS_2Zn). Particulate BGs (particles size < 20 μm) were separately added to the starting CHIT_PEO solution before electrospinning. The two recently developed bioactive glasses (BGMS10 and BGMS_2Zn) showed very promising biological properties in terms of bioactivity and cellular viability; thus, such compositions were added for the first time to CHIT_PEO solution to fabricate composite electrospun mats. The incorporation of bioactive glass particles and their distribution into CHIT_PEO fibers were assessed by SEM and FTIR analyses. Furthermore, CHIT_PEO composite electrospun mats showed improved mechanical properties in terms of Young's Modulus compared to neat CHIT_PEO fibers; on the contrary, the values of tensile strain at break (%) were comparable. Biological performance in terms of cellular viability was investigated by means of WST-8 assay and CHIT_PEO composite electrospun mats showed cytocompatibility and the desired cellular viability.
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http://dx.doi.org/10.3390/ma13245651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763513PMC
December 2020

Effect of manganese, zinc, and copper on the biological and osteogenic properties of mesoporous bioactive glass nanoparticles.

J Biomed Mater Res A 2020 Dec 1:e37136. Epub 2020 Dec 1.

Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, Germany.

Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro-osteogenic properties. Therefore, the concentration-dependent impact of MBGNs (composition in mol%: 70 SiO , 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO , 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow-derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn-doped MBGNs (5Mn-MBGNs) showed a small "therapeutic window" with a dose-dependent negative impact on cell viability but increasing pro-osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn-MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu-doped MBGNs (5Cu-MBGNs). Furthermore, 5Cu-MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches.
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http://dx.doi.org/10.1002/jbm.a.37136DOI Listing
December 2020

Potential of laponite incorporated oxidized alginate-gelatin (ADA-GEL) composite hydrogels for extrusion-based 3D printing.

J Biomed Mater Res B Appl Biomater 2020 Dec 5. Epub 2020 Dec 5.

Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen, Germany.

The concept of adding inorganic fillers into hydrogels to form hydrogel nanocomposites often provides advantageous properties which can be exploited for successful 3D biofabrication. In this study, a new composite hydrogel combining oxidized alginate-gelatin (ADA-GEL) hydrogel and laponite nanoclay as inorganic nanofiller was successfully developed and characterized. The results showed that the addition of 0.5% (wt/vol) laponite nanoplatelets improved the printability of ADA-GEL hydrogels enabling the fabrication of detailed structures since a low effect of material spreading and reduced tendency to pore closure appeared. Furthermore, a comparison of different needle types (cylindrical and conical; same inner diameter of 250 μm) in filament fusion test showed that the pattern dispensed by cylindrical tip has enhanced printing accuracy and pattern fidelity when compared with the pattern from conical tip. A glass flip test determined a processing window of 1-2 h after composite ink preparation. Overall, laponite/ADA-GEL hydrogel composites are confirmed as promising inks for 3D bioprinting.
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http://dx.doi.org/10.1002/jbm.b.34771DOI Listing
December 2020

Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells.

Biomed Mater 2020 Dec 1. Epub 2020 Dec 1.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstr. 6, Erlangen, 91058, GERMANY.

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO2 (0.05MCe-MBGNs, composition in mol%: 86.6SiO-12.1CaO-1.3CeO; and 0.2MCe-MBGNs, composition in mol%: 86.0SiO-11.8CaO-2.2CeO) and unmodified MBGNs (composition in mol%: 86SiO-14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs' IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of this in-vitro study show that Ce-doped MBGNs are attractive candidates for further application in BTE.
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http://dx.doi.org/10.1088/1748-605X/abcf5fDOI Listing
December 2020

3D printing of bioreactors in tissue engineering: A generalised approach.

PLoS One 2020 30;15(11):e0242615. Epub 2020 Nov 30.

Department Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, Würzburg, Germany.

3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703892PMC
January 2021

Antibacterial, pro-angiogenic and pro-osteointegrative zein-bioactive glass/copper based coatings for implantable stainless steel aimed at bone healing.

Bioact Mater 2021 May 13;6(5):1479-1490. Epub 2020 Nov 13.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany.

Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) , a natural fibroblast-friendly polymer, (ii) , a pro-osteogenic inorganic material and (iii) , an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed where the growth of biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed.
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http://dx.doi.org/10.1016/j.bioactmat.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674162PMC
May 2021

In-vitro mechanical and biological evaluation of novel zirconia reinforced bioglass scaffolds for bone repair.

J Mech Behav Biomed Mater 2021 02 6;114:104164. Epub 2020 Nov 6.

Ceramic and Composite Materials Research Group (CERMAT), Federal University of Santa Catarina (UFSC), Campus Trindade, Florianópolis, SC, Brazil; Center for MicroElectroMechanical Systems (CMEMS-UMINHO), University of Minho, Campus de Azurém, 4800-058, Guimarães, Braga, Portugal; School of Dentistry (DODT), Postgraduate Program in Dentistry (PPGO), Federal University of Santa Catarina, Campus Trindade, 88040-900, Florianópolis, SC, Brazil. Electronic address:

Bone defects resulting from infections, tumors, or traumas represent a major health care issue. Tissue engineering has been working togehter with medicine to develop techniques to repair bone damage and increase patient's life quality. In that context, scaffolds composed of bioactive ceramics have been explored, although their poor mechanical properties restrain their clinical applications as highly porous structures. As an alternative solution, this study aimed to evaluate the mechanical properties and biological response of novel zirconia reinforced bioactive glass scaffolds (ZRBG) manufactured by the replica method. The microstructure, chemical composition, compressive strength, density, in-vitro bioactivity, and cell viability were analyzed and compared to scaffolds made of monolithic zirconia of similar architecture (45, 60 and 85 ppi). The microstructure of ZRGB scaffolds consisted of a bioactive glass matrix with dispersed zirconia particles (~33% glassy phase) and the compressive strength values (ZRBG scaffolds: 0.33 ± 0.11, 0.41 ± 0.20 and 0.48 ± 0.6 MPa; ZRBG scaffolds with extra BG coating: 0.38 ± 0.13, 0.45 ± 0.11 and 0.50 ± 0.14 MPa for 45, 60 and 80 ppi, respectively) were not statistically different from those of zirconia scaffolds (0.25 ± 0.14 MPa for 45 ppi, 0.32 ± 0.11 MPa for 60 ppi and 0.44 ± 0.07 MPa for 80 ppi). No bioactivity was exhibited by monolithic zirconia scaffolds while significant bioactive response was found for ZRBG scaffolds. The cell viability of ZRBG scaffolds in osteogenic medium was improved up to 171% over zirconia scaffolds. This work provides promosing results for further exploring this technique for implant dentistry.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104164DOI Listing
February 2021

14-3-3ε protein-loaded 3D hydrogels favor osteogenesis.

J Mater Sci Mater Med 2020 Nov 3;31(11):105. Epub 2020 Nov 3.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany.

3D printing has emerged as vanguard technique of biofabrication to assemble cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissues. In this work, gelatin methacrylate (GelMA)/alginate hydrogel scaffolds were obtained by 3D printing and 14-3-3ε protein was encapsulated in the hydrogel to induce osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASC). GelMA/alginate-based grid-like structures were printed and remained stable upon photo-crosslinking. The viscosity of alginate allowed to control the pore size and strand width. A higher viscosity of hydrogel ink enhanced the printing accuracy. Protein-loaded GelMA/alginate-based hydrogel showed a clear induction of the osteogenic differentiation of hASC cells. The results are relevant for future developments of GelMA/alginate for bone tissue engineering given the positive effect of 14-3-3ε protein on both cell adhesion and proliferation.
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http://dx.doi.org/10.1007/s10856-020-06434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609425PMC
November 2020

Rational Design of a Triple-Layered Coaxial Extruder System: and Evaluations Directed Toward Optimizing Cell Viability.

Int J Bioprint 2020 24;6(4):282. Epub 2020 Jul 24.

Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen 91058, Germany.

Biofabrication is a rapidly evolving field whose main goal is the manufacturing of three-dimensional (3D) cell-laden constructs that closely mimic tissues and organs. Despite recent advances on materials and techniques directed toward the achievement of this goal, several aspects such as tissue vascularization and prolonged cell functionality are limiting bench-to-bedside translation. Extrusion-based 3D bioprinting has been devised as a promising biofabrication technology to overcome these limitations, due to its versatility and wide availability. Here, we report the development of a triple-layered coaxial nozzle for use in the biomanufacturing of vascular networks and vessels. The design of the coaxial nozzle was first optimized toward guaranteeing high cell viability upon extrusion. This was done with the aid of evaluations and their subsequent experimental validation by investigating the bioprinting of an alginate-based bioink. Results confirmed that the values for pressure distribution predicted by experiments resulted in cell viabilities above 70% and further demonstrated the effect of layer thickness and extrusion pressure on cell viability. Our work paves the way for the rational design of multi-layered coaxial extrusion systems to be used in biofabrication approaches to replicate the very complex structures found in native organs and tissues.
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http://dx.doi.org/10.18063/ijb.v6i4.282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557338PMC
July 2020

Fabrication and characterization of Ag- and Ga-doped mesoporous glass-coated scaffolds based on natural marine sponges with improved mechanical properties.

J Biomed Mater Res A 2020 Oct 21. Epub 2020 Oct 21.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany.

Natural marine sponges were used as sacrificial template for the fabrication of bioactive glass-based scaffolds. After sintering at 1050°C, the resulting samples were additionally coated with a silicate solution containing biologically active ions (Ag and Ga), well-known for their antibacterial properties. The produced scaffolds were characterized by superior mechanical properties (maximum compressive strength of 4 MPa) and total porosity of ~80% in comparison to standard scaffolds made by using PU foam templates. Direct cell culture tests performed on the uncoated and coated samples showed positive results in terms of adhesion, proliferation, and differentiation of MC3T3-E1 cells. Moreover, vascular endothelial growth factor (VEGF) secretion from cells in contact with scaffold dissolution products was measured after 7 and 10 days of incubation, showing promising angiogenic results for bone tissue engineering applications. The antibacterial potential of the produced samples was assessed by performing agar diffusion tests against both Gram-positive and Gram-negative bacteria.
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http://dx.doi.org/10.1002/jbm.a.37123DOI Listing
October 2020

Numerical Simulations as Means for Tailoring Electrically Conductive Hydrogels Towards Cartilage Tissue Engineering by Electrical Stimulation.

Molecules 2020 Oct 16;25(20). Epub 2020 Oct 16.

Institute of General Electrical Engineering, University of Rostock, 18051 Rostock, Germany.

Cartilage regeneration is a clinical challenge. In recent years, hydrogels have emerged as implantable scaffolds in cartilage tissue engineering. Similarly, electrical stimulation has been employed to improve matrix synthesis of cartilage cells, and thus to foster engineering and regeneration of cartilage tissue. The combination of hydrogels and electrical stimulation may pave the way for new clinical treatment of cartilage lesions. To find the optimal electric properties of hydrogels, theoretical considerations and corresponding numerical simulations are needed to identify well-suited initial parameters for experimental studies. We present the theoretical analysis of a hydrogel in a frequently used electrical stimulation device for cartilage regeneration and tissue engineering. By means of equivalent circuits, finite element analysis, and uncertainty quantification, we elucidate the influence of the geometric and dielectric properties of cell-seeded hydrogels on the capacitive-coupling electrical field stimulation. Moreover, we discuss the possibility of cellular organisation inside the hydrogel due to forces generated by the external electric field. The introduced methodology is easily reusable by other researchers and allows to directly develop novel electrical stimulation study designs. Thus, this study paves the way for the design of future experimental studies using electrically conductive hydrogels and electrical stimulation for tissue engineering.
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http://dx.doi.org/10.3390/molecules25204750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587583PMC
October 2020

A Review on Natural Fiber-Reinforced Geopolymer and Cement-Based Composites.

Materials (Basel) 2020 Oct 16;13(20). Epub 2020 Oct 16.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

The use of ecological materials for building and industrial applications contributes to minimizing the environmental impact of new technologies. In this context, the cement and geopolymer sectors are considering natural fibers as sustainable reinforcement for developing composites. Natural fibers are renewable, biodegradable, and non-toxic, and they exhibit attractive mechanical properties in comparison with their synthetic fiber counterparts. However, their hydrophilic character makes them vulnerable to high volumes of moisture absorption, thus conferring poor wetting with the matrix and weakening the fiber-matrix interface. Therefore, modification and functionalization strategies for natural fibers to tailor interface properties and to improve the durability and mechanical behavior of cement and geopolymer-based composites become highly important. This paper presents a review of the physical, chemical and biological pre-treatments that have been performed on natural fibers, their results and effects on the fiber-matrix interface of cement and geopolymer composites. In addition, the degradation mechanisms of natural fibers used in such composites are discussed. This review finalizes with concluding remarks and recommendations to be addressed through further in-depth studies in the field.
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http://dx.doi.org/10.3390/ma13204603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602782PMC
October 2020

Hybrid gelatin/oxidized chondroitin sulfate hydrogels incorporating bioactive glass nanoparticles with enhanced mechanical properties, mineralization, and osteogenic differentiation.

Bioact Mater 2021 Mar 6;6(3):890-904. Epub 2020 Oct 6.

Institute of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.

Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior. However, these hydrogels suffer from low mechanical properties, uncontrolled degradation, and insufficient osteogenic activity, which limits their applications in bone regeneration. In this study, we developed hybrid gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogels that incorporated mesoporous bioactive glass nanoparticles (MBGNs) as bioactive fillers for bone regeneration. Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax. The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation. The gelation time decreased with increasing the concentration of MBGNs added. Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength. The injectability of the hydrogels was not significantly affected by the MBGN incorporation. Also, the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs. The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities.
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http://dx.doi.org/10.1016/j.bioactmat.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548431PMC
March 2021

Synthesis and Characterization of Citrate-Stabilized Gold-Coated Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications.

Molecules 2020 Sep 26;25(19). Epub 2020 Sep 26.

Department of Otorhinolaryngology-Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, Universitätsklinikum, 91054 Erlangen, Germany.

Surface-functionalized gold-coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) may be a useful tool in various biomedical applications. To obtain Au-SPIONs, gold salt was precipitated onto citrate-stabilized SPIONs (Cit-SPIONs) using a simple, aqueous one-pot technique inspired by the Turkevich method of gold nanoparticle synthesis. By the further stabilization of the Au-SPION surface with additional citrate (Cit-Au-SPIONs), controllable and reproducible Z-averages enhanced long-term dispersion stability and moderate dispersion pH values were achieved. The citrate concentration of the reaction solution and the gold/iron ratio was found to have a major influence on the particle characteristics. While the gold-coating reduced the saturation magnetization to 40.7% in comparison to pure Cit-SPIONs, the superparamagnetic behavior of Cit-Au-SPIONs was maintained. The formation of nanosized gold on the SPION surface was confirmed by X-ray diffraction measurements. Cit-Au-SPION concentrations of up to 100 µg Fe/mL for 48 h had no cytotoxic effect on Jurkat cells. At a particle concentration of 100 µg Fe/mL, Jurkat cells were found to take up Cit-Au-SPIONs after 24 h of incubation. A significantly higher attachment of thiol-containing L-cysteine to the particle surface was observed for Cit-Au-SPIONs (53%) in comparison to pure Cit-SPIONs (7%).
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http://dx.doi.org/10.3390/molecules25194425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583944PMC
September 2020

Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing.

Adv Healthc Mater 2020 10 16;9(20):e2000905. Epub 2020 Sep 16.

Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, 91058, Germany.

Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented.
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http://dx.doi.org/10.1002/adhm.202000905DOI Listing
October 2020

Electrospun PCL Fiber Mats Incorporating Multi-Targeted B and Co Co-Doped Bioactive Glass Nanoparticles for Angiogenesis.

Materials (Basel) 2020 Sep 10;13(18). Epub 2020 Sep 10.

Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany.

Vascularization is necessary in tissue engineering to keep adequate blood supply in order to maintain the survival and growth of new tissue. The synergy of biologically active ions with multi-target activity may lead to superior angiogenesis promotion in comparison to single-target approaches but it has been rarely investigated. In this study, polycaprolactone (PCL) fiber mats embedded with B and Co co-doped bioactive glass nanoparticles (BCo.BGNs) were fabricated as a tissue regeneration scaffold designed for promoting angiogenesis. BCo.NBGs were successfully prepared with well-defined spherical shape using a sol-gel method. The PCL fiber mats embedding co-doped bioactive glass nanoparticles were fabricated by electrospinning using benign solvents. The Young's moduli of the nanoparticle containing PCL fiber mats were similar to those of the neat fiber mats and suitable for scaffolds utilized in soft tissue repair approaches. The mats also showed non-cytotoxicity to ST-2 cells. PCL fiber mats containing BCo.BGNs with a relatively high content of B and Co promoted the secretion of vascular endothelial growth factor to a greater extent than PCL fiber mats with a relatively low B and Co contents, which demonstrates the potential of dual ion release (B and Co) from bioactive glasses to enhance angiogenesis in soft tissue engineering.
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http://dx.doi.org/10.3390/ma13184010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557727PMC
September 2020