Dorota Kołbuk

Electrospinning of gelatin for tissue engineering – molecular conformation as one of the overlooked problems

Gelatin is one of the most promising materials in tissue engineering as a scaffold component. This biopolymer indicates biocompatibility and bioactivity caused by the existence of specific amino acid sequences, being preferred sites for interactions with cells, with high similarity to natural extracellular matrix. The present paper does not aspire to be a full review of electrospinning of gelatin and gelatin containing nanofibers as scaffolds in tissue engineering. It is focused on the still open question of the role of the higher order structures of gelatin in scaffold’s bioactivity/functionality. Gelatin molecules can adopt various conformations depending on temperature, solvent, pH, etc. Our review indicates the potential ways for formation of α-helix conformation during electrospinning and the methods of further structure stabilization. It is intuitively expected that the native α-helix conformation appearing as a result of partial renaturation of gelatin can be beneficial from the viewpoint of bioactivity of scaffolds, providing thus a much cheaper alternative approach as opposed to expensive electrospinning of native collagen.

The Effect of Selected Electrospinning Parameters on Molecular Structure of Polycaprolactone Nanofibers

The effect of electrospinning parameters on morphology, molecular, and supermolecular structure of polycaprolactone (PCL) fibers was analyzed, with respect to tissue engineering applications. Fibers morphology and structure are mainly determined by solution concentration and collector type. Applied voltage does not significantly influence supermolecular structure (crystallinity) and mechanical stiffness. There is correlation between changes in structure and proliferation of 3T3 cells as evidenced by in vitro study. Processing window of optimal scaffolds is relatively wide, however, variation of electrospinning parameters do not significantly affect their biological functionality. GRAPHICAL ABSTRACT

Development of electrospun poly (vinyl alcohol)-based bionanocomposite scaffolds for bone tissue engineering

The article is focused on the role of nanohydroxy apatite (nHAp) and cellulose nanofibers (CNFs) as fillers in the electrospun poly (vinyl alcohol) (ES-PVA) nanofibers for bone tissue engineering (TE). Fibrous scaffolds of PVA, PVA/nHAp (10 wt.%), and PVA/nHAp(10 wt.%)/CNF(3 wt.%) were successfully fabricated and characterized. Tensile test on electrospun PVA/nHAp10 and PVA/nHAp10/CNF3 revealed a three-fold and seven-fold increase in modulus compared with pure ES-PVA (45.45 ± 4.77). Although, nanofiller loading slightly reduced the porosity percentage, all scaffolds had porosity higher than 70%. In addition, contact angle test proved the great hydrophilicity of scaffolds. The presence of fillers reduced in vitro biodegradation rate in PBS while accelerates biomineralization in simulated body fluid (SBF). Furthermore, cell viability, cell attachment, and functional activity of osteoblast MG-63 cells were studied on scaffolds showing higher cellular activity for scaffolds with nanofillers. Generally, the obtained results confirm that the 3-componemnt fibrous scaffold of PVA/nHAp/CNF has promising potential in hard TE.

Structure and properties of polycaprolactone/chitosan nonwovens tailored by solvent systems

Electrospinning of chitosan blends is a reasonable idea to prepare fibre mats for biomedical applications. Synthetic and natural components provide, for example, appropriate mechanical strength and biocompatibility, respectively. However, solvent characteristics and the polyelectrolyte nature of chitosan influence the spinnability of these blends. In order to compare the effect of solvent on polycaprolactone/chitosan fibres, two types of the most commonly used solvent systems were chosen, namely 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and acetic acid (AA)/formic acid (FA). Results obtained by various experimental methods clearly indicated the effect of the solvent system on the structure and properties of electrospun polycaprolactone/chitosan fibres. Viscosity measurements confirmed different polymer-solvent interactions. Various molecular interactions resulting in different macromolecular conformations of chitosan influenced its spinnability and properties. HFIP enabled fibres to be obtained whose average diameter was less than 250 nm while maintaining the brittle and hydrophilic character of the nonwoven, typical for the chitosan component. Spectroscopy studies revealed the formation of chitosan salts in the case of the AA/FA solvent system. Chitosan salts visibly influenced the structure and properties of the prepared fibre mats. The use of AA/FA caused a reduction of Youngs modulus and wettability of the proposed blends. It was confirmed that wettability, mechanical properties and the antibacterial effect of polycaprolactone/chitosan fibres may be tailored by selecting an appropriate solvent system. The MTT cell proliferation assay revealed an increase of cytotoxicity to mouse fibroblasts in the case of 25% w/w of chitosan in electrospun nonwovens.

Morphology and surface chemistry of bicomponent scaffolds in terms of mesenchymal stromal cell viability

Biological interaction between cells and scaffolds is mediated through events at surfaces. Proteins present in the culture medium adsorb on substrates, generating a protein adlayer that triggers further downstream events governing cell adhesion. Polymer blends often combine the properties of the individual components, for example, can provide mechanical as well as surface properties in one fibre. Therefore, mixtures of synthetic polycaprolactone and gelatin as a denatured form of collagen were electrospun at selected conditions and polymer weight ratios. Fibre morphologies and chemical properties of the surfaces were analysed. These scaffolds were seeded with human mesenchymal stromal cells and their viability was studied. Gelatin addition to polycaprolactone leads to a reduction in fibre diameter. A linear increase in gelatin at the fibre surface was observed in function of the weighed polymers, except for polycaprolactone/gelatin fibres incorporating equal weight ratios. Thereby, a depletion of gelatin at the fibre surface is stated for equally mixed polymers. The depletion of gelatin at the fibre surface is most probably due to hydrophobic interactions between hydrophobic segments of polycaprolactone and gelatin, affecting the spinning mechanism and thus fibre structure. Furthermore, polycaprolactone/gelatin blends show enhanced wettability properties compared to pure gelatin, at least partly due to molecular segregation. Results of in vitro studies reveal an increase in cellular viability and proliferation for cells cultivated on nanofibres containing gelatin, caused by the cell-attractive surface composition as well as the hydrophilic nature of the scaffolds. Contact guidance of cells seeded on parallelised fibres is observed, and DNA tests show evidently enhanced cell numbers on nanofibres containing 20 wt% of gelatin.

Information transmission efficiency in neuronal communication systems

The nature and efficiency of brain transmission processes, its high reliability and efficiency is one of the most elusive area of contemporary science [1]. We study information transmission efficiency by considering a neuronal communication as a Shannon-type channel. Thus, using high quality entropy estimators, we evaluate the mutual information between input and output signals. We assume model of neuron proposed by Levy and Baxter [2], which incorporates all essential qualitative mechanisms participating in neural transmission process. We analyze how the synaptic failure, activation threshold and characteristics of the input source affect the efficiency. Two types of network architectures are considered. We start by a single-layer feedforward network and next we study brain-like networks which contains components such as excitatory and inhibitory neurons or long-range connections. It turned out that, especially for lower activation thresholds, significant synaptic noise can lead even to twofold [Figure ​[Figure1]1] increase of the transmission efficiency [3]. Moreover, the more amplifying the amplitude fluctuation is, the more positive is the role of synaptic noise [4]. Our research also shows that all brain-like network components, in broad range of conditions, significantly improve the information-energetic efficiency. It turned out that inhibitory neurons can improve the information-energetic transmission efficiency by 50 percent, while long-range connections can improve the efficiency even by 70 percent. The knowledge of the effects of the long-range connections could be particulary useful when we consider possible reconstruction or support of them applying biomaterials [5,6]. We also showed that the most effective is the network with the smallest size: we found that two times increase of the size can cause even three times decrease of the information-energetic efficiency [7]. Figure 1 Mutual information dependency on synaptic success, s, in single-layer neural network. Maximal mutual information values (dotted line) and these achieved at s = 1 (solid). Size of a given dot is proportional to 1−s, indicating the bigger the dot, ...

Injectable hydrogels as novel materials for central nervous system regeneration

APPROACH Injuries of the central nervous system (CNS) can cause serious and permanent disability due to limited regeneration ability of the CNS. Presently available therapies are focused on lesion spreading inhibition rather than on tissue regeneration. Recent investigations in the field of neural tissue engineering indicate extremely promising properties of novel injectable and non-injectable hydrogels which are tailored to serve as biodegradable scaffolds for CNS regeneration. OBJECTIVE This review discusses the state-of-the-art and barriers in application of novel polymer-based hydrogels without and with nanoparticles for CNS regeneration. MAIN RESULTS Pure hydrogels suffer from lack of similarities to natural neural tissue. Many of the biological studies indicated nano-additives in hydrogels may improve their topography, mechanical properties, electroconductivity and biological functions. The most promising biomaterials which meet the requirements of CNS tissue engineering seem to be injectable thermosensitive hydrogels loaded with specific micro-and nanoparticles. SIGNIFICANCE We highlight injectable hydrogels with various micro-and nanoparticles, because of novelty and attractiveness of this type of materials for CNS regeneration and future development perspectives.

Injectable hydrogels and nanocomposite hydrogels for cartilage regeneration: INJECTABLE HYDROGELS AND NANOCOMPOSITE HYDROGELS FOR CARTILAGE REGENERATION

Cartilage loss due to age-related degeneration and mechanical trauma is a significant and challenging problem in the field of surgical medicine. Unfortunately, cartilage tissue can be characterized by the lack of regenerative ability. Limitations of conventional treatment strategies, such as auto-, allo-, and xenografts or implants stimulate an increasing interest in the tissue engineering approach to cartilage repair. This review discusses the application of polymer-based scaffolds, with an emphasis on hydrogels in cartilage tissue engineering. We highlight injectable hydrogels with various micro- and nanoparticles, as they constitute a novel and attractive type of scaffolds. We discuss advantages, limitations, and future perspectives of injectable nanocomposite hydrogels for cartilage tissue regeneration.

Articular cartilage: New directions and barriers of scaffolds development – review

ABSTRACT Despite progress which has been made in recent years in the field of cell-based therapies or cell scaffolds for cartilage regeneration, a lot of work still needs to be done. Scaffolds remain a great base for tissue regeneration. However, proper implantation procedures or post-treatment still await development. In this review we summarize paths of cartilage treatment, especially focusing on cell scaffold design and manufacture. As well as the advantages and disadvantages of available or investigated methods and materials, especially focusing on cartilage scaffold design. We show the most promising directions and barriers in the creation of healthy tissue. GRAPHICAL ABSTRACT

Tailoring of Architecture and Intrinsic Structure of Electrospun Nanofibers by Process Parameters for Tissue Engineering Applications

Electrospinning process is commercially used to form nanofibers as scaffolds in tissue engineering. Similarities in morphology of electrospun nanofibers to the natural extracellular matrix, flexibility, and low cost of the process contribute to their use in regeneration of cartilage, ligaments/tendons, muscles, and bones. Required properties are tailored by the use of appropriate polymers: polyesters, their copolymers, blends with natural biopolymers such as gelatin, collagen, chitosan, or composites with nanoparticles. In the case of one component fibers, factors strongly influencing the final diameter of the electrospinning jet include volumetric charge density, distance between the needle and the collector, needle diameter, and viscosity. A moderate effect is exerted by initial polymer concentration, solution density, electric potential, and solvent vapor pressure. In the case of blend fibers, the w/w% ratio of mixed polymers is an additional parame‐ ter of the electrospinning process. Addition of gelatin, collagen, and/or chitosan influence the solution properties and, in consequence, fiber diameter, mechanical properties, wettability, chemical structure, crystallinity, etc. Cellular response de‐ pends on electrospun fibers’ tailored morphology, chemical structure as well as mechanical properties. Electrospinning process is one of the success stories in nanotechnologies during the last few years. Understanding of electrospinning process parameters enables tailoring of electrospun nanofibers morphology, internal structure, and properties to appropriate application. This opens up new possibilities in tissue engineering.