How to fix a broken heart-designing biofunctional cues for effective, environmentally-friendly cardiac tissue engineering.

Cardiovascular diseases bear strong socioeconomic and ecological impact on the worldwide healthcare system. A large consumption of goods, use of polymer-based cardiovascular biomaterials, and long hospitalization times add up to an extensive carbon footprint on the environment often turning out to be ineffective at healing such cardiovascular diseases. On the other hand, cardiac cell toxicity is among the most severe but common side effect of drugs used to treat numerous diseases from COVID-19 to diabetes, often resulting in the withdrawal of such pharmaceuticals from the market. Currently, most patients that have suffered from cardiovascular disease will never fully recover. All of these factors further contribute to the extensive negative toll pharmaceutical, biotechnological, and biomedical companies have on the environment. Hence, there is a dire need to develop new environmentally-friendly strategies that on the one hand would promise cardiac tissue regeneration after damage and on the other hand would offer solutions for the fast screening of drugs to ensure that they do not cause cardiovascular toxicity. Importantly, both require one thing-a mature, functioning cardiac tissue that can be fabricated in a fast, reliable, and repeatable manner from environmentally friendly biomaterials in the lab. This is not an easy task to complete as numerous approaches have been undertaken, separately and combined, to achieve it. This review gathers such strategies and provides insights into which succeed or fail and what is needed for the field of environmentally-friendly cardiac tissue engineering to prosper.

Anticancer and antibacterial properties of carbon nanotubes are governed by their functional groups.

Due to their high strength, low weight, and biologically-inspired dimensions, carbon nanotubes have found wide interest across all of medicine. In this study, four types of highly dispersible multi-walled carbon nanotubes (CNTs) of similar dimensions, but slightly different chemical compositions, were compared with an unmodified material to verify the impact their surface chemistry has on cytocompatibility, anticancer, inflammation, and antibacterial properties. Minute changes in the chemical composition were found to greatly affect the biological performance of the CNTs. Specifically, the CNTs with a large number of carbon atoms with a +2 coordination number induced cytotoxicity in macrophages and melanoma cells, and had a moderate antibacterial effect against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria strains, all while being cytocompatible towards human dermal fibroblasts. Moreover, substituting some of the OH groups with ammonia diminished their cytotoxicity towards macrophages while still maintaining the aforementioned positive qualities. At the same time, CNTs with a large number of carbon atoms with a +3 coordination number had a high innate cytocompatibility towards normal healthy cells but were toxic towards cancer cells and bacteria. The latter was further boosted by reacting the CNTs' carboxyl groups with ammonia. Although requiring further analyses, the results of this study, thus, introduce new CNTs that without drugs can treat cancer, inflammation, and/or infection while still remaining cytocompatible with mammalian cells.

Biomimetic biphasic curdlan-based scaffold for osteochondral tissue engineering applications - Characterization and preliminary evaluation of mesenchymal stem cell response in vitro.

Osteochondral defects remain a huge problem in medicine today. Biomimetic bi- or multi-phasic scaffolds constitute a very promising alternative to osteochondral autografts and allografts. In this study, a new curdlan-based scaffold was designed for osteochondral tissue engineering applications. To achieve biomimetic properties, it was enriched with a protein component - whey protein isolate as well as a ceramic ingredient - hydroxyapatite granules. The scaffold was fabricated via a simple and cost-efficient method, which represents a significant advantage. Importantly, this technique allowed generation of a scaffold with two distinct, but integrated phases. Scanning electron microcopy and optical profilometry observations demonstrated that phases of biomaterial possessed different structural properties. The top layer of the biomaterial (mimicking the cartilage) was smoother than the bottom one (mimicking the subchondral bone), which is beneficial from a biological point of view because unlike bone, cartilage is a smooth tissue. Moreover, mechanical testing showed that the top layer of the biomaterial had mechanical properties close to those of natural cartilage. Although the mechanical properties of the bottom layer of scaffold were lower than those of the subchondral bone, it was still higher than in many analogous systems. Most importantly, cell culture experiments indicated that the biomaterial possessed high cytocompatibility towards adipose tissue-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells in vitro. Both phases of the scaffold enhanced cell adhesion, proliferation, and chondrogenic differentiation of stem cells (revealing its chondroinductive properties in vitro) as well as osteogenic differentiation of these cells (revealing its osteoinductive properties in vitro). Given all features of the novel curdlan-based scaffold, it is worth noting that it may be considered as promising candidate for osteochondral tissue engineering applications.

Fly Ash as an Eco-Friendly Filler for Rigid Polyurethane Foams Modification.

There is currently a growing demand for more effective thermal insulation materials with the best performance properties. This research paper presents the investigation results on the influence of two types of filler on the structure and properties of rigid polyurethane foam composites. Fly ash as a product of coal combustion in power plants and microspheres of 5, 10, 15, and 20 wt.%, were used as rigid polyurethane foams modifiers. The results of thermal analysis, mechanical properties testing, and cellular structure investigation performed for polyurethane composites show that the addition of fly ash, up to 10 wt.%, significantly improved the majority of the tested parameters. The use of up to 20 wt.% of microspheres improves the mechanical and thermal properties and thermal stability of rigid polyurethane foams.

Covalently bonded surface functional groups on carbon nanotubes: from molecular modeling to practical applications.

The aim of this work was to investigate how chemical functionalization affects the electronic properties of multi-walled carbon nanotubes, altering the electrophoretic deposition process: a method of choice for the fabrication of high quality, all-carbon nanotube (CNT) layers. Wet chemistry methods were applied to modify the surfaces of CNTs by insertion of various oxygen- and nitrogen-containing groups. Transmission electron microscopy revealed no significant changes in the material morphology, while X-ray photoelectron spectroscopy and Raman spectroscopy showed that changes in the chemical composition did not translate to the changes in the structure. Molecularly modelled optimized surface functional group geometries and electron density distributions allowed the calculation of the dipole moments (-COOH = 0.77; -OH = 1.65; -CON(CH3CH2)2 = 3.33; -CONH2 = 2.00; -NH2 = 0.78). Due to their polarity, the introduction of surface functional groups resulted in significant modifications of the electronic properties of CNTs, as elucidated by work function measurements via the Kelvin method and ultraviolet photoelectron spectroscopy. The work function changed from 4.6 eV (raw CNTs) to 4.94 eV for the -OH functionalized CNTs and 4.3 eV for the CNTs functionalized with -CON(CH3CH2), and was inversely proportional to the dipole moment values. Finally, using CNT dispersions, electrophoretic deposition was conducted, allowing the correlation of the work function of CNTs and the measured electrophoretic current with the impact on the deposits' qualities. Thus, a rational background for the development of carbon-based biomaterials was provided.

Superabsorbent curdlan-based foam dressings with typical hydrocolloids properties for highly exuding wound management.

Effective management of chronic wounds with excessive exudate may be challenging for medical doctors. Over the years, there has been an increasing interest in the engineering of biomaterials, focusing on the development of polymer-based wound dressings to accelerate the healing of exuding wounds. The aim of this study was to use curdlan, which is known to support wound healing, as a base for the production of superabsorbent hybrid biomaterials (curdlan/agarose and curdlan/chitosan) with the intended use as wound dressings for highly exuding wound management. To evaluate the biomedical potential of the fabricated curdlan-based biomaterials, they were subjected to a comprehensive assessment of their microstructural, physicochemical, and biological properties. The obtained results showed that foam-like biomaterials with highly porous structure (66-77%) transform into soft gel after contact with the wound fluid, acting as typical hydrocolloid dressings. Novel biomaterials have the superabsorbent ability (1 g of the biomaterial absorbs approx. 15 ml of exudate) with horizontal wicking direction while keeping dry edges, and show water vapor transmission rate of approx. 1700-1800 g/m2/day which is recommended for optimal wound healing. Moreover, they are stable in the presence of collagenases, but prone to biodegradation in lysozyme solution (simulated infected wound environment). Importantly, the developed biomaterials are non-toxic and their surface hinders fibroblast attachment, which is essential during dressing changes to avoid damage to newly formed tissues in the wound bed. All mentioned features make the developed biomaterials promising candidates to be used as the wound dressings for the management of chronic wounds with moderate to high exudate.

Advances in Fabricating the Electrospun Biopolymer-Based Biomaterials.

Biopolymers formed into a fibrous morphology through electrospinning are of increasing interest in the field of biomedicine due to their intrinsic biocompatibility and biodegradability and their ability to be biomimetic to various fibrous structures present in animal tissues. However, their mechanical properties are often unsatisfactory and their processing may be troublesome. Thus, extensive research interest is focused on improving these qualities. This review article presents the selection of the recent advances in techniques aimed to improve the electrospinnability of various biopolymers (polysaccharides, polynucleotides, peptides, and phospholipids). The electrospinning of single materials, and the variety of co-polymers, with and without additives, is covered. Additionally, various crosslinking strategies are presented. Examples of cytocompatibility, biocompatibility, and antimicrobial properties are analyzed. Special attention is given to whey protein isolate as an example of a novel, promising, green material with good potential in the field of biomedicine. This review ends with a brief summary and outlook for the biomedical applicability of electrospinnable biopolymers.

Conductive all-carbon nanotube layers: Results on attractive physicochemical, anti-bacterial, anticancer and biocompatibility properties.

Physicochemical, electrochemical and biological performance of 4 types of all-carbon nanotube layers was studied. Higher oxidation state of carbon was responsible for micro-scaled uniformity of the layers and excellent electrical conductivity, while nitrogen containing functional groups yielded materials with anisotropy similar to natural tissues and reduced work function. All materials were cytocompatible with mammalian fibroblasts (viability >80%, cytotoxicity <3% at day 7) and human dermal fibroblast (viability of cells >70% at day 1), while reducing bacterial and cancer cells proliferation without adding any drug. After 8 h culture, a ~50% depletion in the number of Gram-positive bacteria was observed on materials with lower work function, while Gram-negative bacteria were more sensitive towards carbon coordination number and presence of nitrogen atoms (cell depletion of up to 48% on amidized carbon nanotubes). After 1-day culture, >80% reduction in the melanoma cells number, connected with enhanced production of reactive oxygen species (ROS) was observed. All-carbon nanotube layers decreased bacteria and cancer cell functions without negatively influencing mammalian cells nor using drugs and we believe that this can be explained by various sensitivity of the tested cells towards exogenous ROS overproduction. As the concerns over implant-related infections as well as rates of antibiotic-resistant bacteria and chemotherapeutic-resistant cancer cells are growing, such materials should pave the way for a wide range of biomedical applications.

Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer.

Cancer is one of the biggest healthcare concerns in our century, a disease whose treatment has become even more difficult following reports of drug-resistant tumors. When this happens, chemotherapy treatments fail or decrease in efficiency, leading to catastrophic consequences to the patient. This discovery, along with the fact that drug resistance limits the efficacy of current treatments, has led to a new wave of discovery for new methods of treatment. The use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in cancer. Research in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive targeting. Consequently, these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better targeting. This review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers, including polymeric, viral, lipid-based, metal-based, carbon-based, and magnetic nanocarriers, opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors.

Elastic and biodegradable chitosan/agarose film revealing slightly acidic pH for potential applications in regenerative medicine as artificial skin graft.

The aim of this work was to develop new method for the production of chitosan/agarose (CHN/A) film that could serve as a potential artificial skin substitute for regenerative medicine applications. Within this new production method, the concentrations of biomaterial components (chitosan in CH3COOH and agarose in NaOH) were optimized to provide neutralization of the resultant mixture up to pH approx. 6.0 without uncontrolled precipitation (gelation) of chitosan constituent. Produced thin film was subjected to comprehensive evaluation of its biomedical potential by determination of mechanical, physicochemical, and biological properties. It was demonstrated that the developed CHN/A film reveals slightly acidic pH of 5.98 known to support skin regeneration, high exudate absorption capacity, and is prone to biodegradation in simulated enzymatic wound environment. Performed tensile test proved high elastic deformations of the film (Young's modulus = 0.02 MPa, elongation at break = 23%) in a wet state, which would allow suitable stretching after application at the wound site. Moreover, novel biomaterial is non-toxic and supports fibroblast growth on its surface. Based on the obtained results it may be concluded that the produced CHN/A film possesses all necessary features of the artificial skin substitute.

Novel chitosan/agarose/hydroxyapatite nanocomposite scaffold for bone tissue engineering applications: comprehensive evaluation of biocompatibility and osteoinductivity with the use of osteoblasts and mesenchymal stem cells.

BACKGROUND: Nanocomposites produced by reinforcement of polysaccharide matrix with nanoparticles are widely used in engineering of biomaterials. However, clinical applications of developed novel biomaterials are often limited due to their poor biocompatibility. PURPOSE: The aim of this work was to comprehensively assess biocompatibility of highly macroporous chitosan/agarose/nanohydroxyapatite bone scaffolds produced by a novel method combining freeze-drying with a foaming agent. Within these studies, blood plasma protein adsorption, osteoblast (MC3T3-E1 Subclone 4 and hFOB 1.19) adhesion and proliferation, and osteogenic differentiation of mesenchymal stem cells derived from bone marrow and adipose tissue were determined. The obtained results were also correlated with materials' surface chemistry and wettability to explain the observed protein and cellular response. RESULTS: Obtained results clearly showed that the developed nanocomposite scaffolds were characterized by high biocompatibility and osteoconductivity. Importantly, the scaffolds also revealed osteoinductive properties since they have the ability to induce osteogenic differentiation (Runx2 synthesis) in undifferentiated mesenchymal stem cells. The surface of biomaterials is extremely hydrophilic, prone to protein adsorption with the highest affinity toward fibronectin binding, which allows for good osteoblast adhesion, spreading, and proliferation. CONCLUSION: Produced by a novel method, macroporous nanocomposite biomaterials have great potential to be used in regenerative medicine for acceleration of the bone healing process.

Ion-exchanging dialysis as an effective method for protein entrapment in curdlan hydrogel.

The purpose of this study was to determine whether dialysis method allows for efficient protein entrapment in curdlan-based hydrogel. Thus, bovine serum albumin, a model of bioactive protein, was incorporated into curdlan matrix using ion-exchanging dialysis method against two concentrations of CaCl2 solution - 2% and 10%, respectively. Then, physicochemical, mechanical, and biological properties of the bovine serum albumin-loaded curdlan hydrogels were evaluated. Received results show that neither the polymer nor the entrapment procedure change the bovine serum albumin conformation (as proven by Fourier transform infrared spectroscopy and circular dichroism spectroscopy) and the process guarantees high protein entrapment efficiency (above 95%). The curdlan-based carrier obtained against 2% of CaCl2 solution was found to possess higher swelling ability, release greater amounts of bovine serum albumin (up to 4 weeks), and exhibit superior biocompatibility compared to curdlan-based carrier obtained against 10% of CaCl2 solution. Thus, dialysis method enables efficient protein entrapment in curdlan hydrogel and obtained protein carrier via dialysis method into 2% of CaCl2 solution may be considered as a promising protein delivery system especially for tissue engineering applications. It should be noted that we are the first who presented effective method for protein entrapment in curdlan hydrogel.

Fluidized bed combustion fly ash as filler in composite polyurethane materials.

Fly ash (FA) is a waste material having great potential as modifier of mechanical and thermal properties in polyurethane (PUR) technology. There are very few reporting the use of fluidized bed combustion (FBC) FA in the production of PUR foams. In this work, authors have used the as received FBC FA as an additive to PUR rigid foams. The composite materials containing 5, 10, 15, and 20 wt% of FA were obtained by hand mixing and casting method. Microscopic observations of both unmodified and composite foams showed a well formed, cellular structure of the rigid foam. The cell structure was uniform; most of the cells were closed, which was an important parameter influencing thermal insulation properties of PUR materials. FA was uniformly distributed within PUR matrix and placed between cells. When the content of FA in composite foams increased, cells' dimensions decreased, which suggested that FA particles acted as nucleation sites during the foam formation process. The absorption bands presented in IR spectrum of PUR foam confirmed the presence of urethane bonds in the unmodified foam material. The IR spectrum of as-received FA reconfirmed the crystalline phases recognized by XRD analysis, which were anhydrite, quartz, lime, calcite and aluminosilicate. No additional bands were observed which suggested that no chemical bonding between PUR matrix and FA particles occurred in the composite foam. The incorporation of FA into the PUR matrix, up to 10 wt%, improved the mechanical performance of the composite materials, when compared to unmodified PUR foam. Such a tendency suggested the occurrence of interfacial interactions between polymer matrix and FA particles, as well as the uniform distribution of the filler within PUR material. For all the materials analyzed, the addition of FA to PUR foam reduced both carbon content and the gross calorific value. The addition of FA improved the thermal stability of the PUR foam material (barrier effect of the FA prevented the release of gases from the foam structure).

The use of calcium ions instead of heat treatment for ß-1,3-glucan gelation improves biocompatibility of the ß-1,3-glucan/HA bone scaffold.

The aim of this study was to determine which procedure for ß-1,3-glucan gelation - newly developed dialysis against calcium salt or described in the literature thermal technique - is more appropriate for fabrication of a biomaterial designed for bone tissue engineering applications. Thus, ß-1,3-glucan/hydroxyapatite scaffolds were prepared based on two different methods and their physicochemical, microstructural, and biological properties were compared. Obtained results demonstrated that unlike thermal method-prepared ß-1,3-glucan/hydroxyapatite material (glu/HAT), bone scaffold fabricated via dialysis method (glu/HA D) possessed rough surface resulting from the presence of CaCl2 precipitates as proven by SEM and EDS analysis. As a consequence, glu/HA D scaffold released Ca2+ ions to the surrounding environment positively affecting osteoblast behaviour and biomineralization in vitro. Since glu/HA D material exhibited better bioactivity and biocompatibility compared to the glu/HA T scaffold, it may be concluded that the dialysis method is more suitable for ß-1,3-glucan/hydroxyapatite biomaterial fabrication.

Hybrid chitosan/ß-1,3-glucan matrix of bone scaffold enhances osteoblast adhesion, spreading and proliferation via promotion of serum protein adsorption.

Initial protein adsorption to the material surface is crucial for osteoblast adhesion, survival, and rapid proliferation resulting in intensive new bone formation. The aim of this study was to demonstrate that modification of a chitosan matrix of chitosan/hydroxyapatite (chit/HA) biomaterial for bone tissue engineering applications with linear ß-1,3-glucan (curdlan) leads to promotion of serum protein adsorption to the resultant scaffold (chit/glu/HA) and thus in enhancement of osteoblast adhesion, spreading and proliferation. Fabricated biomaterials were pre-adsorbed with different protein solutions and then protein adsorption and osteoblast behavior on the scaffolds were compared. Moreover, surface chemical composition, wettability and surface energy of biomaterials were compared. Modification of the chitosan matrix with ß-1,3-glucan introduces a greater polarpart in the resultant chitosan/ß-1,3-glucan matrix presumably resulting from more OH groups within the curdlan structure. Moreover, FTIR-ATR results suggest that there might be some sort of chemical interaction between the NH group of chitosan and the OH group of ß-1,3-glucan. As a consequence, the chit/glu/HA scaffold adsorbs significantly more adhesion proteins that are crucial for osteoblasts compared to the chit/HA material, providing a higher density culture of well-spread osteoblasts on its surface. Obtained results revealed that not only is chit/glu/HA biomaterial a promising scaffold for bone tissue engineering applications, but the specific polysaccharide chit/glu matrix itself is promising for use in the biomedical material field to modify various biomaterials in order to enhance osteoblast adhesion and proliferation on their surfaces.

On the influence of various physicochemical properties of the CNTs based implantable devices on the fibroblasts' reaction in vitro.

Coating the material with a layer of carbon nanotubes (CNTs) has been a subject of particular interest for the development of new biomaterials. Such coatings, made of properly selected CNTs, may constitute an implantable electronic device that facilitates tissue regeneration both by specific surface properties and an ability to electrically stimulate the cells. The goal of the presented study was to produce, evaluate physicochemical properties and test the applicability of highly conductible material designed as an implantable electronic device. Two types of CNTs with varying level of oxidation were chosen. The process of coating involved suspension of the material of choice in the diluent followed by the electrophoretic deposition to fabricate layers on the surface of a highly biocompatible metal-titanium. Presented study includes an assessment of the physicochemical properties of the material's surface along with an electrochemical evaluation and in vitro biocompatibility, cytotoxicity and apoptosis studies in contact with the murine fibroblasts (L929) in attempt to answer the question how the chemical composition and CNTs distribution in the layer alters the electrical properties of the sample and whether any of these properties have influenced the overall biocompatibility and stimulated adhesion of fibroblasts. The results indicate that higher level of oxidation of CNTs yielded materials more conductive than the metal they are deposited on. In vitro study revealed that both materials were biocompatible and that the cells were not affected by the amount of the functional group and the morphology of the surface they adhered to.

Titanium coated with functionalized carbon nanotubes--a promising novel material for biomedical application as an implantable orthopaedic electronic device.

The aim of the study was to fabricate titanium (Ti) material coated with functionalized carbon nanotubes (f-CNTs) that would have potential medical application in orthopaedics as an implantable electronic device. The novel biomedical material (Ti-CNTs-H2O) would possess specific set of properties, such as: electrical conductivity, non-toxicity, and ability to inhibit connective tissue cell growth and proliferation protecting the Ti-CNTs-H2O surface against covering by cells. The novel material was obtained via an electrophoretic deposition of CNTs-H2O on the Ti surface. Then, physicochemical, electrical, and biological properties were evaluated. Electrical property evaluation revealed that a Ti-CNTs-H2O material is highly conductive and X-ray photoelectron spectroscopy analysis demonstrated that there are mainly COOH groups on the Ti-CNTs-H2O surface that are found to inhibit cell growth. Biological properties were assessed using normal human foetal osteoblast cell line (hFOB 1.19). Conducted cytotoxicity tests and live/dead fluorescent staining demonstrated that Ti-CNTs-H2O does not exert toxic effect on hFOB cells. Moreover, fluorescence laser scanning microscope observation demonstrated that Ti-CNTs-H2O surface retards to a great extent cell proliferation. The study resulted in successful fabrication of highly conductive, non-toxic Ti-CNTs-H2O material that possesses ability to inhibit osteoblast proliferation and thus has a great potential as an orthopaedic implantable electronic device.

Degradation of glycine and alanine on irradiated quartz.

Recent researches suggest participation of minerals in the formation of life under primordial conditions. Among all of the minerals, quartz seems to be one of the most probable to take part in such processes. However, an external source of energy is needed, e.g. electric discharge. A device simulating the proposed conditions was designed and was used to simulate prebiotic conditions. Investigation of processes occurring during the stimulation of quartz with electric discharge was studied by means of Ultraviolet-visible (UV-VIS) spectroscopy, in order to monitor the generation kinetics of free radicals. Additionally, infrared spectroscopy was applied to identify chemical reaction products created in a solution of alanine or glycine, in the presence of quartz treated with electric discharge. Formation of increased amounts of free radicals, compared to experiments performed without quartz and/or amino acid, is reported, along with identification of possible degradation products of alanine. No synthetic reactions were observed.