Recent advances in 3D bioprinted tumor models for personalized medicine.

Cancerous tumors are among the most fatal diseases worldwide, claiming nearly 10 million lives in 2020. Due to their complex and dynamic nature, modeling tumors accurately is a challenging task. Current models suffer from inadequate translation between in vitro and in vivo results, primarily due to the isotropic nature of tumors and their microenvironment's relationship. To address these limitations, hydrogel-based 3D bioprinting is emerging as a promising approach to mimic cancer development and behavior. It provides precise control over individual elements' size and distribution within the cancer microenvironment and enables the use of patient-derived tumor cells, rather than commercial lines. Consequently, hydrogel bioprinting is expected to become a state-of-the-art technique for cancer research. This manuscript presents an overview of cancer statistics, current modeling methods, and their limitations. Additionally, we highlight the significance of bioprinting, its applications in cancer modeling, and the importance of hydrogel selection. We further explore the current state of creating models for the five deadliest cancers using 3D bioprinting. Finally, we discuss current trends and future perspectives on the clinical use of cancer modeling using hydrogel bioprinting.

Investigation on Filaments for 3D Printing of Nasal Septum Cartilage Implant.

Septoplasty is a widely used method in treating deviated septum. Although it is successfully implemented, there are problems with excessive bleeding, septal perforation, or infections. The use of anatomically shaped implants could help overcome these problems. This paper focuses on assessing the possibility of the usage of a nasal septum cartilage implant 3D printed from various market-available filaments. Five different types of laments were used, two of which claim to be suitable for medical use. A combination of modeling, mechanical (bending, compression), structural (FTIR), thermal (DSC, MFR), surface (contact angle), microscopic (optical), degradation (2 M HCl, 5 M NaOH, and 0.01 M PBS), printability, and cell viability (MTT) analyses allowed us to assess the suitability of materials for manufacturing implants. Bioflex had the most applicable properties among the tested materials, but despite the overall good performance, cell viability studies showed toxicity of the material in MTT test. The results of the study show that selected filaments were not suitable for nasal cartilage implants. The poor cell viability of Bioflex could be improved by surface modification. Further research on biocompatible elastic materials for 3D printing is needed either by the synthesis of new materials or by modifying existing ones.

Antibacterial Porous Systems Based on Polylactide Loaded with Amikacin.

Three porous matrices based on poly(lactic acid) are proposed herein for the controlled release of amikacin. The materials were fabricated by the method of spraying a surface liquid. Description is given as to the possibility of employing a modifier, such as a silica nanocarrier, for prolonging the release of amikacin, in addition to using chitosan to improve the properties of the materials, e.g., stability and sorption capacity. Depending on their actual composition, the materials exhibited varied efficacy for drug loading, as follows: 25.4 ± 2.2 µg/mg (matrices with 0.05% w/v of chitosan), 93 ± 13 µg/mg (with 0.08% w/v SiO2 amikacin modified nanoparticles), and 96 ± 34 µg/mg (matrices without functional additives). An in vitro study confirmed extended release of the drug (amikacin, over 60 days), carried out in accordance with the mathematical Kosmyer-Pepas model for all the materials tested. The matrices were also evaluated for their effectiveness in inhibiting the growth of bacteria such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent research was conducted on the transdermal absorption, morphology, elemental composition, and thermogravimetric properties of the released drug.

Biomedical engineering of polysaccharide-based tissue adhesives: Recent advances and future direction.

Tissue adhesives have been widely used for preventing wound leaks, sever bleeding, as well as for enhancing drug delivery and biosensing. However, only a few among suggested platforms cover the circumstances required for high-adhesion strength and biocompatibility, without toxicity. Antibacterial properties, controllable degradation, encapsulation capacity, detectability by image-guided procedures and affordable price are also centered to on-demand tissue adhesives. Herein we overview the history of tissue adhesives, different types of polysaccharide-based tissue adhesives, their mechanism of gluing, and different applications of polysaccharide-based tissue adhesives. We also highlight the latest progresses in engineering of tissue adhesives followed by existing challenges in fabrication processes. We argue that future studies have to place focus on a holistic understanding of biomaterials and tissue surface properties, proper fabrication procedures, and development of magnetic and conductive responsive adhesives in order to bridge the huge gap between the present studies for clinical implementation.

Polyurethane based hybrid ciprofloxacin-releasing wound dressings designed for skin engineering purpose.

PURPOSE: Even in the 21st century, chronic wounds still pose a major challenge due to potentially inappropriate treatment options, so the latest wound dressings are hybrid systems that enable clinical management, such as a hybrid of hydrogels, antibiotics and polymers. These wound dressings are mainly used for chronic and complex wounds, which can easily be infected by bacteria. MATERIALS AND METHODS: Six Composite Porous Matrices (CPMs) based on polyurethane (PUR) in alliance with polylactide (PLAs) and poly(vinyl alcohol) (PVA) were prepared and analyzed using optical microscopy. Three different types of hydrogels and their Ciprofloxacin (Cipro) modified variants' ratios were prepared and analyzed using FTIR, SEM and EDX techniques. Six Hybrid Cipro-Releasing Hydrogel Wound Dressings (H-CRWDs) were also prepared and underwent short-term degradation, Cipro release, microbiology and cell viability measurements. RESULTS: Average porosity of CPMs was in the range of 69-81%. The pore size of the obtained CPMs was optimal for skin regeneration. Short-term degradation studies revealed degradability in physiological conditions regardless of sample type. A meaningful release was also observed even in short time (21.76 â€‹± â€‹0.64 â€‹µg/mL after 15 â€‹min). Microbiological tests showed visible inhibition zones. Cell viability tests proved that the obtained H-CRWDs were biocompatible (over 85% of cells). CONCLUSIONS: A promising hybrid wound dressing was labeled. Simple and cost-effective methods were used to obtain microbiologically active and biocompatible dressings. The results were of importance for the design and development of acceptable solutions in the management of chronic wounds of high potential for infection.

Composite Polyurethane-Polylactide (PUR/PLA) Flexible Filaments for 3D Fused Filament Fabrication (FFF) of Antibacterial Wound Dressings for Skin Regeneration.

This paper addresses the potential application of flexible thermoplastic polyurethane (TPU) and poly(lactic acid) (PLA) compositions as a material for the production of antibacterial wound dressings using the Fused Filament Fabrication (FFF) 3D printing method. On the market, there are medical-grade polyurethane filaments available, but few of them have properties required for the fabrication of wound dressings, such as flexibility and antibacterial effects. Thus, research aimed at the production, characterization and modification of filaments based on different TPU/PLA compositions was conducted. The combination of mechanical (tensile, hardness), structural (FTIR), microscopic (optical and SEM), degradation (2 M HCl, 5 M NaOH, and 0.1 M CoCl2 in 20% H2O2) and printability analysis allowed us to select the most promising composition for further antibacterial modification (COMP-7,5PLA). The thermal stability of the chosen antibiotic-amikacin-was tested using processing temperature and HPLC. Two routes were used for the antibacterial modification of the selected filament-post-processing modification (AMI-1) and modification during processing (AMI-2). The antibacterial activity and amikacin release profiles were studied. The postprocessing modification method turned out to be superior and suitable for wound dressing fabrication due to its proven antimicrobial activity against E. coli, P. fluorescens, S. aureus and S. epidermidis bacteria.

Mechanical Properties of Bio-Composites Based on Epoxy Resin and Nanocellulose Fibres.

The aim of our research was to investigate the effect of a small nanocellulose (NC) addition on an improvement of the mechanical properties of epoxy composites. A procedure of chemical extraction from pressed lignin was used to obtain nanocellulose fibers. The presence of nanoparticles in the cellulose pulp was confirmed by FTIR/ATR spectra as well as measurement of nanocellulose particle size using a Zetasizer analyzer. Epoxy composites with NC contents from 0.5% to 1.5% w/w were prepared. The obtained composites were subjected to strength tests, such as impact strength (IS) and resistance to three-point bending with a determination of critical stress intensity factor (Kc). The impact strength of nanocellulose composites doubled in comparison to the unmodified epoxy resin (EP 0). Moreover, Kc was increased by approximately 50% and 70% for the 1.5 and 0.5% w/w NC, respectively. The maximum value of stress at break was achieved at 1% NC concentration in EP and it was 15% higher than that for unmodified epoxy resin. The highest value of destruction energy was characterized by the composition with 0.5% NC and corresponds to the increase of 102% in comparison with EP 0. Based on the analysis of the results it was noted that satisfactory improvement of the mechanical properties of the composite was achieved with a very small addition of nanofiller while other research indicates the need to add much more nanocellulose. It is also expected that this kind of use of raw materials will allow increasing the economic efficiency of the nanocomposite preparation process. Moreover, nanocomposites obtained in this way can be applied as elements of machines or as a modified epoxy matrix for sandwich composites, enabling production of the structure material with reduced weight but improved mechanical properties.

Encapsulation of Amikacin into Microparticles Based on Low-Molecular-Weight Poly(lactic acid) and Poly(lactic acid-co-polyethylene glycol).

The aim of this study was to fabricate novel microparticles (MPs) for efficient and long-term delivery of amikacin (AMI). The emulsification method proposed for encapsulating AMI employed low-molecular-weight poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA-PEG), both supplemented with poly(vinyl alcohol) (PVA). The diameters of the particles obtained were determined as less than 30 µm. Based on an in-vitro release study, it was proven that the MPs (both PLA/PVA- and PLA-PEG/PVA-based) demonstrated long-term AMI release (2 months), the kinetics of which adhered to the Korsmeyer-Peppas model. The loading efficiencies of AMI in the study were determined at the followings levels: 36.5 ± 1.5 µg/mg for the PLA-based MPs and 106 ± 32 µg/mg for the PLA-PEG-based MPs. These values were relatively high and draw parallels with studies published on the encapsulation of aminoglycosides. The MPs provided antimicrobial action against the Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae bacterial strains. The materials were also comprehensively characterized by the following methods: differential scanning calorimetry; gel permeation chromatography; scanning electron microscopy; Fourier transform infrared spectroscopy-attenuated total reflectance; energy-dispersive X-ray fluorescence; and Brunauer-Emmett-Teller surface area analysis. The findings of this study contribute toward discerning new means for conducting targeted therapy with polar, broad spectrum antibiotics.

Processing of Polyester-Urethane Filament and Characterization of FFF 3D Printed Elastic Porous Structures with Potential in Cancellous Bone Tissue Engineering.

This paper addresses the potential of self-made polyester-urethane filament as a candidate for Fused Filament Fabrication (FFF)-based 3D printing (3DP) in medical applications. Since the industry does not provide many ready-made solutions of medical-grade polyurethane filaments, we undertook research aimed at presenting the process of thermoplastic polyurethane (TPU) filament formation, detailed characteristics, and 3DP of specially designed elastic porous structures as candidates in cancellous tissue engineering. Additionally, we examined whether 3D printing affects the structure and thermal stability of the filament. According to the obtained results, the processing parameters leading to the formation of high-quality TPU filament (TPU_F) were captured. The results showed that TPU_F remains stable under the FFF 3DP conditions. The series of in vitro studies involving long- and short-term degradation (0.1 M phosphate-buffered saline (PBS); 5 M sodium hydroxide (NaOH)), cytotoxicity (ISO 10993:5) and bioactivity (simulated body fluid (SBF) incubation), showed that TPU printouts possessing degradability of long-term degradable tissue constructs, are biocompatible and susceptible to mineralization in terms of hydroxyapatite (HAp) formation during SBF exposure. The formation of HAp on the surface of the specially designed porous tissue structures (PTS) was confirmed by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) studies. The compression test of PTS showed that the samples were strengthened due to SBF exposure and deposited HAp on their surface. Moreover, the determined values of the tensile strength (~30 MPa), Young's modulus (~0.2 GPa), and compression strength (~1.1 MPa) allowed pre-consideration of TPU_F for FFF 3DP of cancellous bone tissue structures.

Medical-Grade PCL Based Polyurethane System for FDM 3D Printing-Characterization and Fabrication.

The widespread use of three-dimensional (3D) printing technologies in medicine has contributed to the increased demand for 3D printing materials. In addition, new printing materials that are appearing in the industry do not provide a detailed material characterization. In this paper, we present the synthesis and characterization of polycaprolactone (PCL) based medical-grade thermoplastic polyurethanes, which are suitable for forming in a filament that is dedicated to Fused Deposition Modeling 3D (FDM 3D)printers. For this purpose, we synthesized polyurethane that is based on PCL and 1,6-hexamethylene diisocyanate (HDI) with a different isocyanate index NCO:OH (0.9:1, 1.1:1). Particular characteristics of synthesized materials included, structural properties (FTIR, Raman), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), mechanical and surfaces (contact angle) properties. Moreover, pre-biological tests in vitro and degradation studies were also performed. On the basis of the conducted tests, a material with more desirable properties S-TPU(PCL)0.9 was selected and the optimization of filament forming via melt-extrusion process was described. The initial biological test showed the biocompatibility of synthesized S-TPU(PCL)0.9 with respect to C2C12 cells. It was noticed that the process of thermoplastic polyurethanes (TPU) filaments forming by extrusion was significantly influenced by the appropriate ratio between the temperature profile, rotation speed, and dosage ratio.

Polyurethanes Crosslinked with Poly(vinyl alcohol) as a Slowly-Degradable and Hydrophilic Materials of Potential Use in Regenerative Medicine.

Novel, slowly-degradable and hydrophilic materials with proper mechanical properties and surface characteristics are in great demand within the biomedical field. In this paper, the design, synthesis, and characterization of polyurethanes (PUR) crosslinked with poly(vinyl alcohol) (PVA) as a new proposition for regenerative medicine is described. PVA-crosslinked PURs were synthesized by a two-step polymerization performed in a solvent (dimethylsulfoxide, DMSO). The raw materials used for the synthesis of PVA-crosslinked PURs were poly(ε-caprolactone) (PCL), 1,6-hexamethylene diisocyanate (HDI), and PVA as a crosslinking agent. The obtained materials were studied towards their physicochemical, mechanical, and biological performance. The tests revealed contact angle of the materials surface between 38-47° and tensile strength in the range of 41-52 MPa. Mechanical characteristics of the obtained PURs was close to the characteristics of native human bone such as the cortical bone (TSb = 51-151 MPa) or the cancellous bone (TSb = 10-20 MPa). The obtained PVA-crosslinked PURs did not show significant progress of degradation after 3 months of incubation in a phosphate-buffered saline (PBS). Accordingly, the obtained materials may behave similar to slowly-degradable materials, which can provide long-term physical support in, for example, tissue regeneration, as well as providing a uniform calcium deposition on the material surface, which may influence, for example, bone restoration. A performed short-term hemocompatibility study showed that obtained PVA-crosslinked PURs do not significantly influence blood components, and a cytotoxicity test performed with the use of MG 63 cell line revealed the great cytocompatibility of the obtained materials. According to the performed studies, such PVA-crosslinked PURs may be a suitable proposition for the field of tissue engineering in regenerative medicine.

Fabrication and Characterization of Flexible Medical-Grade TPU Filament for Fused Deposition Modeling 3DP Technology.

The possibility of using additive manufacturing (AM) in the medicine area has created new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU) which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament (F-TPU) properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers.

Microporous Polyurethane Thin Layer as a Promising Scaffold for Tissue Engineering.

The literature describes that the most efficient cell penetration takes place at 200⁻500 µm depth of the scaffold. Many different scaffold fabrication techniques were described to reach these guidelines. One such technique is solvent casting particulate leaching (SC/PL). The main advantage of this technique is its simplicity and cost efficiency, while its main disadvantage is the scaffold thickness, which is usually not less than 3000 µm. Thus, the scaffold thickness is usually far from the requirements for functional tissue reconstruction. In this paper, we report a successful fabrication of the microporous polyurethane thin layer (MPTL) of 1 mm thick, which was produced using SC/PL technique combined with phase separation (PS). The obtained MPTL was highly porous (82%), had pore size in the range of 65⁻426 µm and scaffold average pore size was equal to 154 ± 3 µm. Thus, it can be considered a suitable scaffold for tissue engineering purpose, according to the morphology criterion. Polyurethane (PUR) processing into MPTL scaffold caused significant decrease of contact angle from 78 ± 4° to 56 ± 6° and obtained MPTL had suitable hydrophilic characteristic for mammalian cells growth and tissue regeneration. Mechanical properties of MPTL were comparable to the properties of native tissues. As evidenced by biotechnological examination the MPTL were highly biocompatible with no observed apparent toxicity on mouse embryonic NIH 3T3 fibroblast cells. Performed studies indicated that obtained MPTL may be suitable scaffold candidate for soft TE purposes such as blood vessels.

The Influence of Calcium Glycerophosphate (GPCa) Modifier on Physicochemical, Mechanical, and Biological Performance of Polyurethanes Applicable as Biomaterials for Bone Tissue Scaffolds Fabrication.

In this paper we describe the synthesis of poly(ester ether urethane)s (PEEURs) by using selected raw materials to reach a biocompatible polyurethane (PU) for biomedical applications. PEEURs were synthesized by using aliphatic 1,6-hexamethylene diisocyanate (HDI), poly(ethylene glycol) (PEG), α,ω-dihydroxy(ethylene-butylene adipate) (Polios), 1,4-butanediol (BDO) as a chain extender and calcium glycerolphosphate salt (GPCa) as a modifier used to stimulate bone tissue regeneration. The obtained unmodified (PURs) and modified with GPCa (PURs-M) PEEURs were studied by various techniques. It was confirmed that urethane prepolymer reacts with GPCa modifier. Further analysis of the obtained PURs and PURs-M by Fourier transform infrared (FTIR) and Raman spectroscopy revealed the chemical composition typical for PUs by the confirmed presence of urethane bonds. Moreover, the FTIR and Raman spectra indicated that GPCa was incorporated into the main PU chain at least at one-side. The scanning electron microscopy (SEM) analysis of the PURs-M surface was in good agreement with the FTIR and Raman analysis due to the fact that inclusions were observed only at 20% of its surface, which were related to the non-reacted GPCa enclosed in the PUR matrix as filler. Further studies of hydrophilicity, mechanical properties, biocompatibility, short term-interactions, and calcification study lead to the final conclusion that the obtained PURs-M may by suitable candidate material for further scaffold fabrication. Scaffolds were prepared by the solvent casting/particulate leaching technique (SC/PL) combined with thermally-induced phase separation (TIPS). Such porous scaffolds had satisfactory pore sizes (36⁻100 µm) and porosity (77⁻82%) so as to be considered as suitable templates for bone tissue regeneration.

Gelatin-modified polyurethanes for soft tissue scaffold.

Recently, in the field of biomaterials for soft tissue scaffolds, the interest of their modification with natural polymersis growing. Synthetic polymers are often tough, and many of them do not possess fine biocompatibility. On the other hand, natural polymers are biocompatible but weak when used alone. The combination of natural and synthetic polymers gives the suitable properties for tissue engineering requirements. In our study, we modified gelatin synthetic polyurethanes prepared from polyester poly(ethylene-butylene adipate) (PEBA), aliphatic 1,6-hexamethylene diisocyanate (HDI), and two different chain extenders 1,4-butanediol (BDO) or 1-ethoxy-2-(2-hydroxyethoxy)ethanol (EHEE). From a chemical point of view, we replaced expensive components for building PU, such as 2,6-diisocyanato methyl caproate (LDI) and 1,4-diisocyanatobutane (BDI), with cost-effective HDI. The gelatin was added in situ (in the first step of synthesis) to polyurethane to increase biocompatibility and biodegradability of the obtained material. It appeared that the obtained gelatin-modified PU foams, in which chain extender was BDO, had enhanced interactions with media and their hydrolytic degradation profile was also improved for tissue engineering application. Furthermore, the gelatin introduction had positive impact on gelatin-modified PU foams by increasing their hemocompatibility.

Progress in used tyres management in the European Union: a review.

The dynamic increase in the manufacture of rubber products, particularly those used in the automobile industry, is responsible for a vast amount of wastes, mostly in the form of used tyres, of which more than 17 million tonnes are produced globally each year. The widely differing chemical compositions and the cross-linked structures of rubber in tyres are the prime reason why they are highly resistant to biodegradation, photochemical decomposition, chemical reagents and high temperatures. The increasing numbers of used tyres therefore constitute a serious threat to the natural environment. The progress made in recent years in the management of polymer wastes has meant that used tyres are starting to be perceived as a potential source of valuable raw materials. The development of studies into their more efficient recovery and recycling, and the European Union's restrictive legal regulations regarding the management of used tyres, have led to solutions enabling this substantial stream of rubber wastes to be converted into energy or new polymer materials. In this article we present the relevant literature describing innovative organizational approaches in the management of used tyres in the European Union member countries and the possible uses of waste tyres as a source of raw materials or alternative fossil fuels.