Preparation Of Scaffolds Research Articles

A novel method for coating calcium phosphate with trace elements extracted from bone using electrical stimulation

Hydroxyapatite (HAp) is a biomaterial used because of its high potential for improving the healing of bone fractures. HAp is typically prepared using synthetic methods. However, synthetic HAp generally does not contain trace elements, which are considered to be important factors in the healing process. Therefore, researchers have focused on developing methods for preparing biomaterials containing trace elements. A novel method for coating calcium phosphate materials with trace elements is proposed in this study. In this method, mineral components with trace elements were obtained from bone samples and coated onto the titanium surface using only electrical stimulation under constant voltage application in phosphate-buffered saline. The resulting material had poor crystallinity, which was similar to apatite structure present in bone tissue, and it contained trace elements. Calcium phosphate depositions were also constructed on the surfaces of bone and vascular specimens under the same conditions. Consequently, this method can potentially be applied as an innovative treatment for implant surfaces and in the preparation of scaffolds for bone tissue engineering.

Enhancing structural strength and improving cell survival through Polycaprolactone/(gelatin/hydroxyapatite) Core‐Shell nanofibers for tissue engineering

AbstractBone tissue engineering is a practical approach to repairing broken or damaged bones that combines scaffold, cells, and growth factors for treatment. In this study, polycaprolactone (PCL)/gelatin (Ge)/hydroxyapatite (HA) core‐shell nanocomposites have been produced by the coaxial electrospinning method. Coaxial electrospinning is an efficient method for scaffold preparation to provide an interconnected porous fibrous scaffold. The prepared nanocomposite simultaneously benefited from the good mechanical behavior of the core PCL polymer. The desired biological properties also originated from the outer layer of the Ge/HA nanocomposite. Nanofibrous scaffolds' properties were characterized using SEM, TEM, FTIR, TGA, DSC, tensile test, contact angle, and MTT assay. The morphology of the as‐electrospun nanofibers was investigated using SEM and TEM, which revealed a defect‐less fibrous morphology. TEM images showed the core‐shell structure of the prepared scaffold nanofibers. The contact angle test showed that the presence of HA nanoparticles has improved the wettability of fibrous composites. In addition, HA nanoparticles could effectively strengthen the polymer scaffolds. The highest UTS value of 4.1 MPa was obtained in the PCL/(Ge+10%HA) sample. The cytotoxicity results revealed that the prepared scaffolds were utterly biocompatible. Moreover, significant cell proliferation of osteosarcoma cells was observed at high HA contents. The interconnected pores allowed cells to migrate into the scaffolds and grow inside. Based on the obtained results, PCL/(Ge/ HA) core‐shell nanofibers could be a promising candidate for bone scaffolds.

Formation of poly(ε‐caprolactone)‐embedded bioactive nanoparticles/collagen hierarchical scaffolds with the designed and customized porous structures

AbstractThe biodegradable and bioactive bioscaffolds with suitable hierarchical structure, customized shape, and mechanical performance have great potential for biomedical applications especially in tissue engineering field. However, controllable and facile preparation of the related porous scaffolds remains obvious challenge. In this study, poly(ε‐caprolactone) (PCL)‐embedded hydroxyapatite (HAP) nanoparticles/collagen hierarchical scaffolds are facilely prepared basing on 3D printing of the pre‐crosslinked oil in water type Pickering high internal phase emulsion (HIPE) hydrogel. To be specific, in the HAP nanoparticle stabilized Pickering HIPEs, the aqueous phase contains collagen and genipin, and the oil phase is dichloromethane solution of PCL. After the pre‐crosslinking of aqueous phase, the prepared Pickering HIPE turns into emulsion hydrogel with high viscosity and shear thinning characteristics, which can be individually printed and then freeze dried to produce hierarchical scaffolds with the designed structures. The related multiscale pore structures are composed of mm‐scale macropores and μm‐scale micropores, and the related porosity is higher than 84%. Increasing PCL content obviously enhances the compression stress of scaffolds, particularly the compressive stress of porous scaffold prepared with PCL content of 14 w/v% is about 9 times as large as that of porous scaffold without PCL. The results of in vitro mineralization and cell culture assay show that the porous scaffolds have favorable apatite formation ability and biocompatibility. Thus, the prepared hierarchical scaffolds with the designed structures, customized shape and adjustable performance are promising potential applications in bone tissue engineering.

Photocatalyzed Defluorinative Dichloromethylation of α-CF3 Alkenes Using CHCl3 as the Radical Source.

A visible-light-induced defluorinative dichloromethylation of α-CF3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl3 to CDCl3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem-difluoroalkenes.

Methacrylate-Modified Gold Nanoparticles Enable Non-Invasive Monitoring of Photocrosslinked Hydrogel Scaffolds.

Photocrosslinked hydrogels, such as methacrylate-modified gelatin (gelMA) and hyaluronic acid (HAMA), are widely utilized as tissue engineering scaffolds and/or drug delivery vehicles, but lack a suitable means for non-invasive, longitudinal monitoring of surgical placement, biodegradation, and drug release. Therefore, we developed a novel photopolymerizable X-ray contrast agent, methacrylate-modified gold nanoparticles (AuMA NPs), to enable covalent-linking to methacrylate-modified hydrogels (gelMA and HAMA) in one-step during photocrosslinking and non-invasive monitoring by X-ray micro-computed tomography (micro-CT). Hydrogels exhibited a linear increase in X-ray attenuation with increased Au NP concentration to enable quantitative imaging by contrast-enhanced micro-CT. The enzymatic and hydrolytic degradation kinetics of gelMA-Au NP hydrogels were longitudinally monitored by micro-CT for up to one month in vitro, yielding results that were consistent with concurrent measurements by optical spectroscopy and gravimetric analysis. Importantly, AuMA NPs did not disrupt the hydrogel network, rheology, mechanical properties, and hydrolytic stability compared with gelMA alone. GelMA-Au NP hydrogels were thus able to be bioprinted into well-defined three-dimensional architectures supporting endothelial cell viability and growth. Overall, AuMA NPs enabled the preparation of both conventional photopolymerized hydrogels and bioprinted scaffolds with tunable X-ray contrast for noninvasive, longitudinal monitoring of placement, degradation, and NP release by micro-CT.

Polyaniline Functionalized Peptide Self-Assembled Conductive Hydrogel for 3D Cell Culture.

The functionalization of self-assembled peptide hydrogel is of great importance to broaden its applications in the field of biomedicine. In this work, conductive hydrogel is fabricated by introducing conductive polymer polyaniline into peptide self-assembled hydrogel. Compared with pure peptide formed hydrogel, the conductive hydrogel exhibits enhanced conductivity, mechanical property and stability. In addition, the hydrogel is tested to be of great injectability and 3D bio-printability and could support the viability of encapsulated cells that are sensitive to electrical signals. It should have great application prospects in the preparation of tissue engineering scaffolds.

The use of tissue engineering in maxillary sinus augmentation: a review

Tissue engineering is an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function. The most studies are focused on the preparation of scaffolds, selection of the different cell sources and construction of engineered bone. The decrease in bone height in the sinus area after tooth loss is a major challenge in implantology, making the search for new materials a constant challenge. Faced with this, the aim of this review article is to discuss the tissue engineering techniques for maxillary sinus lifting in atrophic jaws.

Additive Manufacturing of Hydroxyapatite Bioceramic Scaffolds with Projection Based 3D Printing

Hydroxyapatite (HA) bioceramics have garnered considerable attention owing to their applications in the field of bone repair and excellent biocompatibility. Compared to extrusion-based 3D printing, projection-based 3D printing (3DPP) can fabricate parts with complex geometry, high accuracy, and efficiency, which is very promising for bioceramic scaffolds. However, conventional 3DPP using a paste with low viscosity will cause severe shrinkage of the parts after sintering, which makes it unsuitable for bioceramic scaffolds, and a system investigation of the printing process remains insufficient. In this study, we proposed a 3DPP device suitable for bioceramic scaffolds and investigated the additive manufacturing of HA scaffolds. Ceramic paste properties and process parameters of curing, debinding, and sintering were initially examined. The mechanical properties, shrinkage, and biocompatibility in vitro of the sintered samples were further investigated. The obtained results indicate that HA bioceramics with uniform morphology, complex structure, and high accuracy can be manufactured using the 3DPP equipment. HA scaffolds have the mechanical strength of human cancellous bone, while HA scaffolds cultured with osteoblast precursor cells possess strong biocompatibility and can promote osteoblast adhesion, proliferation, and differentiation. These results suggest a promising application of the 3DPP technique in the preparation of bioceramic scaffolds, and the HA scaffolds fabricated using the 3DPP technique exhibit promising potential in fulfilling a constructive role in the biomedical field of human bone regeneration repair.

Preparation and properties of ultralight fibrous β-Si3N4 3D scaffolds with honeycomb-like structure by directional freeze-casting

The directional freezing of β-Si3N4 whiskers suspensions followed by high-temperature sintering was employed for fabricating novel highly porous fibrous Si3N4 three-dimensional (3D) scaffolds. A honeycomb-like structure was achieved, in which the directionally aligned lamellar walls were composed of the oriented fibrous Si3N4 grains and bridged by the transverse grains. Ultrahigh porosities ranging from 97.8% to 90.2% and rather low densities from 0.073 to 0.320 g cm−3 could be obtained by controlling the Si3N4 contents from 1.5 to 7.5 vol%. The longitudinal compressive strength was superior to the transverse and increased obviously from 0.19 to 3.7 MPa as the porosity decreased. The superior compressive strength was due to the excellent resistance to bucking-induced elastic instability for the lamellar fibrous Si3N4 walls. Meanwhile, the dielectric constant and loss were decreased to 1.08 and 6.6 × 10−4, respectively. This study provides a strategy for fabricating porous Si3N4 ceramics with ultrahigh porosities and improved strength.

Polyphosphate enhanced biomimetic mineralization of 3D printing scaffolds for bone regeneration

Biomimetic mineralization has been widely applied in the preparation of bone repair materials for achieving better mechanical and biological properties. However, the mineralization effectiveness is not quite satisfactory. Herein, enhanced biomimetic mineralization was realized through polyphosphate modification of gelatin. Molecular dynamics simulations theoretically demonstrated the effectiveness of poly-phosphorylation in augmenting mineralization. Experimental results revealed that poly-phosphorylation could increase the saturation of in-situ mineralization of gelatin from about 25% to more than 40%. Consequently, the compressive strength and elastic modulus of the enhanced mineralized composite were increased by 57.93% and 132.55%, respectively. The osteogenesis was also promoted. Combined with 3D printing, the scaffolds not only had the advantages of enhanced in-situ mineralization but also were endowed with the macro-controllable porous structure to achieve better bone regeneration. It interpreted the mechanism of biomimetic mineralization in terms of the saturation of in-situ mineralization and provided a viable strategy for biomimetic scaffold preparation.

New approach to prepare cytocompatible 3D scaffolds via the combination of sodium hyaluronate and colloidal particles of conductive polymers

Bio-inspired conductive scaffolds composed of sodium hyaluronate containing a colloidal dispersion of water-miscible polyaniline or polypyrrole particles (concentrations of 0.108, 0.054 and 0.036% w/w) were manufactured. For this purpose, either crosslinking with N-(3-dimethylaminopropyl-N-ethylcarbodiimide hydrochloride and N-hydroxysuccinimid or a freeze-thawing process in the presence of poly(vinylalcohol) was used. The scaffolds comprised interconnected pores with prevailing porosity values of ~ 30% and pore sizes enabling the accommodation of cells. A swelling capacity of 92–97% without any sign of disintegration was typical for all samples. The elasticity modulus depended on the composition of the scaffolds, with the highest value of ~ 50 kPa obtained for the sample containing the highest content of polypyrrole particles. The scaffolds did not possess cytotoxicity and allowed cell adhesion and growth on the surface. Using the in vivo-mimicking conditions in a bioreactor, cells were also able to grow into the structure of the scaffolds. The technique of scaffold preparation used here thus overcomes the limitations of conductive polymers (e.g. poor solubility in an aqueous environment, and limited miscibility with other hydrophilic polymer matrices) and moreover leads to the preparation of cytocompatible scaffolds with potentially cell-instructive properties, which may be of advantage in the healing of damaged electro-sensitive tissues.

Galactose Tethered Decellularized Liver Matrix: Toward a Biomimetic and Biofunctional Matrix for Liver Tissue Engineering.

The major challenge in liver tissue engineering is the replication of the microenvironment and microarchitecture of the liver tissue at the nanoscale. Decellularized liver matrix (DLM) provides an ideal material for scaffold preparation, as it retains the relevant structural and biochemical composition. However, the loss of bioactive factors during decellularization needs to be taken into account when using DLM and should be supplemented accordingly for an expected outcome. This study reports on the modification of DLM by the addition of galactose residues using a two-step thiol-ene-mediated photoclick chemistry for the coupling of galactose moieties to the DLM. Modification with galactose enhanced the function of hepatocytes and provides many advantages over currently used DLM and DLM-based materials. The galactose modified DLM enhanced the initial HepG2 cell adhesion to the substrate with changes in dynamics over time such as spheroid formation and further migration on the matrix. Our observation is that the galactose ligand decoration can also enhance the liver-specific metabolism of HepG2 compared to unmodified DLM. Galactosylated DLM also showed a better establishment of cellular polarity which also contributes to the function of HepG2 cells. Together our results demonstrate the advantages of adding galactose residues to currently available biomaterials, which makes this approach an attractive method for ECM-based liver tissue engineering.

Assembly of SBA-15 into hierarchical porous monoliths replicating polymeric scaffolds

This study reports the preparation of highly porous, SBA-15-based monolithic materials with pore sizes spanning over four scales (micro-/meso-/small macro-/large macro-pores). Two approaches were explored. The first one involves the preparation of PMMA scaffolds obtained from chemically-bonded beads and their further infiltration using SBA-15 slurries with suitable viscosity; while the second one directly uses the same amount of PMMA beads dispersed within the slurries. Emphasis was given to the comparison of the textural, structural, and mechanical properties obtained following each approach. Then, application of a thermal consolidation step and its influence over the monoliths properties was investigated, with an optimum observed at 950 °C. The second method systematically allowed reaching higher mechanical resistances (86 vs 32 kPa at 950 °C) for comparable specific surface areas (274 vs 290 m2/g at 950 °C), however at the expense of smaller macropores and lower ordering in the monoliths.

Preparation of a robust silk fibroin scaffold with a reinforced concrete structure constructed with silk nanofibers as the skeleton based on a CaCl2-formic acid solution and freeze-drying method

Regenerated silk fibroin has been widely used in tissue engineering due to its tunable mechanical properties, biocompatibility and degradability, especially in biological scaffolds. In this paper, for the first time, a robust silk fibroin (SF) scaffold with a reinforced concrete structure constructed with silk nanofibers as the skeleton was prepared by combining a CaCl2-formic acid (FA-CaCl2) dissolving system with a freeze-drying method. This method consumes less time and greatly reduces the rate of silk loss, while formic acid can be collected and reused as a solvent during the lyophilization process. Moreover, the SF scaffolds prepared by this method retained the nanofibers of silk, thus preserving the mechanical toughness of the silk nanofibers. On this basis, a reinforced concrete structure with silk nanofibers as the skeleton and amorphous silk as the filler was constructed, which exhibited increased strength and toughness. Effects of preparation conditions (dissolution system, degumming time, silk content) on the mechanical properties and the relationship between structure and mechanical properties of the scaffolds were also studied. Among them, the strength of SF scaffold with degumming time of 10 min, silk content of 20 wt% and directional pores was the best, and its Young's modulus could reach 3.56 MPa. In addition, the scaffolds prepared by this method had good biocompatibility and biodegradability. This study provides a new strategy for manufacturing SF scaffolds and an alternative for the preparation of related silk fibroin materials, which have excellent potential in the field of tissue engineering.

Surface properties and elemental composition of human treated dentin matrix nano-scaffold as direct pulp capping material

Objective The aim of the study was investigating surface topography, roughness, and wettability of the TDM semi-rigid nano-scaffold. In addition to its chemical composition to prove the principle of using as direct pulp capping (DPC) material. Materials and methods: Forty sound and fully erupted premolars scheduled to be extracted for orthodontic treatment were involved for the TDM scaffolds preparation. The surface and chemical properties were investigated in comparison with UTD. The surface topography was investigated using SEM while AFM was used for studying SR. Surface wettability was analyzed via sessile-drop goniometry protocol. However, the elemental composition was analyzed using EDX. Result: The surface characterization of the TDM scaffolds revealed a nano-tubular pattern with high surface wettability. However, the elemental analysis revealed its optimum partial demineralization. Conclusion: the surface and elemental composition of TDM semi-rigid scaffold are promising to be a reasonable DPC material.

Porous scaffold preparation analysis for knee joint using chitosan-polyvinyl alcohol-hydroxyapatite nanoparticles under fuzzy uncertainty

In this research, the purpose is to make a multi-layer porous scaffold with different porosity. The prepared sample has a functionally graded materials (FGM) structure made of chitosan-poly vinyl alcohol (PVA) and various percentages of hydroxyapatite (HA) nanoparticles which are analytically investigated using fuzzy uncertainty. The compressive strength and elastic modulus are measured by mechanical testing and used in the modeling study of Abaqus software. Finally, samples containing the optimum weight percentage of n-HA can be used as a bone substitute for knee joint repair. Many thin components of structures, such as beams, plates, and shells, have thermal changes in thickness. To characterize the samples, scanning electron microscope (SEM) analysis were used for characterization of morphology. These mechanical changes can lead to mechanical deformation, including in-plane components as well as out-of-plane curved components. The obtained results indicate that reducing the mechanical deformation of one component can be achieved using composites whose fibers have a negative longitudinal expansion coefficient. This result is independent of the actual mechanical values within the fixed properties of the components. The beam can also be designed to match or approach an in-plane expansion coefficient or a desired longitudinal stiffness. The size of the pores in the SEM images depict between 100 and 15 μm in the first sample, 150 to 210 μm in the second sample, and 250 to 270 μm in the third sample and suddenly visible with a steady trend in the fourth sample.

Surface Modification of Sponge-like Porous Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/Gelatine Blend Scaffolds for Potential Biomedical Applications.

In this study, we described the preparation of sponge-like porous scaffolds that are feasible for medical applications. A porous structure provides a good microenvironment for cell attachment and proliferation. In this study, a biocompatible PHA, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) was blended with gelatine to improve the copolymer’s hydrophilicity, while structural porosity was introduced into the scaffold via a combination of solvent casting and freeze-drying techniques. Scanning electron microscopy results revealed that the blended scaffolds exhibited higher porosity when the 4HB compositions of P(3HB-co-4HB) ranged from 27 mol% to 50 mol%, but porosity decreased with a high 4HB monomer composition of 82 mol%. The pore size, water absorption capacity, and cell proliferation assay results showed significant improvement after the final weight of blend scaffolds was reduced by half from the initial 0.79 g to 0.4 g. The pore size of 0.79g-(P27mol%G10) increased three-fold while the water absorption capacity of 0.4g-(P50mol%G10) increased to 325%. Meanwhile, the cell proliferation and attachment of 0.4g-(P50mol%G10) and 0.4g-(P82mol%G7.5) increased as compared to the initial seeding number. Based on the overall data obtained, we can conclude that the introduction of a small amount of gelatine into P(3HB-co-4HB) improved the physical and biological properties of blend scaffolds, and the 0.4g-(P50mol%G10) shows great potential for medical applications considering its unique structure and properties.

Characterization of decellularized chicken skin as a tissue engineering scaffold.

Decellularization has been applied to many tissues and organs to obtain biomaterials for applications in tissue engineering. In this study, decellularization and characterization of chicken skin was performed to provide comprehensive information and in-depth details on this material as a potential tissue scaffold. Application of Triton X-100 and sodium dodecyl sulfate (SDS) on tissues at different time intervals as two decellularization protocols were compared according to various aspects, such as removal of cellular components, DNA quantification, protection of extracellular matrix (ECM), mechanical properties, and cytocompatibility, to find the optimum technique during preparation of decellularized scaffolds. The results showed that treatment with SDS revealed better results when compared with Triton X-100 regarding the preservation of tissue structure and morphology, although there was no difference in the efficiency of decellularization. In general, the tissues decellularized with SDS demonstrated higher levels of cytocompatibility and better mechanical properties in comparison with samples treated with Triton X-100. In conclusion, this study revealed that decellularized chicken skin is a cheap, abundant, and biocompatible material that supports cell attachment, growth, and proliferation. Therefore, it could be used as a proper candidate to prepare scaffolds for further studies on tissue engineering, especially for skin tissue engineering.

Cytotoxic effects of chitosan nanoparticles containing Zataria multiflora essential oil against human breast and melanoma cells

BackgroundBreast cancer is the most common cancer among women, and melanoma incidence increases worldwide. The emergence of drug resistance and side effects of chemotherapy drugs has led to a great deal of attention being paid to the development of natural medicines, especially using essential oil. The preparation of essential oil-based nanoformulation has thus recently received more attention.ResultsIn this study, chitosan nanoparticles (ChiNPs) containing Zataria multiflora essential oil with a particle size of 177 ± 10 nm, a narrow particle size distribution (SPAN 0.96), and a cubic-like shape were first prepared. IC50 values of the prepared nanoformulation against human melanoma (A-375) and breast cancer cell lines (MCF-7 and MDA-MB-468) were obtained as 32 (12–84), 46 (32–67), and 105 (85–131) µg/mL. Besides, an electrospun polycaprolactone–polyethylene oxide scaffold was prepared as a dressing after treatment with the nanoformulation. Fourier transform infrared analysis confirmed the scaffold's preparation as well as successful loading of the essential oil in chitosan nanoparticles. Furthermore, the scaffold did not show a cytotoxic effect on A-375, MCF-7, and MDA-MB-468, and its surface was hydrophobic as the water contact angle with the surface was 136.5°.ConclusionsThe prepared prototype with natural ingredients and high efficacy could be considered for further consideration in vivo study or complementary medicine.Graphical abstract

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry.

In the current scenario of medicinal chemistry, quinoline plays a pivotal role in the design of new heterocyclic compounds with several pharmacological properties, so the search for new synthetic methodologies and their application in drug discovery has been widely studied. So far, many procedures have been performed for the preparation of quinoline scaffolds, among which Friedländer quinoline synthesis plays an important role in obtaining these heterocycles. The Friedländer reaction involves condensation between 2-aminobenzaldehydes and keto-compounds. The quinoline nucleus, once obtained through the Friedländer synthesis, has been extensively modified so that these derivatives can exhibit a large number of biological activities such as anticancer, antimalarial, antimicrobial, antifungal, antituberculosis, and antileishmanial properties. In this work, the focus is on the applicability of the Friedländer reaction in the synthesis of various types of bioactive heterocyclic quinoline compounds, which to date has not been reported in the context of medicinal chemistry. The main part of this review selectively focuses on research from 2010 to date and will present highlights of the Friedländer quinoline synthesis procedures and findings to address biological and pharmacological activities.