Scaffolds For Biomedical Applications Research Articles

Porous scaffold hydroxyapatite from sand lobster shells (Panulirus homarus) using polyethylene oxide/chitosan as polymeric porogen for bone tissue engineering.

The hydroxyapatite (HAp; Ca10 (PO4 )6 (OH)2 )) has good biocompatibility, bioactivity, and osteoconductivity as a bone implant because the main inorganic mineral of human bone is HAp. The use of scaffold HAp from biogenic resources that contain high calcium and polymer as a pore forming agent to support bone growth is a longstanding area of interest. In this study, porous scaffolds based on HAp were synthesized from sand lobster (SL; Panulirus homarus) shells as a source of calcium using the porogen leaching method with polyethylene oxide (PEO) and chitosan (Chs) as polymeric porogen. The present study aims to synthesize HAp derived from SL shells and evaluate the effect variations of PEO on the physicochemical properties of the scaffold and cytotoxicity in cell viability assay. Briefly, the SL shell powder was calcinated with temperature variations of 600°C, 800°C, and 1000°C for 6 h. Based on the characterization, it was shown that 1000°C was the optimum calcination temperature for SL shells to synthesize HAp using the precipitation method. The characterization results of HAp using energy dispersive x-ray (EDX) revealed that the molar ratio of Ca/P was 1.67. The Fourier transform infrared (FTIR) and x-ray diffractometer (XRD)spectral patterns indicated that HAp had been successfully synthesized with minor β-tricalcium phosphate (β-TCP), a calcium phosphate with high biocompatibility. Porous scaffolds were synthesized by varying the concentration of PEO at 0, 5, 10, and 15 wt %. Physicochemical analysis revealed that a higher concentration of PEO affected decreased crystallinity and compressive strength, but on the other hand, the porosity and pore sizes increased. Based on the physicochemical analysis, the synthesized porous scaffold showed that HAp/PEO/Chs 15 wt % had the most potential as a scaffold for biomedical applications. MTT Assay, after 24 h incubation, revealed that the scaffold was safe for use at low concentrations on the MC3T3E1 osteoblast cells, with a percentage of cell viability of 83.23 ± 3.18% at 23.4375 μg/mL. Although the cell viability decreased at higher concentrations, the HAp/PEO/Chs 15 wt % scaffold was cytocompatible with the cells. Thus, in the present study, HAp/PEO/Chs 15 wt % was the best scaffold based on pore structure, chemical composition, mechanical and crystalographic properties and cell viability.

Heparin-Loaded Composite Coatings on Porous Stent from Pure Magnesium for Biomedical Applications.

Challenges associated with drug-releasing stents used in percutaneous transluminal coronary angioplasty (PTCA) encompass allergic reactions, prolonged endothelial dysfunction, and delayed stent clotting. Although absorbable stents made from magnesium alloys seem promising, fast in vivo degradation and poor biocompatibility remain major challenges. In this study, zirconia (ZrO2) layers were used as the foundational coat, while calcium phosphate (CaP) served as the surface layer on unalloyed magnesium specimens. Consequently, the corrosion current density was decreased to 3.86, from 13.3 μA/cm2. Moreover, a heparin-controlled release mechanism was created by co-depositing CaP, gelatin (Gel), and heparin (Hep) on the specimens coated with CaP/ZrO2, thereby boosting magnesium's blood compatibility and prolonging the heparin-releasing time. Techniques like X-ray diffractometry (XRD), focused ion beam (FIB) system, toluidine blue testing, UV-visible spectrometry, field emission scanning electron microscopy (FESEM), and surrogate tests for endothelial cell viability were employed to examine the heparin-infused coatings. The drug content rose to 484.19 ± 19.26 μg/cm2 in multi-layered coatings (CaP-Gel-Hep/CaP-Hep/CaP/ZrO2) from 243.56 ± 55.18 μg/cm2 in a single layer (CaP-Hep), with the controlled release spanning beyond 28 days. Also, cellular viability assessments indicated enhanced biocompatibility of the coated samples relative to those without coatings. This suggests the potential of magnesium samples after coating ZrO2 and CaP with Gel as candidates for porous biodegradable stents or even scaffolds in biomedical applications.

Alginate-Based Hydrogels and Scaffolds for Biomedical Applications.

Alginate is a natural polymer of marine origin and, due to its exceptional properties, has great importance as an essential component for the preparation of hydrogels and scaffolds for biomedical applications. The design of biologically interactive hydrogels and scaffolds with advanced, expected and required properties are one of the key issues for successful outcomes in the healing of injured tissues. This review paper presents the multifunctional biomedical applications of alginate-based hydrogels and scaffolds in selected areas, highlighting the key effect of alginate and its influence on the essential properties of the selected biomedical applications. The first part covers scientific achievements for alginate in dermal tissue regeneration, drug delivery systems, cancer treatment, and antimicrobials. The second part is dedicated to our scientific results obtained for the research opus of hydrogel materials for scaffolds based on alginate in synergy with different materials (polymers and bioactive agents). Alginate has proved to be an exceptional polymer for combining with other naturally occurring and synthetic polymers, as well as loading bioactive therapeutic agents to achieve dermal, controlled drug delivery, cancer treatment, and antimicrobial purposes. Our research was based on combinations of alginate with gelatin, 2-hydroxyethyl methacrylate, apatite, graphene oxide and iron(III) oxide, as well as curcumin and resveratrol as bioactive agents. Important features of the prepared scaffolds, such as morphology, porosity, absorption capacity, hydrophilicity, mechanical properties, in vitro degradation, and in vitro and in vivo biocompatibility, have shown favorable properties for the aforementioned applications, and alginate has been an important link in achieving these properties. Alginate, as a component of these systems, proved to be an indispensable factor and played an excellent "role" in the optimal adjustment of the tested properties. This study provides valuable data and information for researchers and demonstrates the importance of the role of alginate as a biomaterial in the design of hydrogels and scaffolds that are powerful medical "tools" for biomedical applications.

Tuning structure in 3D-printed scaffolds of polylactide by extensional stress and its influence on properties

In response to the increasing demand for biological scaffolds for bone defect repair in tissue engineering, fabricating biocompatible porous scaffolds with controllable mechanical properties has been a significant challenge. In this work, we successfully designed a unique Triply Periodic Minimal Surface (TPMS) structure along with delicate uniaxial stretching on it, which was integrated as a “three-dimensional (3D) printing-uniaxial stretching” strategy. The lightweight (0.505 g/cm3) and superior impact strength (25.63 ± 1.4 kJ/m2) of the 3D-printed polylactide (PLA) scaffold are attributed to the smooth and continuous porous structure, which is also beneficial for the uniformly deformed during the uniaxial stretching. With the increase of the draw ratio, the volume proportion of the inner hollow porous progressively expanded, allowing the density to decrease from 0.505 g/cm3 to 0.428 g/cm3 (a decrease of 15.2%). Crucially, the mechanical properties of the 3D-printed porous scaffold are significantly improved after uniaxial stretching. Impact strength and yield strength increased significantly to 400% and 355% of the original 3D-printed PLA scaffold, climbing to 101.16 ± 1.68 kJ/m2 and 13.88 ± 0.68 MPa, respectively. The relative modes of action are discussed in detail. This work provides a novel method to improve the application range of 3D-printed porous scaffolds in biomedical applications of tissue engineering and engineering materials.

Additive manufacturing of bionanomaterials for biomedical applications based on TI6AL4V and PLA: a systematic review

Additive manufacturing (AM) is the owner of a huge potential as a manufacturing technology in fabricating functional implants, and scaffolds for biomedical applications. AM, which includes 3D printing (3DP) and 3D bioprinting, can be the solution to produce several needs such as scaffolds/implants, tissue or organs, or medical devices by combining different biomaterials with nanomaterials. Titanium and its alloys and Polylactic acid (PLA) are commonly used in bone tissue repair with their superior bio-functionality. The rapid advancement of three-dimensional (3D) printing technology has enabled the fabrication of porous titanium and polymer composite scaffolds with controllable microstructures, which is regarded as an effective method for promoting rapid bone repair. An electronic literature search was conducted in PubMed, Web of Science, Scopus, Elsevier, Embase, and other numerous databases up to December 2021 which are accessed by Karabuk university. To evaluate the possibility of bias and methodological quality, the SYRCLE tool and the last version of the CAMARADES list were used, respectively, a meta-analysis could not be performed. This systematic review is aimed to evaluate the common biomedical potential of 3D-printed porous Ti6Al4V (Ti64) and PLA matrix scaffold for repairing bone defects to investigate the influential factors that might affect its osteogenic availability. The most ideal parameters for designing the Ti64 scaffold were found to be a pore size of around 300-400 m and porosity of 60-70%, while PLA scaffolds show 350-400 m and nearly the same percentage in porosity as Ti64.

Cryostructuring of Polymeric Systems: 63. Synthesis of Two Chemically Tanned Gelatin-Based Cryostructurates and Evaluation of Their Potential as Scaffolds for Culturing of Mammalian Cells

Various gelatin-containing gel materials are used as scaffolds for animal and human cell culturing within the fields of cell technologies and tissue engineering. Cryostructuring is a promising technique for the preparation of efficient macroporous scaffolds in biomedical applications. In the current study, two new gelatin-based cryostructurates were synthesized, their physicochemical properties and microstructure were evaluated, and their ability to serve as biocompatible scaffolds for mammalian cells culturing was tested. The preparation procedure included the dissolution of Type A gelatin in water, the addition of urea to inhibit self-gelation, the freezing of such a solution, ice sublimation in vacuo, and urea extraction with ethanol from the freeze-dried matter followed by its cross-linking in an ethanol medium with either carbodiimide or glyoxal. It was shown that in the former case, a denser cross-linked polymer phase was formed, while in the latter case, the macropores in the resultant biopolymer material were wider. The subsequent biotesting of these scaffolds demonstrated their biocompatibility for human mesenchymal stromal cells and HepG2 cells during subcutaneous implantation in rats. Albumin secretion and urea synthesis by HepG2 cells confirmed the possibility of using gelatin cryostructurates for liver tissue engineering.

"Nano, Micro, and Macro Materials in Scaffolds for Biomedical Applications: A Review"

"Nano, Micro, and Macro Materials in Scaffolds for Biomedical Applications: A Review"

Editorial: Electrospinning Based Functional Scaffolds for Biomedical Applications

Editorial: Electrospinning Based Functional Scaffolds for Biomedical Applications

Grapefruit Oil and Cobalt Nitrate-Loaded Polyurethane Hybrid Nanofibrous Scaffold for Biomedical Applications

The goal of this work is to fabricate a new composite based on polyurethane (PU), grapefruit (GP) oil, and cobalt nitrate [Co(NO3)2] using an electrospinning technique. Morphology results revealed the reduction in the fiber diameter of the composites compared to pristine PU control. The interaction of PU with GP and Co(NO3)2 was confirmed by hydrogen bond formation evident in infrared analysis. The fabricated PU/GP composites depicted a more hydrophobic behavior, while PU/GP/Co(NO3)2 showed a hydrophilic behavior than the pristine PU. Atomic force micrographs (AFM) revealed that the developed composites showed a decrease in the surface roughness (Ra) compared to PU. The addition of GP and Co(NO3)2 improved the mechanical strength of the pristine PU. The blood compatibility assays concluded not only the increase in blood clotting levels but also the less toxic nature of the fabricated composites compared to the pristine PU. Hence, the newly designed composites possessing outstanding physicochemical and biological properties may be used as a potential candidate for scaffolding in tissue engineering applications.

Size-Controlled Synthesis of Modifiable Glycine-Terminated Au Nanoclusters as a Platform for Further Functionalization.

An improved and simple synthetic method for producing stable narrow-sized glycine-cystamine (Gly-CSA)-functionalized Au nanoclusters (NCs) from protected Fmoc-glycine-cystamine (Fmoc-Gly-CSA)-functionalized Au NCs is demonstrated in this study. The NC size and size distribution can be controlled directly as a function of reducing agent concentration with the formation of smaller NC core diameters at higher concentrations of NaBH4. Furthermore, when using 0.30 M NaBH4, three UV-vis absorption peaks at 690, 440, and 390 nm were seen, which are consistent with the formation of Fmoc-Gly-CSA-functionalized Au25L18 NCs. After deprotection of the Gly-CSA-functionalized Au NCs, the reactivity of the primary amine groups was investigated. Methyl acrylate-glycine-cystamine (MA-Gly-CSA)-functionalized Au NCs with terminal acetyl groups were formed via the Michael addition reaction of terminal amine groups with methyl acrylate. This reaction resulted in the formation of ester-terminated Au NCs including atom-precise MA-Gly-CSA Au25(SR)18 NCs. The functionalization of the ligand was confirmed by 1H NMR and UV-vis spectra, and TEM images of MA-Gly-CSA- and Gly-CSA-functionalized Au NCs showed that the size of the NCs remained unchanged after the reaction. With controllable NC size and facile functionalization of the Gly-CSA-functionalized Au NCs, these clusters have promising potential as scaffolds for biomedical applications.

Superelasticity, microstructure and texture characteristics of the rapidly solidified Ti–Zr–Nb–Sn shape memory alloy fibers for biomedical applications

The strong 001β<110>β recrystallization texture is known in favor of improving superelastic recovery strain in the biomedical nickel-free Ti–Zr–Nb–Sn shape memory alloys (SMAs) experienced severely cold-rolling followed by annealing. Whereas the severe cold rolling yielded thin ribbon-like sheets which probably have low practical applications for the fabrication of medical devices although they have excellent superelasticity. In this study, Ti–Zr–Nb–Sn SMA fibers with different Nb contents were directly prepared by rapidly solidifying the molten ingot and compared with the referenced alloy sheet in terms of their texture characteristics and superelastic properties. The superelastic SMA fibers have been shown to have a great potential for manufacturing fibrous structure-based plates or scaffolds for biomedical applications. The superelasticity of the rapidly solidified Ti–18Zr‒12.5Nb–2Sn (at.%) SMA fiber specimen was observed in a wide temperature window of 100 °C, ranging from ‒ 65 °C to 35 °C. The increase of 1 at.%‒Nb was first reported to decrease the As and Af of the Ti–Zr–Nb–Sn SMA sheet specimens by 89 °C and 95 °C, respectively. The high-resolution transmission electron microscope (HRTEM) observations revealed that athermal ω phases and nanodomains were formed in the β matrix in the Ti–18Zr‒12.5Nb–2Sn (at.%) SMA fiber specimen. Unlike the referenced bulk sheet showing 001β<110>β recrystallization texture, the rapidly solidified SMA fiber specimen was found to have a main texture close to (334)β[3‾5‾6]β by using electron backscatter diffraction (EBSD). A recovery strain of 5.1% was obtained in the SMA fiber specimen at a pre-strain of 5.5%. The present rapid solidified Ti–Zr–Nb–Sn SMA fibers will be of considerable applications in manufacturing superelastic porous scaffolds for bone repair.

Ice Templating Soft Matter: Fundamental Principles and Fabrication Approaches to Tailor Pore Structure and Morphology and Their Biomedical Applications.

Porous scaffolds are widely used in biomedical applications where pore size and morphology influence a range of biological processes, including mass transfer of solutes, cellular interactions and organization, immune responses, and tissue vascularization, as well as drug delivery from biomaterials. Ice templating, one of the most widely utilized techniques for the fabrication of porous materials, allows control over pore morphology by controlling ice formation in a suspension of solutes. By fine-tuning freezing and solute parameters, ice templating can be used to incorporate pores with tunable morphological features into a wide range of materials using a simple, accessible, and scalable process. While soft matter is widely ice templated for biomedical applications and includes commercial and clinical products, the principles underpinning its ice templating are not reviewed as well as their inorganic counterparts. This review describes and critically evaluates fundamental principles, fabrication and characterization approaches, and biomedical applications of ice templating in polymer-based biomaterials. It describes the utility of porous scaffolds in biomedical applications, highlighting biological mechanisms impacted by pore features, outlines the physical and thermodynamic mechanisms underpinning ice templating, describes common fabrication setups, critically evaluates complexities of ice templating specific to polymers, and discusses future directions in this field.

Novel three‐dimensional printing of poly(ester urethane) scaffolds for biomedical applications

AbstractTissue engineering requires highly porous complex structures with interconnected pores and tightly controlled pore sizes, added to customized production. Additive manufacturing (AM) is nowadays one of the most suitable technologies for the preparation of structures with strictly defined complex three‐dimensional architectures. Moreover, computed tomography and magnetic resonance imaging can be employed to obtain personalized medical devices. Fused deposition modeling (FDM) is one of the most common, easiest, and cost‐effective AM techniques to obtain 3D objects from a wide variety of materials. However, there is a lack of bioresorbable materials that can fit the increasing demand for biomedical applications requiring stiff elastomers. In this work, a series of bioresorbable segmented poly(ester urethanes) (SPEU) with high hard segment content was synthesized and physicochemically characterized. The materials with higher thermal stability were processed into homogeneous filaments by hot‐melt extrusion with no need for additives nor plasticizers. These filaments were evaluated for FDM, and structures with controlled porosity, filament diameter, and in‐plane pore size could be easily obtained by modifying the printing parameters. Regarding SPEU mechanical properties, the obtained scaffolds could be promising for cartilage tissue engineering applications.

On shear resistance of almond skin reinforced PLA composite matrix-based scaffold using cancellous screw

ABSTRACT The polylactic acid (PLA) matrix is being widely used as a scaffold for biomedical applications. But hitherto little has been reported on the use of 3D printed almond skin (AS) powder-reinforced matrix of PLA as a scaffold for ensuring shear resistance properties at different insertion angle, depth and infill pattern for holding a cancellous screw. This paper reports the shear fracture and morphological features of the 3D printed AS powder-reinforced matrix of PLA, prepared by fused deposition modelling for biomedical scaffolds using a cancellous pedicle screw. The study was performed using the angle of insertion 10°, 20° and 30°, depth of insertion of screw 40%, 70% and 100% in prototype and infill patterns (honeycomb, rectilinear and triangular) of 3D printed functional prototype. The study suggested that the maximum shear strength at peak (23.02 MPa) and maximum shear strength at break (22.90 MPa) were observed for honeycomb printing infill pattern, 100% insertion of screw and at 30° angle of insertion to prototype, whereas maximum modulus of toughness was observed for rectilinear pattern with 100% insertion of screw and 20° angle of insertion. Further morphological study was performed on the fractured surface to support the mechanical results obtained by pull-out test for ensuring shear resistance. Overall the study will be useful for an orthopaedic surgeon for ensuring angle, depth of insertion and infill pattern selection for minimising the shear fracture of the scaffold.

Preparation of protein nanoparticle-coated poly(hydroxybutyrate) electrospun nanofiber based scaffold for biomedical applications

In this study, soybean protein nanoparticles (SPN) modified poly(hydroxybutyrate) (PHB) electrospun nanofiber scaffold is fabricated by a facile two-step method combination of PHB electrospinning and SPN evaporation-induced self-assembly. The surface characteristics, structure and properties are investigated by SEM, EDS, XPS, FTIR, XRD, DMA, WCA, tensile test and water uptake capacity measurements. To characterize biodegradability and cytocompatibility, biodegradation tests are performed in simulated body fluid with and without lysozyme and cell cultures are carried out using NIH3T3 mouse fibroblast cells by in vitro studies. The as-obtained SPN-modified PHB nanofiber scaffold presents better cytocompatibility and is more suitable for biomedical applications.

Poly(lactic acid) and its composites as functional materials for 3-D scaffolds in biomedical applications: A mini review of recent trends

Poly(lactic acid) and its composites as functional materials for 3-D scaffolds in biomedical applications: A mini review of recent trends

Fabrication of three-dimensional PCL/BiFeO3 scaffolds for biomedical applications

The aim of this study is to examine the pH effect on bismuth ferrite (BiFeO3) properties and observe the BiFeO3 behaviour in the polycaprolactone (PCL). In this paper, BiFeO3 was synthesized via co-precipitation method at three different pH values (10.64, 11.32, and 11.58). These produced particles were added into the 25wt.%PCL solutions separately to get the scaffolds using a 3D printing process. Crystallite sizes were determined from the Debye-Scherer formula using XRD. With different pH values, crystal sizes were found as 15, 12, and 10 nm and particle sizes determined from SEM were 142, 134, and 111.39 nm for 10.64, 11.32, and 11.58, respectively. The adenocarcinoma lung cancer cell (A549) adhesion on the scaffolds revealed that cells could attach to the scaffolds. Maximum dielectric constant values were obtained for the pellets and scaffolds as 10.37 nF and 6.16 nF for the pellet BiFeO3 (pH = 11.58) and the scaffold 25wt.%PCL/2wt.%BiFeO3 (pH = 11.58), respectively.

Design of Novel Perovskite-Based Polymeric Poly(l-Lactide-Co-Glycolide) Nanofibers with Anti-Microbial Properties for Tissue Engineering.

There is a growing need for anti-microbial materials in several biomedical application areas, such are hernia, skin grafts as well as gynecological products, owing to the complications caused by infection due to surgical biomaterials. The anti-microbial effects of silver in the form of nanoparticles, although effective, can be toxic to surrounding cells. In this study, we report, for the first time, a novel biomedical application of Ag0.3Na1.7La2Ti3O10-layered perovskite particles, blended with poly(L-lactide-co-glycolide) (PLGA), aimed at designing anti-microbial and tissue engineering scaffolds. The perovskite was incorporated in three concentrations of 1, 5, 10 and 15 w/w% and electrospun using dimethylformamide (DMF) and chloroform. The morphology of the resultant nanofibers revealed fiber diameters in the range of 408 to 610 nm by scanning electron microscopy. Mechanical properties of perovskite-based nanofibers also matched similar mechanical properties to human skin. We observed impressive anti-microbial activity, against Gram-negative, Gram-positive bacteria and even fungi, to Ag0.3Na1.7La2Ti3O10 in powder as well as nanofiber-incorporated forms. Furthermore, cytotoxicity assay and immunocytochemistry revealed that perovskite-based nanofibers promoted the proliferation of human dermal fibroblasts whist maintaining normal cellular protein expression. Our study shows that perovskite-nanofibers have potential as scaffolds for biomedical applications with anti-microbial needs.

Amphipathic Substrates Based on Crosslinker-Free Poly(ε-Caprolactone):Poly(2-Hydroxyethyl Methacrylate) Semi-Interpenetrated Networks Promote Serum Protein Adsorption.

A simple procedure has been developed to synthesize uncrosslinked soluble poly(hydroxyethyl methacrylate) (PHEMA) gels, ready for use in a subsequent fabrication stage. The presence of 75 wt % methanol (MetOH) or dimethylformamide (DMF) impedes lateral hydroxyl–hydroxyl hydrogen bonds between PHEMA macromers to form during their solution polymerization at 60 °C, up to 24 h. These gels remain soluble when properly stored in closed containers under cold conditions and, when needed, yield by solvent evaporation spontaneous physically-crosslinked PHEMA adapted to the mould used. Moreover, this two-step procedure allows obtaining multicomponent systems where a stable and water-affine PHEMA network would be of interest. In particular, amphiphilic polycaprolactone (PCL):PHEMA semi-interpenetrated (sIPN) substrates have been developed, from quaternary metastable solutions in chloroform (CHCl3):MetOH 3:1 wt. and PCL ranging from 50 to 90 wt % in the polymer fraction (thus determining the composition of the solution). The coexistence of these countered molecules, uniformly distributed at the nanoscale, has proven to enhance the number and interactions of serum protein adsorbed from the acellular medium as compared to the homopolymers, the sIPN containing 80 wt % PCL showing an outstanding development. In accordance to the quaternary diagram presented, this protocol can be adapted for the development of polymer substrates, coatings or scaffolds for biomedical applications, not relying upon phase separation, such as the electrospun mats here proposed herein (12 wt % polymer solutions were used for this purpose, with PCL ranging from 50% to 100% in the polymer fraction).

Introduction of Hydrogen Bonds Improves the Shape Fidelity of Viscoelastic 3D Printed Scaffolds While Maintaining Their Low-Temperature Printability

In spite of the rapid adoption of three-dimensional (3D) printed scaffolds in biomedical applications, there is a paucity of low-modulus 3D printable biodegradable polymers available for fabricatio...