Potential Biomedical Materials Research Articles

A TA/Cu2+ Nanoparticle Enhanced Carboxymethyl Chitosan-Based Hydrogel Dressing with Antioxidant Properties and Promoting Wound Healing.

As the first line of immune defense and the largest organ of body, skin is vulnerable to damage caused by surgery, burns, collisions and other factors. Wound healing in the skin is a long and complex physiological process that is influenced by a number of different factors. Proper wound care can greatly improve the speed of wound healing and reduce the generation of scars. However, traditional wound dressings (bandages, gauze, etc.) often used in clinical practice have a single function, lack of active ingredients and are limited in use. Hydrogels with three-dimensional network structure are a potential biomedical material because of their physical and chemical environment similar to extracellular matrix. In particular, hydrogel dressings with low price, good biocompatibility, degradability, antibacterial and angiogenic activity are favored by the public. Here, a carboxymethyl chitosan-based hydrogel dressing (CMCS-TA/Cu2+) reinforced by copper ion crosslinked tannic acid (TA/Cu2+) nanoparticles was developed. This study investigated the physical and chemical characteristics, cytotoxicity, and angiogenesis of TA/Cu2+ nanoparticles and CMCS-TA/Cu2+ hydrogels. Furthermore, a full-thickness skin defect wound model was employed to assess the in vivo wound healing capacity of hydrogel dressings. The introduction of TA/Cu2+ nanoparticles not only could increase the mechanical properties of the hydrogel but also continuously releases copper ions to promote cell migration (the cell migration could reach 92% at 48 h) and tubule formation, remove free radicals and promote wound healing (repair rate could reach 90% at 9 days). Experiments have proved that CMCS-TA/Cu2+ hydrogel has good cytocompatibility, antioxidant and wound healing ability, providing an advantageous solution for skin repair.

Synthesis of titanium carbide coating on Ti15Mo alloy and its tribological behaviour

AbstractTi15Mo alloy has been regarded as one of the most potential biomedical materials due to its excellent performance. However, the low hardness and poor wear resistance of titanium alloy limit the further application. Therefore, high temperature solid carburising technology was performed on the surface of Ti15Mo alloys to prepare titanium carbide (TiC) coating with graphene (G) as the carburising agent. The microstructure, mechanical properties, and tribological properties of TiC coating under different lubricants were investigated. Results showed that TiC coating was closely bonded to the titanium substrate. The maximum thickness of TiC coating treated with 1150°C was approximately 184.02 μm, and the microhardness of alloys treated with 1100°C can achieve 1221.5 HV. All modified Ti15Mo alloys showed improved tribological performance compared to the original samples. The wear mechanisms of modified Ti15Mo alloys were abrasive wear and adhesive wear under the SBF lubricant, and the TiC coating was slightly peeled off. The overall friction coefficient and wear rate under 25% calf serum lubricant were lower than the SBF lubricant, and surface scratches were almost absent, and slight abrasive wear and adhesive wear occurred on the surface.

A bioinspired synthetic fused protein adhesive from barnacle cement and spider dragline for potential biomedical materials

Biomaterials with excellent biocompatibility, mechanical performance, and self-recovery properties are urgently needed for tissue regeneration. Inspired by barnacle cement and spider silk, we genetically designed and overexpressed a fused protein (cp19k-MaSp1) composed of Megabalanus rosa (cp19k) and Nephila clavata dragline silk protein (MaSp1) in Pichia pastoris. The recombinant cp19k-MaSp1 exhibited enhanced adhesion capability beyond those of the individual proteins in both aqueous and non-aqueous conditions. cp19k-MaSp1 protein fiber scaffolds prepared through electrospinning have adequate hydrophilicity compared to cp19k and MaSp1 protein fiber scaffolds, and offer improved overall porosity compared to MaSp1 protein fiber scaffolds. The cp19k-MaSp1 protein fiber scaffolds showed excellent proteolytically stable properties because of only 9.6 % depletion after incubation in a biodegradation solution for 56 d. The cp19k-MaSp1 protein fiber scaffolds present remarkably high extreme tensile strength (112.7 ± 11.6 MPa) and superior ductility (438.4 ± 43.9 %) compared with cp19k (34.4 ± 8.1 MPa, 115.4 ± 32.7 %) and MaSp1 protein fiber scaffolds (65.8 ± 9.3 MPa, 409.6 ± 23.1 %), also 68.4 % of tensile strength was recovered by incubation in K+ buffer after multiple stretches, which create a favorable cell adhesion, growth, and proliferation environment for human umbilical vein endothelial cells (HUVECs). The improved biocompatibility, extensive adhesion, mechanical strength, and self-recovery properties make the bioinspired synthetic cp19k-MaSp1 a potential candidate for biomedical tissue reconstruction.

Controllable release of nitric oxide from an injectable alginate hydrogel

Currently, the controlled release of nitric oxide (NO) plays a crucial role in various biomedical applications. However, injectable NO-releasing materials remain an underexplored research field to date. In this study, via the incorporation of S-nitroso-N-acetyl-penicillamine (SNAP) as an NO donor, a family of NO-releasing injectable hydrogels was synthesized through the in situ cross-linking between sodium alginate and calcium ion induced by D-(+)-gluconate δ-lactone as an initiator. Initially, the organic functional groups and the corresponding morphologies of the resulting injectable hydrogels were characterized by IR and SEM spectroscopies, respectively. The NO release times of hydrogels with different SNAP loading amounts could reach up to 36–47 h. Due to the release of NO, the highest antibacterial rates of these injectable hydrogels against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were up to 95 %, respectively. Furthermore, the matrix of these hydrogels demonstrated great water absorption ability, swelling behavior, and degradation performance. Finally, we expect that these NO-releasing injectable hydrogels could have great potential applications various biomedical material fields.

Antibacterial piperazine‐derived quaternized copolyesters with controlled degradability

AbstractThe slow degradability of aliphatic polyesters can be attributed to their poor hydrophilicity. In this article, we report on a series of biodegradable and biocompatible pH‐responsive piperazine‐based copolyesters labeled P2‐P7 synthesized by melt polycondensation approach that exhibit tunable hydrophilicity with antibacterial properties. X‐ray diffraction analysis showed the copolymers to be highly crystalline, with their crystallinity in the range of 41%–55%. Contact angle measurements showed moderate hydrophilicity, with a water contact angle of 59°–71° for P2‐P7 suggesting that the incorporation of piperazine units in the copolymer backbone moderately improves their hydrophilicity. N‐alkylation with methyl iodide further enhanced their hydrophilicity with their measured contact angles changing from 62° in unalkylated P2 to 27° in the fully alkylated analogue P12. The effect of crystallinity and hydrophilicity on polyester degradation was systematically investigated by hydrolytic degradation studies. The quaternized copolymer P10 showed ~39% reduction in molecular weight, whereas only ~19% of P2 was degraded in 8 weeks, thus exhibiting faster degradation in the quaternized polyester. The biocompatibility with U2OS cells and the antibacterial properties established their importance as potential biomedical materials.

A keratin/chitosan sponge with excellent hemostatic performance for uncontrolled bleeding

Uncontrolled bleeding leads to a higher fatality rate in the situation of surgery, traffic accidents and warfare. Traditional hemostatic materials such as bandages are not ideal for uncontrolled or incompressible bleeding. Therefore, it is of great significance to develop a new medical biomaterial with excellent rapid hemostatic effect. Keratin is a natural, biocompatible and biodegradable protein which contains amino acid sequences that induce cell adhesion. As a potential biomedical material, keratin has been developed and paid attention in tissue engineering fields such as promoting wound healing and nerve repair. Herein, a keratin/chitosan (K/C) sponge was prepared to achieve rapid hemostasis. The characterizations of K/C sponge were investigated, including SEM, TGA, liquid absorption and porosity, showing that the high porosity up to 90.12 ± 2.17 % resulted in an excellent blood absorption. The cytotoxicity test and implantation experiment proved that the K/C sponge was biocompatible and biodegradable. Moreover, the prepared K/C sponge showed better hemostatic performance than chitosan sponge (CS) and the commercially available gelatin sponge in both rat tail amputation and liver trauma bleeding models. Further experiments showed that K/C sponge plays a hemostatic role through the endogenous coagulation pathway, thus shortening the activated partial thromboplastin time (APTT) effectively. Therefore, this study provided a K/C sponge which can be served as a promising biomedical hemostatic material.

ULTRA-PRECISION DIAMOND PROCESSING OF BIODEGRADABLE AZ31 ALLOY FOR ORTHOPEDIC APPLICATION

The biodegradable magnesium (Mg) alloys have been acknowledged amongst the top potential biomedical materials for developing different orthopedic devices. Indeed, the processed Mg alloys’ surface integrity shows a substantial contribution to the resulting biomedical applications’ performance. In this paper, the effect of various influential process parameters of an ultra-precision diamond turning (UPDT), such as rotational frequency of spindle, tool overhanging (TOH), feed rate (FR), and depth-of-cut (DOC) on the chip formation, shearing mechanism, and surface finish of the biodegradable Mg AZ31 alloy have been studied. The resulting chips’ analysis of the different processing parameters has been studied to investigate the involved shearing mechanism. Besides, a relationship between the resulting surface topography and the consequences of UPDT-parameters on skewness ([Formula: see text]) and kurtosis ([Formula: see text]) was studied. The statistical analysis highlighted that the FR and TOH significantly influenced the surface roughness of the Mg AZ31 alloys at a 95% confidence level. Therefore, being statistically dominating, the morphology of the formed chip has also been influenced by FR and TOH’s parametric levels. The UPDT-processed Mg-alloy possessed a nano-finished surface that acted as hydrophobic and could prevent the surface from corrosion. In the light of experimental findings, the UPDT-processed Mg-alloy can be used for orthopedic screws and plates applications.

Cellulose‐Based Biomaterials: Chemistry and Biomedical Applications

AbstractThis review represents a fresh survey about cellulose‐based biomaterial for biomedical application, in which certain features that are essential to design potential biomedical materials. It illustrates their functionalizations, benefits, properties, and applications in the biomedical. Cellulose is produced from plants and alternative sources such as bacteria, algae, and fungi as well as animals where tunicate is the only animal source of cellulose. Biomedical materials based on cellulose attracts attention due to its unique physicochemical features and high biocompatibility. Thus, cellulose‐based biomaterials have wide potential to be used in large scale biomedical applications as a pioneering material that may be used alone or with other additives. Additionally, they are used in several biomedical applications such as drug delivery, wound dressing, and tissue engineering. However, cellulose is not extensively used in the biomedical industrial field, this may be due to the limitations of the full studies and the limitation of availability of clinical trials. Moreover, the biomaterials based on cellulose are a potential substrate for the 3D bioprinting field where the tissues and organs can be designed as prototype production. For all these reasons, this work will highlight the recent developments in the preparation methods of cellulose‐based biomaterials and their derivatives.

Scale-Up Studies for Polyhydroxyalkanoate and Halocin Production by <i>Halomonas</i> Sp. as Potential Biomedical Materials

Polyhydroxyalkanoates (PHA) are the biomaterials isolated naturally from bacterial strains. These are present in granules and accumulated intracellularly for storage and energy uptake in stressed conditions. This work was based on the extraction of polyhydroxyalkanoates from haloarchaeal strains isolated from samples of a salt mine and Halocin activity screening of these isolates. For the screening of polyhydroxyalkanoates, Nile Blue and Sudan Black Staining were performed. After confirmation and theoretical determination, polyhydroxyalkanoates extraction was done by sodium hypochlorite digestion and solvent extraction by chloroform method in combination. Polyhydroxyalkanoates production was calculated along with the determination of biomass. Halocin activity of these strains was also screened at different intervals. Isolated strains were identified by 16S RNA gene sequencing. Polyhydroxyalkanoates polymer was produced in form of biofilms and brittle crystals. Halocin activity was exhibited by four strains, among which confirmed halocin activity was shown by strain K7. The remarkable results showed that polyhydroxyalkanoates can replace synthetic plastics which are not environment friendly as they cause environmental pollution – a major threat to Earth rising gradually. Therefore, by switching to the use of biodegradable bioplastics from the use of synthetic plastics, it would be beneficial to the ecosphere.

New Ti-Fe-Sn-Y alloys designed for laser direct energy deposition

To develop potential biomedical materials for laser direct energy deposition, five Ti-Fe-Sn-Y alloys with varying Sn contents were designed using a dual cluster model. Systemic investigation for microstructure and properties of the alloys fabricated by laser additive manufacturing were then performed. The results show that the microstructure of as-deposited alloys evolves from diphasic hypereutectic-structure to triphasic hypoeutectic-structure with the increase of Sn addition. As a result, the hardness, strength, ductility, and Young's modulus of the as-deposited alloys gradually decrease in the whole, whereas tribological properties increase with the increase of Sn addition to 4.42 at.%, and decrease afterwards. Moreover, all as-deposited alloys do not present any cytotoxic effect. These results suggest that the near-eutectic alloy with 4.42 at.% Sn has the optimum combination of mechanical, chemical, tribological, and forming properties, being a promising candidate as L-DED biological implant material.

PCL nanofibrous incorporating unique matrix fusion protein adsorbed mesoporous bioactive glass for bone tissue engineering

Mesoporous bioactive glass (MBG) is a potential biomedical material in bone defect repairment because of its bioactivity, biocompatibility, and osteoinduction properties. Here we report that Mg-doped MBG scaffold with 3:1 Ca/Mg ratio (MBG-Ca/Mg-3) is good for MC3T3-E1 osteoblast differentiation and mineralization. Mimicking bone extracellular matrix structure by electrospinning, we used MBG-Ca/Mg-3 adsorbed with Osteocalcin-Osteopontin-Biglycan (OOB), a new unique matrix fusion protein, to form OOB@MBG-Ca/Mg-3 scaffold, which has multifunctional ability in calvarial bone defect repairment in vivo. Intriguingly, we found that OOB@MBG-Ca/Mg-3 scaffold increases the expression of osteoblastic marker genes, including bone morphogenetic protein (Bmp2), osteopontin (Opn), Osterix, Runx2 through activation of ERK1/2. We concluded that OOB@MBG-Ca/Mg-3 scaffold promotes osteoblast differentiation and mineralization through ERK1/2 pathway and it can also enhance bone formation in vivo, which provides a new biomaterial in bone tissue engineering.

Biocompatibility of NbTaTiVZr with Surface Modifications for Osteoblasts.

We report a potential biomedical material, NbTaTiVZr, and the impact of surface roughness on the osteoblast culture and later behavior based on in vitro tests of preosteoblasts. Cell activities such as adhesion, viability, and typical protein activity on NbTaTiVZr showed comparable results with that of commercially pure Ti (CP-Ti). In addition, NbTaTiVZr with a smooth surface exhibits better cell adhesion, viability, and typical protein activity which shows that surface modification can improve the biocompatibility of NbTaTiVZr. This supports the biological evidence and shows that NbTaTiVZr can potentially be evaluated as a biomedical material for clinical use.

Effect of introduction of B2O3 instead of TiO2 on Physico-chemical properties and bioactivity of phosphate-based glasses

This paper studies the in vitro behavior of borophosphate glasses, which are considered potential biomedical materials. To this end, five glass compositions in the system 30Na2O-20CaO-xB2O3-(20-x)TiO2-30P2O5 with 0 ≤ x ≤ 20 have been elaborated by the conventional melt-quenching technic. As expected, replacing TiO2 by B2O3 in the phosphate glasses decreased remarkably the glass transition, crystallization and melting temperatures (Tg, Tc and Tm). The density (ρ) decreased, while VM increased with increasing B2O3 suggesting the reduce in strength of the glasses. Infrared spectroscopy revealed that the glassy network contained PO3, PO4, BO3 and BO4 units with P-O-L (L = P, Ti and B), Ti-O and B-O-B linkages. Moreover, in vitro bioactive behavior was investigated using SBF solution for the glass composition × = 15 mol %, XRD and Infrared spectroscopy were used to characterize the changes that occurred in glasses surface.

Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis

Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.

Microgalvanic Corrosion of Mg-Ca and Mg-Al-Ca Alloys in NaCl and Na2SO4 Solutions.

As a kind of potential biomedical material, Mg–Ca alloy has attracted much attention. However, the role of Ca-containing intermetallics in microgalvanic corrosion is still controversial. In 0.6 mol/L NaCl and Na2SO4 solutions, the microgalvanic corrosion behavior of the second phase and Mg matrix of Mg–Ca and Mg–Al–Ca alloys was examined. It was confirmed that the Mg2Ca phase acts as a microanode in microgalvanic corrosion in both NaCl and Na2SO4 solutions, with the Mg matrix acting as the cathode and the Al2Ca phase acting as the microcathode to accelerate corrosion of the adjacent Mg matrix. It was also found that Cl− and SO42− have different sensibilities to microgalvanic corrosion.

Fabricating Honeycomb Titanium by Freeze Casting and Anodizing for Biomedical Applications

Herein, porous titanium materials with honeycomb pore structure are prepared by freeze casting. The effect of freezing temperature on the pore structure and mechanical properties is also investigated. As the freezing temperature decreases from −10 to −50 °C, the compressive strength decreases from 79.5 ± 9.2 to 55.0 ± 4.3 MPa, and then increases to 90.1 ± 4.4 MPa. Porous titanium with an average pore size of 111.3 ± 25.2 μm and porosity over 60% are obtained at −10 °C. And the porous titanium is observed to form a neatly arranged nanopore structure with an average pore size of 28.5 ± 2.8 nm on the surface after anodizing. These nanopore structures can promote MG‐63 cell adhesion and proliferation, thus improving the biocompatibility of porous titanium. Further, in the simulated body fluid culture experiment, culturing for 3 days can induce Ca2+ and PO43− to nucleate and deposit on the surface of anodized porous titanium, while 7 days can deposit a lot of apatite on the surface. In contrast, no apatite deposition is observed on the surface of the porous titanium sample without anodizing. These prepared porous titanium materials with high porosity, large pore size, sufficient mechanical properties, good biocompatibility, and biological activity might be a potential biomedical material.

Fused filament fabrication of biodegradable polylactic acid reinforced by nanoclay as a potential biomedical material

Fused filament fabrication (FFF) is one of the most common 3D printing techniques having considerable potential in various fields such as pharmaceutical, medical, aerospace, and automotive. One of the impediments of FFF components is their lower mechanical performance compared with those from conventional fabrication methods. This work aims to investigate the effect of adding nanoclay due to being nontoxic to the biodegradable polylactic acid (PLA) polymer matrix for medical applications. PLA granules were melt-compounded by a twin-screw extruder with nanoclay at 2 and 4 wt.%, and then, PLA and PLA/nanoclay filaments were produced using a single-screw extruder. An L9 orthogonal array of the Taguchi approach was utilized as the design of the experiment tool to study the process in detail considering nanoclay content, nozzle temperature and raster angle as material and processing parameters. The dispersion of nanoclay in the PLA matrix was assessed by X-ray diffraction test. The results indicated that the tensile strength was enhanced by 4.6% and 15.3% using the addition of 2 and 4 wt.% of nanoclay, respectively. The microscopic observations showed that the bonding between the rasters and between the contours and rasters was improved by increasing the temperature, and consequently, led to higher tensile strength values. The results revealed that the tensile strength of 38.9 MPa was obtained at the optimum condition.

Influence of MXene Particles with a Stacked-Lamellar Structure on Osteogenic Differentiation of Human Mesenchymal Stem Cells.

MXenes with a two-dimensional (2D) structure have attracted attention as potential biomedical materials. In this study, Ti3C2 MXene particles with 2D-lamellar structures were intercalated and their potential as a biomaterial was evaluated using human mesenchymal stem cells. Intercalated MXene was characterized in terms of microstructure, phase composition, and size. Cell proliferation experiments with MXene particles confirmed that concentrations >50 μg/mL were cytotoxic, while concentrations <20 μg/mL promoted osteogenic differentiation. Moreover, MXene effectively facilitated the early and late osteogenic gene expression.

Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine.

γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid, or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible, non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally friendly biological material. The review concentrates on the reports revealing the functions and potential use of γ-PGA and its derivatives in medicine. γ-PGA is described to possess several properties that may be exploited in medicine. The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/ deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and contrast agent. γ-PGA could be potentially considered as a potential biomedical material in the field of medicine.

Effect of Shape on the Entering of Graphene Quantum Dots into a Membrane: A Molecular Dynamics Simulation.

Graphene quantum dots (GQDs), a new quasi-zero-dimensional nanomaterial, have the advantages of a smaller transverse size, better biocompatibility, and lower toxicity. They have potential applications in biosensors, drug delivery, and biological imaging. Therefore, it is particularly important to understand the transport mechanism of the GQDs on the cell membrane. In particular, the effect of the GQD shapes on the translocation mechanism should be well understood. In this study, the permeation process of the GQDs with different shapes through a 1-palmitoyl-2-oleoylphosphatidylcholine membrane was studied using molecular dynamics. The results show that all small-sized GQDs with different shapes translocated through the lipid membrane at a nanosecond timescale. The GQDs tend to remain on the surface of the cell membrane; then, the corners of the GQDs spontaneously enter the cell membrane; and, finally, the entire GQDs enter the cell membrane and tend to stabilize in the middle of the cell membrane. Moreover, the GQDs do not induce notable damage to the cell membrane, indicating that they are less toxic to cells and can be used as a potential biomedical material.