Tetramethylpyrazine-loaded electroconductive hydrogels promote tissue repair after spinal cord injury by protecting the blood-spinal cord barrier and neurons.

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI. However, its therapeutic potential is hindered by challenges in the administration route and suboptimal bioavailability, leading to attenuated clinical outcomes. To address this challenge, traditional Chinese medicine, TMP, was used in this study to construct a drug-loaded electroconductive hydrogel for synergistic treatment of SCI. A conductive hydrogel combined with TMP demonstrates good electrical and mechanical properties as well as superior biocompatibility. Furthermore, it also facilitates sustained local release of TMP at the implantation site. Furthermore, the TMP-loaded electroconductive hydrogel could suppress oxidative stress responses, thereby diminishing endothelial cell apoptosis and the breakdown of tight junction proteins. This concerted action repairs BSCB integrity. Concurrently, myelin-associated axons and neurons are protected against death, which meaningfully restore neurological functions post spinal cord injury. Hence, these findings indicate that combining the electroconductive hydrogel with TMP presents a promising avenue for potentiating drug efficacy and synergistic repair following SCI.

Sandwich hydrogel to realize cartilage-mimetic structures and performances from polyvinyl alcohol, chitosan and sodium hyaluronate.

Developing artificial substitutes that mimic the structures and performances of natural cartilage is of great importance. However, it is challenging to integrate the high strength, excellent biocompatibility, low coefficient of friction, long-term wear resistance, outstanding swelling resistance, and osseointegration potential into one material. Herein, a sandwich hydrogel with cartilage-mimetic structures and performances was prepared to achieve this goal. The precursor hydrogel was obtained by freezing-thawing the mixture of poly vinyl alcohol, chitosan and deionized water three cycles, accompanied by soaking in sodium hyaluronate solution. The top of the precursor hydrogel was hydrophobically modified with lauroyl chloride and then loaded with lecithin, while the bottom was mineralized with hydroxyapatite. Due to the multiple linkages (crystalline domains, hydrogen bonds, and ionic interactions), the compressive stress was 71 MPa. Owing to the synergy of the hydrophobic modification and lecithin, the coefficient of friction was 0.01. Additionally, no wear trace was observed after 50,000 wear cycles. Remarkably, hydroxyapatite enabled the hydrogel osseointegration potential. The swelling ratio of the hydrogel was 0.06 g/g after soaking in simulated synovial fluid for 7 days. Since raw materials were non-toxic, the cell viability was 100 %. All of the above merits make it an ideal material for cartilage replacement.

Using osteogenic medium in the in vitro evaluation of bone biomaterials: Artefacts due to a synergistic effect.

In vitro tests using bone cells to evaluate the osteogenic potential of biomaterials usually employ the osteogenic medium (OM). The lack of correlation frequently reported between in vitro and in vivo studies in bone biomaterials, makes necessary the evaluation of the impact of osteogenic supplements on these results. This study analysed the proteomic profiles of human osteoblasts (HOb) cultured in the media with and without osteogenic agents (ascorbic acid and ß-glycerol phosphate). The cells were incubated for 1 and 7 days, on their own or in contact with Ti. The comparative Perseus analysis identified 2544 proteins whose expression was affected by osteogenic agents. We observed that the OM strongly alters protein expression profiles with a complex impact on multiple pathways associated with adhesion, immunity, oxidative stress, coagulation, angiogenesis and osteogenesis. OM-triggered changes in the HOb intracellular energy production mechanisms, with key roles in osteoblast maturation. HOb cultured with and without Ti showed enrichment in the skeletal system development function due to the OM. However, differentially expressed proteins with key regenerative functions were associated with a synergistic effect of OM and Ti. This synergy, caused by the Ti-OM interaction, could complicate the interpretation of in vitro results, highlighting the need to analyse this phenomenon in biomaterial testing.

Recent progress and treatment strategy of pectin polysaccharide based tissue engineering scaffolds in cancer therapy, wound healing and cartilage regeneration.

Natural polymers and its mixtures in the form of films, sponges and hydrogels are playing a major role in tissue engineering and regenerative medicine. Hydrogels have been extensively investigated as standalone materials for drug delivery purposes as they enable effective encapsulation and sustained release of drugs. Biopolymers are widely utilised in the fabrication of hydrogels due to their safety, biocompatibility, low toxicity, and regulated breakdown by human enzymes. Among all the biopolymers, polysaccharide-based polymer is well suited to overcome the limitations of traditional wound dressing materials. Pectin is a polysaccharide which can be extracted from different plant sources and is used in various pharmaceutical and biomedical applications including cartilage regeneration. Pectin itself cannot be employed as scaffolds for tissue engineering since it decomposes quickly. This article discusses recent research and developments on pectin polysaccharide, including its types, origins, applications, and potential demands for use in AI-mediated scaffolds. It also covers the materials-design process, strategy for implementation to material selection and fabrication methods for evaluation. Finally, we discuss unmet requirements and current obstacles in the development of optimal materials for wound healing and bone-tissue regeneration, as well as emerging strategies in the field.

Gypsum-Related Impact on Antibiotic-Loaded Composite Based on Highly Porous Hydroxyapatite-Advantages and Disadvantages.

Highly porous hydroxyapatite is sometimes considered toxic and useless as a biomaterial for bone tissue regeneration because of the high adsorption of calcium and phosphate ions from cell culture media. This negatively affects the osteoblast's growth in such ion-deprived media and suggests "false cytotoxicity" of tested hydroxyapatite. In our recent study, we showed that a small addition of calcium sulfate dihydrate (CSD) may compensate for this adsorption without a negative effect on other properties of hydroxyapatite-based biomaterials. This study was designed to verify whether such CSD-supplemented biomaterials may serve as antibiotic carriers. FTIR, roughness, mechanical strength analysis, drug release, hemocompatibility, cytotoxicity against human osteoblasts, and antibacterial activity were evaluated to characterize tested biomaterials. The results showed that the addition of 1.75% gypsum and gentamicin caused short-term calcium ion compensation in media incubated with the composite. The combination of both additives also increased antibacterial activity against bacteria representative of bone infections without affecting osteoblast proliferation, hemocompatibility, and mechanical parameters. Thus, gypsum and antibiotic supplementation may provide advanced functionality for bone-regeneration materials based on hydroxyapatite of a high surface area and increasingly high Ca2+ sorption capacity.

Selenium-Doped Mesoporous Bioactive Glass Regulates Macrophage Metabolism and Polarization by Scavenging ROS and Promotes Bone Regeneration In Vivo.

Bone regeneration is complex and involves multiple cells and systems, with macrophage-mediated immune regulation being critical for the development and regulation of inflammation, angiogenesis, and osteogenesis. Biomaterials with modified physical and chemical properties (e.g., modified wettability and morphology) effectively regulate macrophage polarization. This study proposes a novel approach to macrophage-polarization induction and -metabolism regulation through selenium (Se) doping. We synthesized Se-doped mesoporous bioactive glass (Se-MBG) and demonstrated its macrophage-polarization regulation toward M2 and its enhancement of the macrophage oxidative phosphorylation metabolism. The underlying mechanism is the effective scavenging of excessive intracellular reactive oxygen species (ROS) by the Se-MBG extracts through the promotion of peroxide-scavenging enzyme glutathione peroxidase 4 expression in the macrophages; this, in turn, improves the mitochondrial function. Printed Se-MBG scaffolds were implanted into rats with critical-sized skull defects to evaluate their immunomodulatory and bone regeneration capacity in vivo. The Se-MBG scaffolds demonstrated excellent immunomodulatory function and robust bone regeneration capacity. Macrophage depletion with clodronate liposomes impaired the Se-MBG-scaffold bone regeneration effect. Se-mediated immunomodulation, which targets ROS scavenging to regulate macrophage metabolic profiles and mitochondrial function, is a promising concept for future effective biomaterials for bone regeneration and immunomodulation.

Complementary Supramolecular Functionalization Enhances Antifouling Surfaces: A Ureidopyrimidinone-Functionalized Phosphorylcholine Polymer.

Fibrosis of implants remains a significant challenge in the use of biomedical devices and tissue engineering materials. Antifouling coatings, including synthetic zwitterionic coatings, have been developed to prevent fouling and cell adhesion to several implantable biomaterials. While many of these coatings need covalent attachment, a conceptually simpler approach is to use a spontaneous self-assembly event to anchor the coating to a surface. This could simplify material processing through highly specific molecular recognition. Herein, we investigate the ability to utilize directional supramolecular interactions to anchor an antifouling coating to a polymer surface containing a complementary supramolecular unit. A library of controlled copolymerization of ureidopyrimidinone methacrylate (UPyMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared and their UPy composition was assessed. The MPC-UPy copolymers were characterized by 1H NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC) and found to exhibit similar mol % of UPy as compared to feed ratios and low dispersities. The copolymers were then coated on an UPy elastomer and the surfaces were assessed for hydrophilicity, protein absorption, and cell adhesion. By challenging the coatings, we found that the antifouling properties of the MPC-UPy copolymers with more UPy mol % lasted longer than the MPC homopolymer or low UPy mol % copolymers. As a result, the bioantifouling nature could be tuned to exhibit spatio-temporal control, namely, the longevity of a coating increased with UPy composition. In addition, these coatings showed nontoxicity and biocompatibility, indicating their potential use in biomaterials as antifouling coatings. Surface modification employing supramolecular interactions provided an approach that merges the simplicity and scalability of nonspecific coating methodology with the specific anchoring capacity found when using conventional covalent grafting with longevity that could be engineered by the supramolecular composition itself.

Copper Ion-Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro-Vascularized Bone Regeneration.

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge and are often accompanied by the risk of infection. Thus, biomaterials with antibacterial and neurovascular regeneration properties are highly desirable. Here, a newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular regeneration and antibacterial agents, is designed. The copper ion modification process serves to improve the stability of the GeP nanosheets and offers a platform for the sustained release of bioactive ions. Study findings show that GelMA/GeP@Cu has effective antibacterial properties. The integrated hydrogel can significantly boost the osteogenic differentiation of bone marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial cells, and up-regulate neural differentiation-related proteins in neural stem cells in vitro. In vivo, in the rat calvarial bone defect mode, the GelMA/GeP@Cu hydrogel is found to enhance angiogenesis and neurogenesis, eventually contributing to bone regeneration. These findings indicate that in the field of bone tissue engineering, GelMA/GeP@Cu can serve as a valuable biomaterial for neuro-vascularized bone regeneration and infection prevention.

Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.

Cells are known to perceive their microenvironment through extracellular and intracellular mechanical signals. Upon sensing mechanical stimuli, cells can initiate various downstream signaling pathways that are vital to regulating proliferation, growth, and homeostasis. One such physiologic activity modulated by mechanical stimuli is osteogenic differentiation. The process of osteogenic mechanotransduction is regulated by numerous calcium ion channels-including channels coupled to cilia, mechanosensitive and voltage-sensitive channels, and channels associated with the endoplasmic reticulum. Evidence suggests these channels are implicated in osteogenic pathways such as the YAP/TAZ and canonical Wnt pathways. This review aims to describe the involvement of calcium channels in regulating osteogenic differentiation in response to mechanical loading and characterize the fashion in which those channels directly or indirectly mediate this process. The mechanotransduction pathway is a promising target for the development of regenerative materials for clinical applications due to its independence from exogenous growth factor supplementation. As such, also described are examples of osteogenic biomaterial strategies that involve the discussed calcium ion channels, calcium-dependent cellular structures, or calcium ion-regulating cellular features. Understanding the distinct ways calcium channels and signaling regulate these processes may uncover potential targets for advancing biomaterials with regenerative osteogenic capabilities.

Cyclodextrin regulated natural polysaccharide hydrogels for biomedical applications-a review.

Cyclodextrin and its derivative (CDs) are natural building blocks for linking with other components to afford functional biomaterials. Hydrogels are polymer network systems that can form hydrophilic three-dimensional network structures through different cross-linking methods and are developing as potential materials in biomedical applications. Natural polysaccharide hydrogels (NPHs) are widely adopted in biomedical field with good biocompatibility, biodegradability, low cytotoxicity, and versatility in emulating natural tissue properties. Compared with conventional NPHs, CD regulated natural polysaccharide hydrogels (CD-NPHs) maintain good biocompatibility, while improving poor mechanical qualities and unpredictable gelation times. Recently, there has been increasing and considerable usage of CD-NPHs while there is still no review comprehensively introducing their construction, classification, and application of these hydrogels from the material point of view regarding biomedical fields. To draw a complete picture of the current and future development of CD-NPHs, we systematically overview the classification of CD-NPHs, and provide a holistic view on the role of CD-NPHs in different biomedical fields, especially in drug delivery, wound dressing, cell encapsulation, and tissue engineering. Moreover, the current challenges and prospects of CD-NPHs are discussed rationally, providing an insight into developing vibrant fields of CD-NPHs-based biomedicine, and facilitating their translation from bench to clinical medicine.

Physicochemical and in vitro biological evaluation of an injectable self-healing quaternized chitosan/oxidized pectin hydrogel for potential use as a wound dressing material.

Injectable self-healing hydrogels are attractive materials for use as wound dressings. To prepare such hydrogels, the current study used quaternized chitosan (QCS) to improve the solubility and antibacterial activity and oxidized pectin (OPEC) to introduce aldehyde groups for Schiff's base reaction with the amine groups from QCS. Self-healing hydrogels were made by co-injection of polymer solutions at specific polymer concentrations and reagent ratios that optimized both Schiff's base reactions and ionic interactions. The optimal hydrogel displayed self-healing 30 min after cutting and continuous self-healing during continuous step strain analysis, rapid gelation (< 1 min), a storage modulus of 394 Pa, and hardness of 700 mN, and compressibility of 162 mN s. The adhesiveness of this hydrogel (133 Pa) was within a suitable range for application as a wound dressing. The extraction media from the hydrogel displayed no cytotoxicity to NCTC clone 929 cells and higher cell migration than the control. While the extraction media from the hydrogel was found not to have antibacterial properties, QCS was verified as having MIC50 of 0.04 mg/mL against both E. coli and S. aureus. Therefore, this injectable self-healing QCS/OPEC hydrogel has the potential use as a biocompatible hydrogel material for wound management.

A liquid metal-polydopamine composite for cell culture and electro-stimulation.

Gallium (Ga) is a low melting point metal in the liquid state in the biological environment which presents a unique combination of fluidity, softness, and metallic electrical and thermal properties. In this work, liquid Ga is proposed as a biocompatible electrode material for cell culture by electro-stimulation since the cytotoxicity of Ga is generally considered low and some Ga compounds have been reported to exhibit anti-bacterial and anti-inflammatory activities. Complementarily, polydopamine (PDA) was coated on liquid Ga to increase the attachment capability of cells on the liquid Ga electrode and provide enhanced biocompatibility. The liquid Ga layer could be readily painted at room temperature on a solid inert substrate, followed by the formation of a nanoscale PDA coating layer resulting in a conformable and biocompatible composite electrode. The PDA layer was shown to coordinate with Ga3+, which is sourced from liquid Ga, providing electrical conductivity in the cell culture medium. The PDA-Ga3+ composite acted as a conductive substrate for advanced electro-stimulation for cell culture methods of representative animal fibroblasts. The cell proliferation was observed to increase by ∼143% as compared to a standard glass coverslip at a low potential of 0.1 V of direct coupling stimulation. This novel PDA-Ga3+ composite has potential applications in cell culture and regenerative medicine.

Biomedical applications of chitosan/silk fibroin composites: A review.

Natural polymers have been used in the biomedical fields for decades, mainly derived from animals and plants with high similarities with biomacromolecules in the human body. As an alkaline polysaccharide, chitosan (CS) attracts much attention in tissue regeneration and drug delivery with favorable biocompatibility, biodegradation, and antibacterial activity. However, to overcome its mechanical properties and degradation behavior drawbacks, a robust fibrous protein-silk fibroin (SF) was introduced to prepare the CS/SF composites. Not only can CS be combined with SF via the amide and hydrogen bond formation, but also their functions are complementary and tunable with the blending ratio. To further improve the performances of CS/SF composites, natural (e.g., hyaluronic acid and collagen) and synthetic biopolymers (e.g., polyvinyl alcohol and hexanone) were incorporated. Also, the CS/SF composites acted as slow-release carriers for inorganic non-metals (e.g., hydroxyapatite and graphene) and metal particles (e.g., silver and magnesium), which could enhance cell functions, facilitate tissue healing, and inhibit bacterial growth. This review presents the state-of-the-art and future perspectives of different biomaterials combined with CS/SF composites as sponges, hydrogels, membranes, particles, and coatings. Emphasis is devoted to the biological potentialities of these hybrid systems, which look rather promising toward a multitude of applications.

Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials.

Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.

The influencing mechanism of phosphorus component on network structure and bioactivity of bioactive glass.

(64-x)SiO2-36CaO-xP2O5 (x = 0, 2, 4, 6, 8 mol%) bioactive glasses are successfully prepared by sol-gel method, and the effect of phosphorus (P) content on the network structure, phase composition and in vitro mineralization performance of bioactive glasses is investigated by the various characterization techniques. Results show that the as-prepared bioactive glass has the amorphous structure. With the increase of P content, it can be found in FT-IR spectra that the characteristic peaks of bending vibration corresponding to the P-O bond in PO43- gradually appear. Among, the typical 60S4P has the highest percentage (73.81%) of bridging oxygen (BO), indicating its highest aggregation degree of silicate network. Besides, the introduction of P2O5 results in the formation of monophosphate, which enable the bioactive glasses to dissolve rapidly in water or simulate body fluids (SBF) and crystallize to form hydroxyapatite (HA), thereby enhancing its biological activity. After soaking in SBF for 3 days, the irregular cauliflower-like HA particles appear on the surface of bioactive glass, and the appropriate amount of P addition in glass could result in its high bioactivity. Therefore, this study could provide a theoretical reference for the relationship between the network structure and bioactivity of bioactive glass.

Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.

The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials.

Recent advances in carbon dots: synthesis and applications in bone tissue engineering.

Bone tissue engineering (BTE), based on the perfect combination of seed cells, scaffold materials and growth factors, has shown unparalleled potential in the treatment of bone defects and related diseases. As the site of cell attachment, proliferation and differentiation, scaffolds composed of biomaterials play a crucial role in BTE. Over the past years, carbon dots (CDs), a new type of carbon-based nanomaterial, have attracted extensive research attention due to their good biocompatibility, unique optical properties, and abundant functional groups. This paper reviews recent research progress in the use of CDs in the field of BTE. Firstly, different preparation methods of CDs are summarized. Then, the properties and categories of CDs applied in BTE are described in detail. Subsequently, the applications of CDs in BTE, including osteogenesis, fluorescence tracing, phototherapy and antibacterial activity, are presented. Finally, the challenges and future perspectives of CDs in BTE are briefly discussed to give a comprehensive picture of CDs. This review provides a theoretical basis and advanced design strategies for the application of CDs in BTE.

Mechanistic crosstalk of extracellular calcium-mediated regulation of maturation and plasticity in human monocytes.

Innate immune cells play a pivotal role in controlling tissue repair and rejection after biomaterial implantation. Calcium supplementation regulates cellular responses and alter the pathophysiology of various diseases. A series of macrophage activations through differential plasticity has been observed after cell-to-material interactions. We investigated the role of calcium supplementation in controlling macrophage phenotypes in pro-inflammatory and pre-reparative states. Oxidative defence and mitochondria involvement in cellular plasticity and the sequential M0 to M1 and M1 to M2 transitions were observed after calcium supplementation. This study describes the molecular mechanism of reactive oxygen species and drives the interconnected cellular plasticity of macrophages in the presence of calcium. Gene expression, and immunostaining, revealed a relationship between MHC class II maturation and cellular plasticity. This study elucidated the role of controlled calcium supplementation under various conditions. These findings underscore the molecular mechanism of calcium-mediated immune induction and its favourable use in different calcium-containing biomaterials., essential for tissue regeneration.

In vitro cytocompatibility and antibacterial studies on biodegradable Zn alloys supplemented by a critical assessment of direct contact cytotoxicity assay.

In vitro cytotoxicity assessment is indispensable in developing new biodegradable implant materials. Zn, which demonstrates an ideal corrosion rate between Mg- and Fe-based alloys, has been reported to have excellent in vivo biocompatibility. Therefore, modifications aimed at improving Zn's mechanical properties should not degrade its biological response. As sufficient strength, ductility and corrosion behavior required of load-bearing implants has been obtained in plastically deformed Zn-3Ag-0.5Mg, the effect of simultaneous Ag and Mg additions on in vitro cytocompatibility and antibacterial properties was studied, in relation to Zn and Zn-3Ag. Direct cell culture on samples and indirect extract-based tests showed almost no significant differences between the tested Zn-based materials. The diluted extracts of Zn, Zn-3Ag, and Zn-3Ag-0.5Mg showed no cytotoxicity toward MG-63 cells at a concentration of ≤12.5%. The cytotoxic effect was observed only at high Zn2+ ion concentrations and when in direct contact with metallic samples. The highest LD50 (lethal dose killing 50% of cells) of 13.4 mg/L of Zn2+ ions were determined for the Zn-3Ag-0.5Mg. Similar antibacterial activity against Escherichia coli and Staphylococcus aureus was observed for Zn and Zn alloys, so the effect is attributed mainly to the released Zn2+ ions exhibiting bactericidal properties. Most importantly, our experiments indicated the limitations of water-soluble tetrazolium salt-based cytotoxicity assays for direct tests on Zn-based materials. The discrepancies between the WST-8 assay and SEM observations are attributed to the interference of Zn2+ ions with tetrazolium salt, therefore favoring its transformation into formazan, giving false cell viability quantitative results.

Black phosphorous-based biomaterials for bone defect regeneration: a systematic review and meta-analysis.

Critical-sized bone defects are always difficult to treat, and they are associated with a significant burden of disease in clinical practice. In recent decades, due to the fast development of biomaterials and tissue engineering, many bioinspired materials have been developed to treat large bone defects. Due to the excellent osteoblastic ability of black phosphorous (BP), many BP-based biomaterials have been developed to treat bone defects. Therefore, there are abundant studies as well as a tremendous amount of research data. It is urgent to conduct evidence-based research to translate these research data and results into validated scientific evidence. Therefore, in our present study, a qualitative systematic review and a quantitative meta-analysis were performed. Eighteen studies were included in a systematic review, while twelve studies were included in the meta-analysis. Our results showed that the overall quality of experimental methods and reports of biomaterials studies was still low, which needs to be improved in future studies. Besides, we also proved the excellent osteoblastic ability of BP-based biomaterials. But we did not find a significant effect of near-infrared (NIR) laser in BP-based biomaterials for treating bone defects. However, the quality of the evidence presented by included studies was very low. Therefore, to accelerate the clinical translation of BP-based biomaterials, it is urgent to improve the quality of the study method and reporting in future animal studies. More evidence-based studies should be conducted to enhance the quality and clinical translation of BP-based biomaterials.