Guided Bone Regeneration Using Barrier Membrane in Dental Applications.

Guided bone regeneration (GBR) is a widely used technique in preclinical and clinical studies due to its predictability. Its main purpose is to prevent the migration of soft tissue into the osseous wound space, while allowing osseous cells to migrate to the site. GBR is classified into two main categories: resorbable and non-resorbable membranes. Resorbable membranes do not require a second surgery but tend to have a short resorption period. Conversely, non-resorbable membranes maintain their mechanical strength and prevent collapse. However, they require removal and are susceptible to membrane exposure. GBR is often used with bone substitute graft materials to fill the defect space and protect the bone graft. The membrane can also undergo various modifications, such as surface modification and biological factor loading, to improve barrier functions and bone regeneration. In addition, bone regeneration is largely related to osteoimmunology, a new field that focuses on the interactions between bone and the immune system. Understanding these interactions can help in developing new treatments for bone diseases and injuries. Overall, GBR has the potential to be a powerful tool in promoting bone regeneration. Further research in this area could lead to advancements in the field of bone healing. This review will highlight resorbable and non-resorbable membranes with cellular responses during bone regeneration, provide insights into immunological response during bone remodeling, and discuss antibacterial features.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Blending with transition metals improves bioresorbable zinc as better medical implants.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Cellular mechanisms of biodegradable zinc and magnesium materials on promoting angiogenesis.

Biodegradable metals, zinc and magnesium, have been regarded as next-generation, biomedical implant materials to promote tissue repair and regeneration. These implants might also promote the vascularization of surrounding neotissue. Released metallic ions, Zn2+ and Mg2+, show promise in vitro to implement vessel growth by stimulating the expression of pro-angiogenic cytokines, yet there is little known regarding how cellular responses transcend to influence the tissue environment. This study serves to optimize angiogenic behavior using EA.hy926 endothelial cultures exposed to Zn2+ and Mg2+ gradients and observe the translation of these effects on blood vessel development via the in ovo chorioallantoic membrane (CAM) assay. Findings indicate that Zn2+ 10 µM and Mg2+ 10 mM instigate the most prominent effects using endothelial cultures via scratch wound and tube formation assays, yet higher concentrations at Zn2+ 50 µM and Mg2+ 50 mM encourage significant angiogenesis along the CAM. Immunoblotting results also conclude the presence and upregulation of cytokines involved in vessel growth. Optimizing the angiogenic potential of Zn2+ and Mg2+ separately sheds light to design future engineering constructs for promoting blood vessel development and successful assimilation between host and implant tissue.

Integrated Analysis and Identification of CSF-Derived Risk miRNAs and Pivotal Genes in Multiple Sclerosis.

Multiple sclerosis (MS) is a common chronic autoimmune disorder of the central nervous system that predominantly affects young adults. Mounting evidence indicates that deregulation of microRNAs (miRNAs) in cerebrospinal fluid (CSF) has been implicated in MS as a potential biomarker. However, comprehensive assessments of CSF miRNAs and their target genes are lacking. Here, aberrantly expressed CSF miRNAs of MS patients were obtained from numerous studies by manual search. With detailed information on these miRNAs, we utilized online databases to screen out immune-related target genes and further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. To identify MS high-risk pathways and pivotal genes, pathway crosstalk and pathway-gene networks were constructed, followed by the establishment of a protein-protein interaction (PPI) network. The datasets collected from ArrayExpress were used to assess pivotal genes. Overall, 21 MS-related CSF miRNAs were included in this study. Subsequently, we identified 469 MS-related genes and 14 high-risk pathways. In the pathway-gene network, 27 critical MS-related genes participated in at least half of the high-risk pathways, and these genes were used to identify pivotal genes. Finally, miR-150, miR-328, and miR-34c-5p were determined to be risk miRNAs via the regulation of the pivotal risk genes MAPK1, AKT1, and VEGFA. Among them, VEGFA was validated to be significantly decreased in the CSF cells of MS patients by transcriptomic datasets. These findings may provide potential biomarkers or therapeutic targets and help elucidate the molecular mechanisms underlying the pathogenesis of MS.

Improved mechanical, degradation, and biological performances of Zn-Fe alloys as bioresorbable implants.

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn-Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn-Fe alloys showed outstanding antibacterial property. Taken together, Zn-Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.

Toward a Better Regeneration through Implant-Mediated Immunomodulation: Harnessing the Immune Responses.

Tissue repair/regeneration, after implantation or injury, involves comprehensive physiological processes wherein immune responses play a crucial role to enable tissue restoration, amidst the immune cells early-stage response to tissue damages. These cells break down extracellular matrix, clear debris, and secret cytokines to orchestrate regeneration. However, the immune response can also lead to abnormal tissue healing or scar formation if not well directed. This review first introduces the general immune response post injury, with focus on the major immune cells including neutrophils, macrophages, and T cells. Next, a variety of implant-mediated immunomodulation strategies to regulate immune response through physical, chemical, and biological cues are discussed. At last, various scaffold-facilitated regenerations of different tissue types, such as, bone, cartilage, blood vessel, and nerve system, by harnessing the immunomodulation are presented. Therefore, the most recent data in biomaterials and immunomodulation is presented here in a bid to shape expert perspectives, inspire researchers to go in new directions, and drive development of future strategies focusing on targeted, sequential, and dynamic immunomodulation elicited by implants.

Calcium phosphate coatings enhance biocompatibility and degradation resistance of magnesium alloy: Correlating in vitro and in vivo studies.

Magnesium (Mg) and its alloys are promising biodegradable materials for orthopedic applications. However, one of the major problems is their rapid degradation rate with quick evolution of hydrogen gas. To overcome this problem, calcium phosphate (CaP) coatings have been used to improve the degradation resistance and the biocompatibility of Mg materials. This study focuses on the comparison and correlation of the in vitro and in vivo degradation and biocompatibility behaviors of these materials. A CaP coating consisting of dicalcium phosphate dihydrate (DCPD) was deposited on an AZ60 Mg alloy by the chemical conversion method. Then, the in vitro degradation testing including electrochemical and immersion tests, and in vivo implantation of the CaP coated Mg alloy were conducted to compare the degradation behaviors. Next, the in vitro cell behavior and in vivo bone tissue response were also compared on both uncoated and CaP-coated Mg samples. Data showed that the CaP coating provided the Mg alloy with significantly better biodegradation behavior and biocompatibility. The in vitro and in vivo biocompatibility tests exhibited good consistency while not the case for biodegradation. Results showed that the in vitro electrochemical test could be a quick screening tool for the biodegradation rate, while the in vitro immersion degradation rate was often 2-4 folds faster than the in vivo degradation rate.

A multifunctional polypyrrole/zinc oxide composite coating on biodegradable magnesium alloys for orthopedic implants.

Magnesium (Mg) and its alloys exhibit great potential in clinical applications owing to the outstanding biological performance and excellent mechanical properties, whereas the quick corrosion rate in the physiological environment has limited their further clinical application. In this work, we designed and developed a multifunctional polypyrrole/zinc oxide (Ppy/ZnO) composite coating by cyclic voltammetry method, aiming to enhance the biocorrosion resistance, biocompatibility and antibacterial property of the Mg alloys. The electrochemical and immersion tests indicated that the corrosion resistance of the Mg alloy was improved significantly by the composite coating. A systematic in vitro investigation of cellular response confirmed that the composite coating significantly promoted the adhesion and proliferation of cells. In addition, the composite coating showed a remarkable antibacterial ability of 96.5 ±â€¯2.6 % against Escherichia coli (E.coli). The enhanced corrosion resistance, cytocompatibility, and antibacterial property of the Ppy/ZnO coated Mg alloy makes it a promising candidate as orthopedic implants material.

Micro-/Nanotopography on Bioresorbable Zinc Dictates Cytocompatibility, Bone Cell Differentiation, and Macrophage Polarization.

Bioresorbable metals are quickly advancing in the field of regenerative medicine for their promises of tissue restoration without adverse consequences from their lifelong presence. Zn has recently risen to the top of bioresorbable metals with great potential as a medical implant. However, cell adhesion and colonization on the Zn substrate surface remains challenging, which could damper interfacial tissue-implant integration. Inspired by the fact that surface topography can regulate cell function and fate, we hypothesize that topography on bioresorbable Zn can dictate material biocompatibility, cell differentiation, and immunomodulation. To verify this, surface-engineered Zn plates with nano-, submicro-, and microtopographies were systematically investigated. The microscale topography exhibited increased adhesion, pronounced self-renewal, and enhanced osteogenic differentiation of bone cells as well as less macrophage inflammatory polarization, reduced platelet adhesion, and better hemocompatibility. Thus, surface topography could be a viable strategy to enhance bioresorbable Zn's biocompatibility and integration with surrounding tissues while reducing inflammation.

Porous zinc scaffolds for bone tissue engineering applications: A novel additive manufacturing and casting approach.

As a degradable metal, zinc (Zn) has attracted an immense amount of interest as the next generation of bioresorbable implants thanks to its modest corrosion rate and its vital role in bone remodeling, yet very few studies have thoroughly investigated its functionality as a porous implant for bone tissue engineering purposes. Zn bone scaffolds with two different pore sizes of 900 µm and 2 mm were fabricated using additive manufacturing-produced templates combined with casting. The compressive properties, corrosion rates, biocompatibility, and antibacterial performance of the bioscaffolds were examined and compared to a non-porous control. The resulting textured and porous Zn scaffolds exhibit a fully interconnected pore structure with precise control over topology. As pore size and porosity increased, mechanical strength decreased, and corrosion rate accelerated. Cell adhesion and growth on scaffolds were enhanced after an ex vivo pretreatment method. In vitro cellular tests confirmed good biocompatibility of the scaffolds. As porosity increased, potent antibacterial rates were also observed. Taken together, these results demonstrate that Zn porous bone scaffolds are promising for orthopedic applications.

Salt Preform Texturing of Absorbable Zn Substrates for Bone-implant Applications.

Surface roughness is an important factor in improving the bone-implant contact area to enhance bone regeneration, yet this aspect has not been applied to absorbable metals. Textured zinc surfaces with varying degrees of surface roughness were produced using a salt-preform method with fine- and coarse-grained salts and compared to a polished control sample. The resulting surfaces were characterized by scanning electron microscopy (SEM), surface roughness, corrosion rates, and in vitro cytotoxicity. The resulting textured surfaces exhibit micron-sized cavities and increased roughness consistent with the initial salt particle size. The corrosion rate was shown to accelerate significantly as compared to the polished control sample, and pre-osteoblasts displayed healthy morphologies on the textures. The results confirm textured zinc surfaces support cell adhesion and can be used to control the corrosion rate. This study represents an important intermediate step that can be applied to porous absorbable metal scaffolds for bone-implant applications.

Evolution of metallic cardiovascular stent materials: A comparative study among stainless steel, magnesium and zinc.

A cardiovascular stent is a small mesh tube that expands a narrowed or blocked coronary artery. Unfortunately, current stents, regardless metallic or polymeric, still largely fall short to the ideal clinical needs due to late restenosis, thrombosis and other clinical complications. Nonetheless, metallic stents are preferred clinically thanks to their superior mechanical property and radiopacity to their polymeric counterparts. The emergence of bioresorbable metals opens a window for better stent materials as they may have the potential to reduce or eliminate late restenosis and thrombosis. In fact, some bioresorbable magnesium (Mg)-based stents have obtained regulatory approval or under trials with mixed clinical outcomes. Some major issues with Mg include the too rapid degradation rate and late restenosis. To mitigate these problems, bioresorbable zinc (Zn)-based stent materials are being developed lately with the more suitable degradation rate and better biocompatibility. The past decades have witnessed the unprecedented evolution of metallic stent materials from first generation represented by stainless steel (SS), to second generation represented by Mg, and to third generation represented by Zn. To further elucidate their pros and cons as metallic stent materials, we systematically evaluated their performances in vitro and in vivo through direct side-by-side comparisons. Our results demonstrated that tailored Zn-based material with proper configurations could be a promising candidate for a better stent material in the future.

Bioactive glass coatings on metallic implants for biomedical applications.

Metallic implant materials possess adequate mechanical properties such as strength, elastic modulus, and ductility for long term support and stability in vivo. Traditional metallic biomaterials, including stainless steels, cobalt-chromium alloys, and titanium and its alloys, have been the gold standards for load-bearing implant materials in hard tissue applications in the past decades. Biodegradable metals including iron, magnesium, and zinc have also emerged as novel biodegradable implant materials with different in vivo degradation rates. However, they do not possess good bioactivity and other biological functions. Bioactive glasses have been widely used as coating materials on the metallic implants to improve their integration with the host tissue and overall biological performances. The present review provides a detailed overview of the benefits and issues of metal alloys when used as biomedical implants and how they are improved by bioactive glass-based coatings for biomedical applications.

Combined Tribological and Bactericidal Effect of Nanodiamonds as a Potential Lubricant for Artificial Joints.

The artificial joints, for example, knee and hip implants, are widely used for the treatment of degenerative joint diseases and trauma. The current most common material choice for clinically used implants is the combination of polymer-on-metal structures. Unfortunately, these joints often suffer from high friction and wear, leading to associated inflammation and infection and ultimate failure of the artificial joints. Here, we propose an alternative solution to this tribologically induced failure of the joint materials. We demonstrate that the friction and wear behavior of ultrahigh-molecular-weight polyethylene (UHMWPE) and titanium tribopair, used to mimic the artificial joint interface, can be improved by introducing nanodiamond (ND) particles in the sliding contact. Characterization of the wear track using energy-dispersive spectroscopy and Raman spectroscopy revealed that the tribofilm formed from embedded NDs during sliding significantly suppressed the wear of the UHMWPE surface. In addition to the improved lubrication characteristics, NDs exhibit high biocompatibility with the bone cells and promising antibacterial properties against Staphylococcus aureus, the most common strain associated with artificial joint infection. These results indicate that NDs can be used as a promising nontoxic human-body lubricant with antiwear and antibacterial features, thus demonstrating their great potential to treat artificial joint complications through intra-articular injection.

Interfacial Zinc Phosphate is the Key to Controlling Biocompatibility of Metallic Zinc Implants.

Recently emerged metallic zinc (Zn) is a new generation of promising candidates for bioresorbable medical implants thanks to its essential physiological relevance, mechanical strength, and more matched degradation pace to that of tissue healing. Zn-based metals exhibit excellent biocompatibility in various animal models. However, direct culture of cells on Zn metals yields surprisingly low viability, indicating high cytotoxicity of Zn. This contradicting phenomenon should result from the different degradation mechanisms between in vitro and in vivo. To solve this puzzle, the roles of all major players, i.e., zinc phosphate (ZnP), zinc oxide (ZnO), zinc hydroxide (Zn(OH)2), pH, and Zn2+, which are involved in the degradation process are examined. Data shows that ZnP, not ZnO or Zn(OH)2, significantly enhances its biocompatibility. The mild pH change during degradation also has no significant impact on cell viability. Collectively, ZnP appears to be the key to controlling the biocompatibility of Zn implants and could be applied as a novel surface coating to improve biocompatibility of different implants.

The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article.

BACKGROUND: Magnesium (Mg) is an essential element for the body. It is a cofactor for ATP, DNA, and RNA and more than 600 enzymes. As it is similar to Ca2+, this element can also act as a cell signaling molecule and play multiple important roles in the nervous, muscle, and immune systems. Recent studies have associated Mg-deficiency with many neurological disorders, such as cerebral vasospasm, Alzheimer's disease, stroke, and migraine. As it plays such a crucial role in human body, therefore, we summarized the role of Mg in neurological disorders to illustrate the symptoms caused by Mg-deficiency and the possible underlying mechanisms. METHODS: We critically discuss the role of it that we review the recent literature of magnesium. We also review the available data which are concerning the role of magnesium in neurological disorders. RESULTS: Magnesium is related to neurological disorders on the basis of the study of animals and humans experiments. Furthermore, these nervous systems related diseases include cerebral vasospasm, Alzheimer's disease, Parkinson's disease, stroke and migraine. CONCLUSION: Magnesium has effects on neurological disorders, such as its utility in cerebral vasospasm, Alzheimer's disease, Parkinson's disease, stroke and migraine. So here we make a brief review to conclude it.

Biofunctionalization of metallic implants by calcium phosphate coatings.

Metallic materials have been extensively applied in clinical practice due to their unique mechanical properties and durability. Recent years have witnessed broad interests and advances on surface functionalization of metallic implants for high-performance biofunctions. Calcium phosphates (CaPs) are the major inorganic component of bone tissues, and thus owning inherent biocompatibility and osseointegration properties. As such, they have been widely used in clinical orthopedics and dentistry. The new emergence of surface functionalization on metallic implants with CaP coatings shows promise for a combination of mechanical properties from metals and various biofunctions from CaPs. This review provides a brief summary of state-of-art of surface biofunctionalization on implantable metals by CaP coatings. We first glance over different types of CaPs with their coating methods and in vitro and in vivo performances, and then give insight into the representative biofunctions, i.e. osteointegration, corrosion resistance and biodegradation control, and antibacterial property, provided by CaP coatings for metallic implant materials.

Enhanced cytocompatibility and antibacterial property of zinc phosphate coating on biodegradable zinc materials.

Zinc (Zn) has recently emerged as a promising biodegradable metal thanks to its critical physiological roles and promising degradation behavior. However, cytocompatibility and antibacterial property of Zn is still suboptimal, in part, due to the excessive Zn ions released during degradation. Inspired by the calcium phosphate-based minerals in natural bone tissue, zinc phosphate (ZnP) coatings were prepared on pure Zn using a chemical conversion method in this study. The coating morphology was then optimized through controlling the pH of coating solution, resulting in a homogeneous micro-/nano-ZnP coating structure. The ZnP coating significantly increased the cell viability, adhesion, and differentiation of pre-osteoblasts and vascular endothelial cells, while significantly reduced the adhesion of the platelets and E. coli. Additionally, ZnP coating significantly reduced the Zn ion release from the bulk material during degradation process, resulting in a much lower Zn2+ concentration and pH change in the surrounding environment. The improved hemocompatibility, cytocompatibility and antibacterial performance of ZnP coated Zn biomaterials could be mainly attributed to the controlled Zn ion release and micro-/nano-scaled coating structure. Taken together, ZnP coating on Zn-based biomaterial appears to be a viable approach to enhance its biocompatibility and antibacterial property as well as to control its degradation rate. Statement of Significance Zn and its alloys are promising biodegradable implant materials for orthopedic and cardiovascular applications. However, notable cytotoxicity has been reported due to degradation products accumulated in the local environment, largely overdosed Zn2+. Thus, controlling burst Zn2+ release is the key to minimize the toxicity of Zn implants. To achieve this goal, we prepared a homogenous ZnP coating on Zn metals thanks to its easy synthesis, stable chemical property, and good biocompatibility. Results showed that ZnP not only improved the cell viability, adhesion and proliferation, but also significantly reduced the attachment of platelet and bacterial. Therefore, ZnP could be a promising approach to improve the functional performance of Zn-based implants, and potentially be applied to many other medical implants.

Mechanical Strength, Biodegradation, and in Vitro and in Vivo Biocompatibility of Zn Biomaterials.

Zn-based biomaterials have emerged as promising new types of bioresorbable metallics applicable to orthopedic devices, cardiovascular stents, and other medical applications recently. Compared to other degradable metallic biomaterials (i.e., Mg- or Fe-based), Zn biomaterials have a more appropriate corrosion rate without hydrogen gas evolution. Here, we evaluated the potential of Zn-based metallics as medical implants, both in vitro and in vivo, alongside a standard benchmark Mg alloy, AZ31. The mechanical properties of the pure Zn were not strong enough but were significantly enhanced (microhardness > 70 kg/mm2, strength > 220 MPa, elongation > 15%) after alloying with Sr or Mg (1.5 at. %), surpassing the minimal design criteria for load-bearing device applications. The corrosion rate of Zn-based biomaterials was about 0.4 mm/year, significantly slower than that of AZ31. The measured cell viability and proliferation of three different human primary cells fared better for Zn-based biomaterials than AZ31 using both direct and indirect culture methods. Platelet adhesion and activation on Zn-based materials were minimal, significantly less than on AZ31. The hemolysis ratio of red cells (<0.5%) after incubation with Zn-based materials was also well below the ISO standard of 5%. Moreover, Zn-based biomaterials promoted stem cell differentiation to induce the extracellular matrix mineralization process. In addition, in vivo animal testing using subcutaneous, bone, and vascular implantations revealed that the acute toxicity and immune response of Zn-based biomaterials were minimal/moderate, comparable to that of AZ31. No extensive cell death and foreign body reactions were observed. Taken together, Zn-based biomaterials may have a great potential as promising candidates for medical implants.